Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation.

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.

Development and validation of a risk prediction model for breast cancer-related lymphedema in postoperative patients with breast cancer.

OBJECTIVE: Breast cancer-related lymphedema (BCRL) is a common post-operative complication in patients with breast cancer. Here, we sought to develop and validate a predictive model of BCRL in Chinese patients with breast cancer. METHODS: Clinical and demographic data on patients with breast cancer were collected between 2016 and 2021 at a Cancer Hospital in China. A nomogram for predicting the risk of lymphedema in postoperative patients with breast cancer was constructed and verified using R 3.5.2 software. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics, and the model was internally validated. RESULTS: A total of 1732 postoperative patients with breast cancer, comprising 1212 and 520 patients in the development and validation groups, respectively, were included. Of these 438 (25.39%) developed lymphedema. Significant predictors identified in the predictive model were time since breast cancer surgery, level of lymph node dissection, number of lymph nodes dissected, radiotherapy, and postoperative body mass index. At the 31.9% optimal cut-off the model had AUC values of 0.728 and 0.710 in the development and validation groups, respectively. Calibration plots showed a good match between predicted and observed rates. In decision curve analysis, the net benefit of the model was better between threshold probabilities of 10%-80%. CONCLUSION: The model has good discrimination and accuracy for lymphedema risk assessment, which can provide a reference for individualized clinical prediction of the risk of BCRL. Multicenter prospective trials are required to verify the predictive value of the model.

[Scoping review of rapid health technology assessment].

This study aims to summarize the research on rapid health technology assessment(RHTA) based on scoping review, which is expected to serve as a reference for future research on RHTA. First, articles on RHTA were retrieved from both Chinese and English databases. After data screening and extraction by two personnel independently, descriptive analysis was conducted on the results, and evidence distribution was analyzed based on tables, bar charts, line charts, radar charts, and pie charts. Finally, a total of 82 eligible articles were included and the characteristics were as follows.(1) Articles on RHTA were mainly published from 2011 to 2022. The number of articles showed an obvious increase from 2014 and surged in 2019.(2) Among the journals with the above RHTA papers published, Chinese Journal of New Drugs(21.5%), Evaluation and Analysis of Drug-Use in Hospitals of China(16.9%), and Chinese Pharmacy(15.4%) topped the Chinese journals in the number of the papers, while International Journal of Technology Assessment in Health Care(23.5%), Reviews in Medical Virology(11.8%), and Value in Health(11.8%) came out on top in the English journals.(3)The RHTA of drugs(especially western medicine)(68.7%) dominated the eligible articles, followed by the RHTA of therapy technology(13.1%), detection technology(5.1%), and diagnosis technology(1.0%). There was a significant gap in the number of studies among different health technology categories and an imbalance in the types of health technologies involved in the overall RHTA studies.(4) RHTA of tumors has been the research focus in recent years. In summary, RHTA plays a positive role in rapid health decision-making, but there is a lack of primary data sources at present. Compared with the systematic review, Meta-analysis, and pharmacoeconomic studies, a few reports on health technology assessment(HTA) were included. In the future, research on the evaluation of the safety, efficacy, cost effectiveness and social applicability of health technologies should be further strengthened.

Anti-inflammatory Dimeric Benzophenones from an Endophytic Pleosporales Species.

Eight new polyketides, including three dimeric benzophenones, named dipleosporones A-C (1-3), three benzophenones (4-6), one xanthone (7), and one phenylbenzoate (8), along with seven known polyketides (9-15) were isolated from the fungus Pleosporales sp. YY-4. The structures of the new compounds were established on the basis of spectroscopic methods, including high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance. This is the first report of a benzophenone dimer connection via a C bridge from natural sources. An anti-inflammatory assay indicated that the dimeric benzophenones (1-3) inhibited lipopolysaccharide-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values ranging from 8.8 to 18.1 µM, being more potent than the positive control, dexamethasone (IC50 = 22.2 µM).

Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in a time and dose-dependent manner. All the results suggest that the indoline derivatives may be a class of novel tubulin inhibitors with potential anticancer activity, and which is worthy of further study.

