Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Ablation of Shank1 Protects against 6-OHDA-induced Cytotoxicity via PRDX3-mediated Inhibition of ER Stress in SN4741 Cells.

BACKGROUND: Postsynaptic density (PSD) is an electron-dense structure that contains various scaffolding and signaling proteins. Shank1 is a master regulator of the synaptic scaffold located at glutamatergic synapses, and has been proposed to be involved in multiple neurological disorders. METHODS: In this study, we investigated the role of shank1 in an in vitro Parkinson's disease (PD) model mimicked by 6-OHDA treatment in neuronal SN4741 cells. The expression of related molecules was detected by western blot and immunostaining. RESULTS: We found that 6-OHDA significantly increased the mRNA and protein levels of shank1 in SN4741 cells, but the subcellular distribution was not altered. Knockdown of shank1 via small interfering RNA (siRNA) protected against 6-OHDA treatment, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. The results of RT-PCR and western blot showed that knockdown of shank1 markedly inhibited the activation of endoplasmic reticulum (ER) stress associated factors after 6-OHDA exposure. In addition, the downregulation of shank1 obviously increased the expression of PRDX3, which was accompanied by the preservation of mitochondrial function. Mechanically, downregulation of PRDX3 via siRNA partially prevented the shank1 knockdowninduced protection against 6-OHDA in SN4741 cells. CONCLUSION: In summary, the present study has provided the first evidence that the knockdown of shank1 protects against 6-OHDA-induced ER stress and mitochondrial dysfunction through activating the PRDX3 pathway.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study.

OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL). METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded. RESULTS: The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group. CONCLUSIONS: TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.

BACKGROUND: Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation. METHODS: We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice. RESULTS: Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC). CONCLUSIONS: Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.

Application of Multigroup Technology in Non-Small-Cell Lung Cancer with Qi Stagnation and Blood Stasis Syndrome.

OBJECTIVE: To explore the basic characteristics of intestinal flora, metabolomics, and proteomics of non-small cell lung cancer (NSCLC) in patients with Qi stagnation and blood stasis syndrome. METHODS: Twelve NSCLC patients with Qi stagnation and blood stasis syndrome were selected for the QZXY group and 15 healthy volunteers were selected for the control group. Fecal samples from the two groups were collected to evaluate intestinal microecology using the 16s rDNA technique. Serum samples were collected to compare the differences in metabolomics and proteomics between the two groups using liquid chromatography-mass spectrometry (LC-MS). Another 34 NSCLC patients with other syndromes were selected for the nQZXY group and their serum samples were collected. Metabolomics differences between the QZXY and nQZXY groups were compared using LC-MS, and four metabolites with the most obvious differences were selected for receiver operation characteristic curve representation. Finally, multigroup results were analyzed using the WGCNA software. RESULTS: There were two significantly different types of bacteria (Aerococcaceae and Abiotrophia), 11 different proteins (six upregulated and five downregulated), and 38 different metabolites (nine upregulated, 29 downregulated) between the QZXY and control groups. There was a correlation between differential bacteria, proteins, and metabolites. The conjoint analysis found that the different substances were related to MAPK, PI3K/Akt, Ras signaling pathway, cancer pathways, and cytokine-cytokine receptor interaction. There were four significant differences in metabolites (Pseudouridine, phenlacetyl-C0A, L-glutamic, and phospho-anandamide) between the QZXY and nQZXY groups. CONCLUSIONS: NSCLC with Qi stagnation and blood stasis syndrome had specific intestinal flora and protein and metabolites, which were closely related to the occurrence and development of tumors.

Asymmetric synthesis of chiral organosilicon compounds via transition metal-catalyzed stereoselective C-H activation and silylation.

This feature article details the progress of transition metal-catalyzed stereoselective sp2 and sp3 C-H activation and silylation in the synthesis of chiral organosilicon compounds, and the asymmetric C-H silylation includes intramolecular cyclizing silylation and intermolecular silylation. The silylating reagents include monohydrosilanes, dihydrosilanes, silacylcobutanes and disilanes. In general, catalytic systems include a transition metal salt as the catalyst and a chiral ligand. No external chiral ligand is required in some cases where the chiral substrates act as the source of chirality. Many kinds of silylated compounds with central, axial, planar, or helical chirality have been constructed via C-H activation by asymmetric rhodium, iridium or palladium catalysis. Some pharmacophores and material building blocks were successfully introduced into the target molecules. Some silylated products proved to be useful in medicinal chemistry, synthetic organic chemistry, and materials science. Besides reaction development, mechanisms for stereoselective C-H activation and silylation are also discussed.

Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network.

The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

Transition metal-catalyzed sp3 C-H activation and intramolecular C-N coupling to construct nitrogen heterocyclic scaffolds.