WITHDRAWN: Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of ß-tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in time and dose-dependent manners. All the results suggest that the indoline derivatives might be a class of novel tubulin inhibitors with potential anticancer activity and is worthy of further study.

Risk factors of postoperative adhesive bowel obstruction in children with complicated appendicitis.

PURPOSE: Postoperative adhesive bowel obstruction (ABO) is a common complication especially in complicated appendicitis. This study aimed to analyze the risk factors for ABO following appendectomy in children with complicated appendicitis, and establish a scoring model for predicting postoperative ABO and treatment option to relieve the obstruction. METHODS: From December 2014 to January 2020, all files of consecutive patients with complicated appendicitis underwent appendectomy were reviewed. Univariate and multivariate analyses were used to screen out the risk factors of postoperative ABO, and establish a scoring model for predicting postoperative ABO and surgical relief to relieve the obstruction. RESULTS: Of the 780 patients, 87 (11.2%) had ABO following appendectomy, including 27 who underwent surgical relief. Age ≤ 6 years, overweight and obesity, duration of symptoms ≥ 36 h, C-reactive protein ≥ 99 mg/L, duration of operation ≥ 60 min, intraoperative peritoneal lavage, and postoperative flatus time ≥ 20 h were independent risk factors for postoperative ABO. The final scoring model for postoperative ABO included factors above, and exhibited a high degree of discrimination (area under the curve [AUC]: 0.937; 95% confidence interval [CI] 0.913-0.960) corresponding to an optimal cut-off value of 6: 82.8% sensitivity, 92.6% specificity. Furthermore, the scoring model showed a sensitivity of 74.1% and a specificity of 91.7% for patients wo underwent surgical relief to relieve obstruction with the optimal cut-off value of 9. CONCLUSION: Risk factors for postoperative ABO should be taken seriously in children with complicated appendicitis. The scoring model is a novel but promising method to predict postoperative ABO and provide reference for clinical decision-making to relieve the obstruction.

Effect mechanism of copper ions on photocatalytic activity of TiO2/graphene oxide composites for phenol-4-sulfonic acid photodegradation.

Organic pollutants in electroplating wastewater can be removed by photodegradation, however the effect mechanism of heavy metal ions on photocatalytic activity still remains unknown. Herein, we firstly reported the self-assembly synthesis of titanium dioxide/reduced graphene oxide (TiO2/rGO) composites for phenol-4-sulfonic acid (PSA) removal, and investigated the effects of Cu2+ ions on photocatalytic efficiency. During the self-assemble process, rGO nanosheets were connected together to form network macropores, and simultaneously induced the deposition of hierarchically nanostructured TiO2 microspheres. The synergetic effects of TiO2 microspheres and rGO nanosheets improved the photocatalytic activity by enhancing light adsorption ability, stabilizing electron-hole separation and decreasing band gap energy. The Cu2+ ions in wastewater showed positive and negative effects on PSA photodegradation. In the photocatalytic reaction, the electron-induced reduction reaction of Cu(II) into Cu(0) or Cu(I) took place, which inhibited electron-hole recombination and thus enhanced photocatalytic activity. However, the high chemical stability of PSA-Cu(II) complex compounds held back PSA photodegradation. The appropriate concentrations of Cu2+ ions at around 25 mg/L accelerated PSA photodegradation over TiO2/rGO composites. The PSA degradation into CO2 and H2O was performed by using hydroquinone, benzoquinone and maleic acid as degradation intermediates. Hence, TiO2/rGO composites are novel multifunctional photocatalysts to purify electroplating wastewater.

Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence.

PURPOSE: The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence. MATERIALS AND METHODS: We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results. RESULTS: Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein-protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. CONCLUSION: In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.

HSF1/AMPKα2 mediated alteration of metabolic phenotypes confers increased oxaliplatin resistance in HCC cells.