Nitrogen heterocycles are of great medicinal importance, and the construction of nitrogen heterocyclic scaffolds has been one of the focuses in synthetic organic chemistry. Recently, the strategy of transition metal-catalyzed sp3 C-H activation and intramolecular C-N coupling to construct nitrogen heterocyclic scaffolds has been well developed. Palladium, copper, silver, nickel, cobalt, ruthenium and rhodium catalysis were successfully used for the construction of nitrogen heterocyclic scaffolds, aziridines, azetidines, pyrrolidines, pyrrolidine-2,5-diones, indolines, isoindolines, isoindolinones, tetrahydropyridines, oxazolidinones, oxazinanones, ß-lactams, γ-lactams etc., which have been synthesized by the sp3 C-H activation strategy. Here, we summarize the progress of transition metal-catalyzed sp3 C-H activation/intramolecular C-N bond formation, and introduce both the reaction development and mechanisms in numerous synthetically useful intramolecular sp3 C-H catalytic aminations/amidations.

Babaodan Capsule () combined with Qingyi Huaji Formula () in advanced pancreatic cancer-a feasibility study.

OBJECTIVE: To observe the clinical effects of Babaodan Capsule (, BBD) combined with Qingyi Huaji Formula (, QYHJ) in treating patients with advanced pancreatic cancer. METHODS: Eighty-one patients with advanced pancreatic cancer (from January 1, 2013 to December 31, 2014) were enrolled. Patients were assigned to two groups: QYHJ plus BBD group (40 cases) and QYHJ only group (41 cases), and there were no significant differences for other treatment between two groups. The survival and cancer-related symptoms were compared between two groups over two cycles of treatment. RESULTS: The cancer-related symptoms of patients such as ascites, jaundice, pain, abdominal distension, anorexia and Karnofsky performance status of QYHJ plus BBD group were significantly improved as compared with those of the QYHJ group (P<0.01). In addition, the 1-year survival rate of patients in QYHJ plus BBD group was longer than that in the QYHJ group (65% vs. 33%, respectively, P=0.0023). CONCLUSIONS: BBD with QYHJ is feasible treatment to prolong the survival of patients with advanced pancreatic cancer. However, it deserves to be further investigated in randomized clinical trials.

Excess copper induced proteomic changes in the marine brown algae Sargassum fusiforme.

Copper (Cu) is an essential micronutrient for algal growth and development; however, it is also generally considered to be one of the most toxic metals when present at higher levels. Seaweeds are often exposed to low concentrations of metals, including Cu, for long time periods. In cases of ocean outfall, they may even be abruptly exposed to high levels of metals. The physiological processes that are active under Cu stress are largely unknown. In this study, the brown macroalga Sargassum fusiforme was cultured in fresh seawater at final Cu concentrations of 0, 4, 8, 24 and 47 µM. The Cu(2+) concentration and chlorophyll autofluorescence were measured to establish the toxic effects of Cu on this economically important seaweed. The accumulation of Cu by S. fusiforme was also dependent upon the external Cu concentration. Algal growth displayed a general decline with increasing media Cu concentrations, indicating that S. fusiforme was able to tolerate Cu stress at low concentrations, while it was negatively impacted at high concentrations. The term "acute stress" was employed to indicate exposure to high Cu concentrations for 1 day in this study. On the other hand, "chronic stress" was defined as exposure to lower sub-lethal Cu concentrations for 7 days. Proteins were extracted from control and Cu-treated S. fusiforme samples and separated by two-dimensional gel electrophoresis. Distinct patterns of protein expression in the acute and chronic stress conditions were observed. Proteins related to energy metabolism and photosynthesis were reduced significantly, whereas those related to carbohydrate metabolism, protein destination, RNA degradation and signaling regulation were induced in S. fusiforme in response to acute copper stress. Energy metabolism-related proteins were significantly induced by chronic Cu stress. Proteins from other functional groups, such as those related to membranes and transport, were present in minor quantities. These results suggest that S. fusiforme is sensitive to excess Cu, regardless of the presence of acute or chronic stress. We discuss the possible function of these identified proteins, taking into consideration the information available from other plant models.

Folate intake, serum folate levels, and prostate cancer risk: a meta-analysis of prospective studies.