Recent studies suggest that up-regulated HSF1 possesses metabolic phenotypes switch and chemoresistance in cancer cells. However, the mechanism in which these characteristics are still ambiguous. Our study aims to identify how HSF1 confers chemoresistance through regulating metabolic pathway in hepatocellular carcinoma (HCC). Oxaliplatin (OXA)-resistant HCC cells (HCC-OXR) in both of abundant glucose (AG; 25 mM) and low glucose (LG; 5.5 mM) conditions were constructed; then glucose consumption, lactate production, intracellular ATP level and oxygen consumption of parental and OXA-resistant cells were determined by using the associated detected kits. Moreover, HSF1 was knocked down to analyze its effects on metabolic phenotypes alteration and chemoresistance formation in HCC cells. Compared to cells in AG condition, HCC cells delayed to form chemoresistance to OXA in LG condition; and OXA-resistant cells underwent a metabolic switch from glycolysis to oxidative phosphorylation (OXPHOS), which presented decreased glucose uptake and lactate production with increased levels of oxygen consumption and intercellular ATP; interestingly, this energy-producing pathway was blocked in HSF1-knockdown OXA-resistant cells, especially in LG condition. Analysis on previous data revealed that AMPK pathway was a critical regulator in the metabolism of OXA-resistance HCC cells. Furthermore, AMPKα2 was identified as an important factor regulated by HSF1 to achieve metabolic phenotype switch in OXA-resistance HCC cells. Consequently, these results suggest that combining restrictive glucose uptake and targeting HSF1/AMPKα2 is an attractive strategy to prevent chemoresistance to OXA in HCC patients.

LncRNA-MALAT1 promotes tumorogenesis of infantile hemangioma by competitively binding miR-424 to stimulate MEKK3/NF-κB pathway.

AIMS: Infantile hemangioma (IH) is the most common vascular neoplasm in infant and young children. Long non-coding RNAs (lncRNAs) are known to be associated with IH. This study aims to investigate the role and underlying mechanism of lncRNA-MALAT1 in IH. MAIN METHODS: qRT-PCR was used to quantify the expressions of MALAT1, miR-424, and MEKK3 in IH tissues. The cell proliferation, apoptosis, migration, invasion, and tube formation ability were assessed by MTT assay, colony formation assay, flow cytometric analysis, transwell assay and tube formation assay, respectively. The interaction among MALAT1, miR-424 and MEKK3 was evaluated by luciferase reporter assay. Immunohistochemistry (IHC) and Western blotting were utilized to evaluate the expression levels of MEKK3, Ki-67 and NF-κB pathway-related proteins both in vitro and in vivo. KEY FINDINGS: In IH tissues, MALAT1 and MEKK3 were overexpressed while miR-424 was down-regulated. Silencing MALAT1 or overexpression of miR-424 significantly inhibited the IH cell proliferation, migration and tube formation, but promoted the cell apoptosis. Knockdown of MALAT1 suppressed the expression of MEKK3 and inactivated the IKK/NF-κB pathway by sponging miR-424. Overexpression of MEKK3 in HemEcs reversed the impact of knockdown of MALAT1 and overexpression of miR-424 on the cell proliferation, apoptosis, migration, invasion and tube formation rate. The tumor xenografts experiments demonstrated that silencing MALAT1 significantly inhibited the tumor growth in vivo and Ki-67 in the tumor tissues was also significantly suppressed. SIGNIFICANCE: MALAT1 promoted the IH progression through inhibiting miR-424 to activate MEKK3-mediated IKK/NF-κB pathway, suggesting that MALAT1, miR-424 and MEKK3 could be used as potential targets to improve IH treatment efficiency.

HSF1: a mediator in metabolic alteration of hepatocellular carcinoma cells in cross-talking with tumor-associated macrophages.

Recently, heat shock transcription factor 1 (HSF1) is observed to be involved in the process of cellular metabolism in cancer. However, the roles of HSF1 in the metabolic alteration of hepatocellular carcinoma (HCC) in tumor microenvironment remain elusive. Here, HCC cells were co-cultured with tumor-associated macrophages (TAM). The levels of glucose uptake, the lactate release, reactive oxygen species (ROS) and mtDNA content were measured by the associated Kits; all detected protocols were correspondingly according to the manufacturers' instructions. Recombinant lentiviruses with shRNA against HSF1 and MCT4 were transfected into HCC cells or TAMs. Western blot analysis was conducted to detect the relative levels of HSF1, MCT1 and MCT4 proteins. CCK-8 assay was utilized to assess cell proliferation. Based on the co-culture system with HCC cells and TAMs, metabolic alteration of HCC cells after co-culture with TAMs was observed. Furthermore, glucose consumption rate, lactate production rate and intercellular ROS level were decreased, while the copy number of mtDNA was increased in HSF1-knockdown HCC cells. Besides, metabolic crosstalk between HCC cells and TAMs was induced by HSF1 not only in HCC cells but also in TAMs through regulating individually MCT1 and MCT4 expressions. To the best of our knowledge, this is an important study to demonstrate the roles of HSF1 in regulating metabolic alteration of HCC cells induced by TAMs, which implies the potential use of HSF1 as a target modulating malignant behaviors of HCC cells.

Probiotic strategies to prevent necrotizing enterocolitis in preterm infants: a meta-analysis.

PURPOSE: We aimed to compare probiotics with placebo for necrotizing enterocolitis in preterm infants and to evaluate the safety and effect and strict effect of specific probiotic genera. METHODS: Data recorded until January 2019 were searched, and relevant academic articles from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were selected by two independent reviewers. Two reviewers independently included randomized controlled trials that compared probiotics and placebo in preterm infants. The outcomes included more than one of the following outcomes: incidence of necrotizing enterocolitis, necrotizing enterocolitis-related mortality, incidence of sepsis, and all-cause mortality. Two reviewers independently extracted data and assessed the risk of bias and quality of evidence. RESULTS: We identified 34 eligible studies of 9161 participants. This meta-analysis showed an overall advantage of probiotics to prevent the incidence of necrotizing enterocolitis (3.54%) and gut-associated sepsis (15.59%), and decrease mortality (5.23%) in preterm infants. A probiotic mixture showed a huge advantage and vitality in preventing necrotizing enterocolitis (2.48%) and gut-associated sepsis (18.39%), and in reducing mortality (5.57%) in preterm infants. CONCLUSION: The probiotic mixture showed advantages over the single strains to decrease the incidences of necrotizing enterocolitis and gut-associated sepsis, and mortality in preterm infants.

Retrospective study on the outcomes of infantile tufted angioma complicated by Kasabach-Merritt Phenomenon.

OBJECTIVE: To analyze the clinical characteristics and treatment of pediatric tufted angiomas(TA)complicated by Kasabach-Merritt Phenomenon (KMP). METHOD: A retrospective analysis was conducted on the clinical data and follow-up data of 13 patients diagnosed with TA complicated by KMP. Five male and 8 female patients with an average age of 5.7 months (range, 29 days to 1 year) were treated with surgery between January 2009 and June 2012. According to the size and location of lesions and the degree of thrombocytopenia, complete or subtotal resection was performed. The median follow-up period was 3.4 years (range, 1.7 years to 5.2 years). Therapeutic outcomes were evaluated by platelet count and lesion size. RESULTS: Curative treatment of KMP is defined as restoration of normal hemostasis and elimination of tumor cells. Twelve patients achieved curative treatment and one died of multiple organ failure after operation. Ten patients received complete resection and three patients received incomplete resection. Thrombocyte count, hemoglobin and blood coagulation were respectively restored to normal levels within 1-3 days and 1-2 weeks post complete resection operation. One of the three patients who received subtotal resection operation died. In the other two patients, the platelet count fluctuated over time but remained above 60 × 109 /L, a significantly higher level than the preoperational level. Residual lesions slowly disappeared after continuous medication 3-6 months post operation. CONCLUSION: Early surgical treatment of patients with TA complicated with KMP resulted in significantly higher curative rate and reduced side-effects of drugs.

Inhibitory effects of isocryptotanshinone on gastric cancer.