BACKGROUND: Studies have reported inconsistent results concerning the existence of associations of folate intake and serum folate levels with prostate cancer risk. This study sought to summarise the evidence regarding these relationships using a dose-response meta-analysis approach. METHODS: In January 2014, we performed electronic searches of PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate on the incidence of prostate cancer. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of the incidence of prostate cancer for more than 2 categories of folate were included. RESULTS: Overall, we included 10 prospective studies reporting data on 202,517 individuals. High dietary folate intake had little or no effect on prostate cancer risk (risk ratio [RR] = 1.02; 95% CI = 0.95-1.09; P = 0.598). The dose-response meta-analysis suggested that a 100 µg per day increase in dietary folate intake has no significant effect on the risk of prostate cancer (RR = 1.01; 95% CI = 0.99-1.02; P = 0.433). However, high serum folate levels were associated with an increased risk of prostate cancer (RR = 1.21; 95% CI = 1.05-1.39; P = 0.008). The dose-response meta-analysis indicated that a 5 nmol/L increment of serum folate levels was also associated with an increased risk of prostate cancer (RR = 1.04; 95% CI = 1.00-1.07; P = 0.042). CONCLUSIONS: Our study indicated that dietary folate intake had little or no effect on prostate cancer risk. However, increased serum folate levels have potentially harmful effects on the risk of prostate cancer.

Maintenance of self-incompatibility in peripheral populations of a circumboreal woodland subshrub.

Compared with self-incompatible (SI) species, species that shift to self-compatibility (SC) are more likely to colonize a new habitat. Self-incompatibility and fruit-set failure have been widely reported in European populations of Linnaea borealis (twinflower), whereas at the eastern margin of its North American distribution it showed potential SC. We investigated the breeding system of L. borealis in northwestern China, the eastern margin of the species' distribution in Eurasia. Pollinators, breeding system and pollen limitation were examined in a nature reserve with thousands of L. borealis individuals. To investigate whether fruit set was limited by mating opportunity, we compared fruit set in high-, medium- and low-density patches of L. borealis. To examine whether clonal reproduction resulted in higher fruit-set failure, we compared fruit set among different sizes of clonal ramets. Flies contributed most pollinator visits in the studied population. It was strictly SI and natural fruit set depended on insect visits. Patch density comparisons showed that L. borealis was not pollen limited in low-density patches that had significantly fewer flowers. However, it produced significantly fewer fruits per flower when clonal ramet size increased, suggesting that the high failure of fruit set in larger clones with more flowers may be caused by geitonogamy. Generalist pollinators and clonal reproduction may help L. borealis to colonize in marginal areas without the transition of the breeding system from SI to SC, but experiencing fruit-set failure resulting from geitonogamy within clones.

[PTK7 mRNA and protein expression level in serum of patients with acute lymphocytic leukemia and its clinical significance].

The purpose of this study was to detect the serum PTK7 level of patients with acute lymphocytic leukemia, and to reveal its clinical value for diagnosis of diseases. A total of 136 patients diagnosed as acute lymphocytic leukemia from May 2012 to April 2014 in our hospital were enroled in this study and were divided into the L1 group (n = 42), L2 (n = 45) and L3 group (n = 49) according cytomorphology, and 48 normal children were selected as control group. Fluorescence quantitative PCR was used to detect mRNA level of PTK7 in peripheral blood mononuclear cells, and Western blot was used to detect PTK7 protein expression. The results showed that the PTK7 mRNA level in L1 group was significantly higher than that in normal group (P = 0.000) . The PTK7 mRNA level in L2 group was significantly higher than that in the L1 group (P = 0.000). The PTK7 mRNA level in L3 group and L2 group had not significantly different between each other (P = 0.123). Serum PTK7 protein level in L1 group was very significantly higher than that in normal group (P = 0.000) . The serum PTK7 protein level in L2 group were very significantly higher than that in the L1 group (P = 0.003) and serum PTK7 protein level in L3 and L2 group had no significance difference (P = 0.312) . It is concluded that the expression level of serum PTK7 protein has a potential clinical value for the diagnosis of acute lymphocytic leukemia, but without specificity for ALL subsets.

Behavior of the edible seaweed Sargassum fusiforme to copper pollution: short-term acclimation and long-term adaptation.

Aquatic agriculture in heavy-metal-polluted coastal areas faces major problems due to heavy metal transfer into aquatic organisms, leading to various unexpected changes in nutrition and primary and/or secondary metabolism. In the present study, the dual role of heavy metal copper (Cu) played in the metabolism of photosynthetic organism, the edible seaweed Sargassum fusiforme, was evaluated by characterization of biochemical and metabolic responses using both 1H NMR and GC-MS techniques under acute (47 µM, 1 day) and chronic stress (8 µM, 7 days). Consequently, photosynthesis may be seriously inhibited by acute Cu exposure, resulting in decreasing levels of carbohydrates, e.g., mannitol, the main products of photosynthesis. Ascorbate may play important roles in the antioxidant system, whose content was much more seriously decreased under acute than that under chronic Cu stress. Overall, these results showed differential toxicological responses on metabolite profiles of S. fusiforme subjected to acute and chronic Cu exposures that allowed assessment of impact of Cu on marine organisms.

Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell MDA-MB-231 In Vitro.

Objective. To evaluate the effect of petroleum ether extracts of Curcuma zedoaria on the proliferation of human triple negative breast cancer cell line MDA-MB-231. Methods. The reagents were isolated from Curcuma zedoaria by petroleum ether fraction. It was assayed by CCK8 for MDA-MB-231 cellular viability with various concentrations and days, cell cycle analyses, Western Blot analysis, and Realtime Reverse Transcriptase PCR analyses for chemokines molecules including E-cadherin, and E-selectin, and adhesion molecules including CCR7, SLC, SDF-1, and CXCR4. Epirubicin was used as control in the study. Results. MDA-MB-231 cells were inhibited by petroleum ether extracts of Curcuma zedoaria (P < 0.05), and the inhibition rate was dependent on concentrations and time. Petroleum ether extracts of Curcuma zedoaria as well as Epirubicin produce a significant G0/G1 cell cycle arrest. The level of expression of proteins E-cadherin and E-cadherin mRNA was significantly increased, while proteins SDF-1, CCR7, and CXCR4 mRNA were decreased after being incubated with petroleum ether extracts of Curcuma zedoaria at the concentrations of 300 µ g/mL than control (P < 0.05). The differences were that the protein CXCR4 mRNA expression level was higher than vehicle. Conclusions. MDA-MB-231 cells were inhibited by petroleum ether extracts of Curcuma zedoaria.

Lack of associations of polymorphisms of IL-7R, IL-13 and IL-15 with NSCLCs in non-smoking Chinese.

Studies have shown that immune cells play a key role in lung cancer development. Five SNPs (rs1494555, rs7737000, rs20541, rs1057972 and rs2857261) are associated with lung cancer risk among Caucasians and/or African-Americans, but the polymorphisms may be implicated in different susceptibilities for lung cancer across different populations because of underlying genetic heterogeneity. We therefore conducted a study to examine this relationship in non-smoking Chinese. As a result , no significant associations were observed between SNPs and NSCLCs, whetehr of squamous cell or adenocarcinoma type. Results indicated polymorphisms of IL-7R, IL-13 and IL-15 are not major contributors to NSCLC susceptibility, although we can not rule out synergistic effects with cigarette smoke in NSCLC development in smoking Chinese.

[Tissue culture and rapid propogation of seeds of Uyghur traditional herbal Capparis spinosa].

OBJECTIVE: To optimize the tissue culture and rapid proliferation techniques of seeds of Capparis spinosa for producing large scale seedlings. METHODS: The seeds of Capparis spinosa were collected as explants and cultivated in different MS media, which were from Turpan in Xinjiang. The optimum media were selected by adjusting the combinations of different hormone and concentration. RESULTS: The best on institution of asepsis explants was rinsing for 8 hours and 0.1% HgCl2 for 12 minutes. The medium MS + 6-BA 0.6 mg/L + NAA 0.1 mg/L was suitable for primary and second culture. The medium MS + 6-BA 0.6 mg/L + 2,4-D 1.0 mg/L was suitable for proliferation, and the optimum medium of rooting was MS + IBA 0.8 mg / L + 300 mg/L activated carbon. CONCLUSION: The rapid proliferation technique of seeds of Capparis spinosa can be used for producing large scale seedlings.

Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity.

The systemic plasma pharmacokinetics of genistein were determined in rats to evaluate the absolute oral bioavailability and make comparison with similar data in the literature derived from humans subjects. The plasma concentrations of genistein, genistein glucuronide and carbon-14 were determined by LC-MS/MS and liquid scintillation counting following oral and intravenous dosing with [14C]genistein (4 mg kg(-1) body weight). The absorption of total radioactivity from the gut, (parent compound and metabolites), was 56 and 111% in male and female rats, respectively. In contrast, the absolute oral bioavailability of genistein in male and female rats was 7 and 15%. There was a significant (P<0.001) difference between Cmax of genistein after intravenous (6921 and 4392 ng/ml) and oral (21 and 22 ng/ml) dosing in male and female rats, respectively. After oral administration, the concentration profile of genistein glucuronide in plasma greatly exceeded that of parent compound during the absorption/distribution phase suggesting extensive first pass metabolism, and provided evidence of entero-hepatic circulation. Selective plasma analysis by LC-MS/MS, without prior enzymatic hydrolysis, enabled ready discrimination between parent and conjugated metabolites and prevented gross overestimation of genistein bioavailability. Pharmacokinetic parameters Cmax, Tmax and AUC were similar to those reported in humans, which supports the use of the rat model for genistein toxicity studies.