Gastric cancer (GC) is one of the most common digestive malignancies globally, and the prognosis of patients with advanced tumors remains poor. Isocryptotanshinone (ICTS), isolated from Salvia miltiorrhiza, was found to inhibit the proliferation of lung and breast cancer cells. However, whether ICTS has anticancer activities against GC is unknown. In the present study, we reported that the proliferation of GC cells was inhibited by ICTS in a dose- and time-dependent manner. After treatment with ICTS, GC cells were arrested in the G1/G0 phase of cell cycle and the apoptotic cells were induced in a dose-dependent manner. Additionally, ICTS suppressed the expression of cell cycle- and apoptosis-associated proteins (e.g., Cyclin D1, phosphorylated Rb, E2F1, Mcl-1, Bcl-2, and Survivin). ICTS inhibited the phosphorylation of STAT3 in a dose-dependent manner. Down-regulated STAT3 attenuated the expression of Cyclin D1, p-Rb, and Survivin, which remarkably increased the sensitivity of ICTS in GC cells; overexpression of STAT3 restored the cell growth and proliferation and the protein expression suppressed by ICTS. ICTS also suppressed the xenograft tumor growth in BALB/c nude mice. Together, these data indicate that ICTS inhibits GC proliferation by inducing G1/G0 cell cycle arrest and apoptosis via inhibiting the STAT3 signaling pathway.

[The protective effect of tea polyphenols on chronic alcoholic liver injury in rats].

OBJECTIVE: To investigate the protective effects and potential mechanisms of tea polyphenols intervention on excess alcohol intake induced liver injury in rats. This study established the animal model of chronic liver injury rats induced by alcohol. Our results will provide experimental evidence for the effects of tea polyphenol on chronic alcoholic liver injury. METHODS: Alcohol-induced liver injury rat models were established, and the tea polyphenols intervention was performed in the meantime. After 8 weeks, rats were anesthetized, and visceral fat and liver samples were separated, weighted and stored. Visceral fat content was evaluated in fat/body weight ratio. Liver lipid accumulation was assessed by liver index and the result of Oil Red O staining. Hepatic superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity assay (T-AOC) and glutathione peroxidase (GSH-Px) activity were detected. And fatty acid translocase (FAT/CD36) protein level in liver was detected. RESULTS: Compared with the control group rats, the fat/body weight ratio, SOD/MDA, T-AOC and GSH-Px activity of chronic liver injury rats were decreased significantly (P<0.05,P<0.01). Meanwhile the liver index, FAT/CD36 protein level and lipid deposition in liver of chronic liver injury rats were increased (P<0.01). Compared with chronic liver injury rats, the tea polyphenols intervention increased fat/body weight ratio (P<0.05), and significantly increased SOD/MDA, T-AOC and GSH-Px activity (P<0.01). Meanwhile the tea polyphenols intervention reduced liver index (P<0.01), FAT/CD36 protein level (P<0.01) and lipid deposition in liver. CONCLUSIONS: Tea polyphenols intervention can improve lipid deposition and oxidative stress in chronic alcoholic liver, which is concurrent with decreased FAT/CD36 protein expression on the hepatocyte membrane.

Isofraxidin inhibited proliferation and induced apoptosis via blockage of Akt pathway in human colorectal cancer cells.

BACKGROUND: Isofraxidin (IF), a natural coumarin compound, has been reported to possess anti-cancer activity in human liver cancer. However, whether IF is involved in the regulation of colorectal cancer tumorigenesis and development has been not well elucidated. METHODS: The cell proliferation were assessed by Cell Counting Kit-8 (CCK-8) and colony formation test, respectively. The transwell assays were conducted to estimate cell migration and invasion abilities. Further, cell apoptosis was evaluated by confocal microscopy analysis, flow cytometry detection and TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of related protein. RESULTS: Herein, the result indicated that IF remarkably bated cell proliferation in human colorectal cancer cells HT-29 and SW-480 in a dose- and time-dependent manner. In addition, IF treatment showed obvious inhibitory activity to cell colony formation in HT-29 and SW-480 cells. Confocal microscopy analysis and flow cytometry detection revealed that IF dramatically induced cell apoptosis in HT-29 and SW-480 cells compared with the control. And IF markedly decreased the expression of anti-apoptotic protein bcl-2, whereas the expression of pro-apoptotic proteins, including caspase-3, caspase-9 and bax, notably increased in HT-29 and SW-480 cells. Besides, IF blocked Akt pathway via inhibition expression of p-Akt. Furthermore, MK2206, an Akt inhibitor, could inhibit cell colony formation and induced apoptosis. This effect is even more obvious in the presence of MK2206 and IF compared to that of either agent alone. CONCLUSIONS: Together, the present study reports a novel use of IF in mitigating human colorectal cancer proliferation and inducing apoptosis via blockage of Akt pathway.

Development of a novel hollow-fiber liquid-phase microextraction based on oil-in-salt and its comparison with conventional one.

A novel hollow-fiber liquid-phase microextraction based on oil-in-salt was proposed and introduced for the simultaneous extraction and enrichment of the main active compounds of hesperidin, honokiol, shikonin, magnolol, emodin, and ß,ß'-dimethylacrylshikonin in a formula of Zi-Cao-Cheng-Qi decoction and the single herb, Fructus Aurantii Immaturus, Cortex Magnoliae Officinalis, Radix et Rhizoma, and Lithospermum erythrorhizon, composing the formula prior to their analysis by high-performance liquid chromatography. The results obtained by the proposed procedure were compared with those obtained by conventional hollow-fiber liquid-phase microextraction, and the proposed procedure mechanism was described. In the procedure, a hollow-fiber segment was first immersed in organic solvent to fill the solvent in the fiber lumen and wall pore, and then the fiber was again immersed into sodium chloride solution to cover a thin salt membrane on the fiber wall pore filling organic solvent. Under the optimum conditions, the enrichment factors of the analytes were 0.6-109.4, linearities were 0.002-12 µg/mL with r2  ≥ 0.9950, detection limits were 0.6-12 ng/mL, respectively. The results showed that oil-in-salt hollow-fiber liquid-phase microextraction is a simple and effective sample pretreatment procedure and suitable for the simultaneous extraction and concentration of trace-level active compounds in traditional Chinese medicine.

Morphological factors and cardiac doses in whole breast radiation for left-sided breast cancer.

BACKGROUND: To investigate the impact of the breast size, shape, maximum heart depth (MDH), and chest wall hypotenuse (the distance connecting middle point of the sternum and the length of lung draw on the selected transverse CT slice) on the volumetric dose to heart with whole breast irradiation (WBI) of left-sided breast cancer patients. MATERIALS AND METHODS: Fifty-three patients with left-sided breast cancer undergoing adjuvant intensity-modulated radiotherapy (IMRT) were enrolled in the study. The primary breast size and shape, MHD and DCWH (chest wall hypotenuse) were contoured on radiotherapy (RT) planning CT slices. The dose data of hearts were obtained from the dose-volume histograms (DVHs). Data were analyzed by one-way analysis of variance (ANOVA), Student's t-test and linear regression analysis. RESULTS: Breast size was independent of heart dose, whereas breast shape, MHD and DCWH were correlated with heart dose. The shapes of breasts were divided into four types, as the flap type, hemisphere type, cone type and pendulous type with heart mean dose being 491.8±234.6 cGy, 752.7±219.0 cGy, 620.2±275.7 cGy, and 666.1±238.0 cGy, respectively. The flap type of breasts shows a strong statistically reduction in heart dose, compared to others (p=0.008 for V30 of heart). DCWH and MHD were found to be the most important parameters correlating with heart dose in WBI. CONCLUSIONS: More attention should be paid to the heart dose of non-flap type patients. The MHD was found to be the most important parameter to correlate with heart dose in tangential WBI, closely followed by the DCWH, which could help radiation oncologists and physicsts evaluate heart dose and design RT plan in advance.

Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair.

Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In the present study, we investigated the antidepressant- like potential of OEA in mice in comparison with clomipramine (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20 mL/kg, p.o.), OEA (2.5, 5-10mg/kg, p.o.), or Cp (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels. Likewise, in the drug-induced model of depression, OEA was given once daily at 10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4 mg/kg, i.p.) and the rectal temperature was measured at different time points. Consequently, head twitch behavior induced by intraperitoneal injection of 5-hydroxy-tryptophan (5-HTP; 300 mg/kg) were determined. The experimental data showed that OEA (2.5-10mg/kg) treatment significantly decreased the immobility as compared to the control group, and OEA (10mg/kg) treatment significantly increased 5-HTP-induced head twitch behavior and reversed reserpine-induced hypothermia and increased cerebral levels of NE and 5-HT. Thus, the antidepressant effects of OEA may be related to regulating central monoamine neurotransmitters.