Improving Antioxidative and Antiproliferative Properties Through the Release of Bioactive Compounds From Eucommia ulmoides Oliver Bark by Steam Explosion.

Eucommia ulmoides Oliver bark is a potential medicinal plant-based feedstock for bioactive products and possesses the effective functions of antioxidant and antitumor. Network pharmacology was employed to reveal the oxidative and free radical damage and cancer-related potential compounds of Eucommia ulmoides Oliver in this study. The result showed that quercetin might be the key compound to resist these two types of diseases. Then, the effect of steam explosion on the release of bioactive compounds and the antioxidative and antiproliferative properties of the extract from Eucommia ulmoides Oliver bark were investigated. Results showed that steam explosion at 0.7 MPa for 30 min significantly enhanced the total phenolic, total flavonoids, and quercetin content of Eucommia ulmoides Oliver bark. Reducing power and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity of the steam-exploded extracting solution were 1.72 and 2.76 times of native. The antiproliferative activity to CT26 and HepG2 of the extract from steam-exploded Eucommia ulmoides Oliver bark (SEU) was higher than those of native-exploded Eucommia ulmoides Oliver bark (NEU). All these results suggested that steam explosion could be applied to release the bioactive compounds, thus enhanced the antioxidative and antiproliferative activities of medicinal and edible plant-based sources.

Anti-breast-cancer activity of self-fermented Bovistella sinensis Lloyd extracts through the mitochondrial ROS-induced apoptosis in vitro.

Bovistella sinensis (BS) Lloyd was medically used by Chinese folks and associated with various bioactivities. In this study, dry fruiting body of Bovistella sinensis (BS) Lloyd was self-fermented to improve the anti-breast-cancer activity and the mitochondrial ROS-induced apoptosis of key compound was investigated. BS extracts obtained with petroleum ether, ethyl acetate, n-butanol, ethanol, and distilled water showed various inhibitory effects on the proliferation of MDA-MB-231. The various self-fermented BS extracts had a better effect on inhibition of MDA-MB-231 proliferation than that of untreated. And the ethyl acetate extract was found having the highest inhibitory effect on MDA-MB-231 proliferation, which was further separated into seven fractions. And among these fractions, fraction 6 exhibited the highest performance, where the major component F was obtained. The inhibition rate of 50 µg/ml of component F on MDA-MB-231, MCF-7, and MCF-10A were 60.12%, 56.16%, and 6.45%, respectively, showed the low toxicity in normal cell line. When treated with F, the activity and the mitochondrial membrane potential of MDA-MB-231 cells decreased significantly, while the intracellular reactive oxygen species increased, showed that the mitochondrial pathway was induced by reactive oxygen species. The HPLC, 1 H NMR, 13 C NMR, and 2D NMR analysis showed component F may be a kind of fatty acid or ester. Therefore, self-fermentation may be an efficient technology that could improve anti-tumor activity and component F from self-fermented BS might be considered as an anti-cancer ingredient applied in functional food and anti-carcinogen. PRACTICAL APPLICATIONS: Anti-breast-cancer activity and mechanism of self-fermented Bovistella sinensis Lloyd extract were investigated. The ethyl acetate extract showed a comparatively higher inhibitory effect and was separated into seven fractions. Fraction 6 showed the strongest cytotoxic activity against MDA-MB-231 breast cancer cell line and obtained a major component F with low cytotoxicity in a normal cell line. Component F had the potential to be used as natural anti-cancer agents.

The Adjunctive Effect of Acupuncture for Advanced Cancer Patients in a Collaborative Model of Palliative Care: Study Protocol for a 3-Arm Randomized Trial.

BACKGROUND: Cancer is the second leading cause of death before the age of 70. Improved cancer survival has put increasing demands on cancer care. Palliative care is the specialized multi-disciplinary care providing relief from the pain, symptoms, and stress of serious illness. The study aims to evaluate the adjunctive effect of acupuncture for advanced cancer patients in a collaborative model of palliative care. METHODS/DESIGN: This is a single-blinded, randomized, sham-controlled trial. One hundred twenty advanced cancer patients undergoing palliative care will be randomized in a ratio of 2:1:1 to manual acupuncture plus standard care group (ASC), sham acupuncture plus standard care group (SSC), and standard care group (SC). Patients in ASC and SSC will receive 9 sessions of acupuncture or sham acupuncture for 3 weeks, and will be followed up for 2 months. The primary measure is the change from baseline score of the Edmonton Symptom Assessment System at 3 weeks. The secondary measures include the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Numeric Rating Scale, and European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care. DISCUSSION: The finding of this trial will provide high-quality evidence on the adjunctive effect of acupuncture to standard care on advanced cancer patients undergoing palliative care. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04398875 (https://www.clinicaltrials.gov/ct2/show/NCT04398875), Registered on 21 May 2020.

Suppression of the NF­κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)­κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo­preventative effects against the intestinal malignancy formation. In the present study, cell counting kit­8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription­polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT­29 cells. In addition, the cDNA expression of cyclooxygenase­2, and the protein expression and activity of NF­κB and tumor necrosis factor­α were downregulated; however, the protein expression of cleaved caspase­3 and ­9, and cleaved poly (adenosine diphosphate­ribose) polymerase, and the B­cell lymphoma (Bcl)­2: Bcl­2­associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF­κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT­29 cells, which may be associated with the blocking of the NF­κB signaling pathway. Thus, Riccardin D should be investigated as an NF­κB inhibitor in cancer therapy.

Blood-based biomarkers for precision medicine in lung cancer: precision radiation therapy.

Both tumors and patients are complex and models that determine survival and toxicity of radiotherapy or any other treatment ideally must take into account this variability as well as its dynamic state. The genetic features of the tumor and the host, and increasingly also the epi-genetic and proteomic characteristics, are being unraveled. Multiple techniques, including histological examination, blood sampling, measurement of circulating tumor cells (CTCs), and functional and molecular imaging, can be used for this purpose. However, the effects of radiation on the tumor and on organs at risk (OARs) are also influenced by the applied dose and volume of irradiated tissues. Combining all these biological, clinical, imaging, and dosimetric parameters in a validated prognostic or predictive model poses a major challenge. Here we aimed to provide an objective review of the potential of blood markers to guide high precision radiation therapy. A combined biological-mathematical approach opens new doors beyond prognostication of patients, as it allows truly precise oncological treatment. Indeed, the core for individualized and precision medicine is not only selection of patients, but even more the optimization of the therapeutic window on an individual basis. A holistic model will allow for determination of an individual dose-response relationship for each organ at risk for each tumor in each individual patient for the complete oncological treatment package. This includes, but is not limited to, radiotherapy alone. Individualized dose-response curves will allow for consideration of different doses of radiation and combinations with other drugs to plan for both optimal toxicity and complete response. Insights into the interactions between a multitude of parameters will lead to the discovery of new pathways and networks that will fuel new biological research on target discovery.

Platelet releasate promotes breast cancer growth and angiogenesis via VEGF-integrin cooperative signalling.

BACKGROUND: Selective platelet release of pro- or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth. METHODS: Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors). RESULTS: The PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary-like tube formation of endothelial cells that was further enhanced by pro-angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1α, receptor blockade abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB-231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4-PR, and seemed to achieve the exaggeration by promoting more profound tumour angiogenesis. CONCLUSIONS: Platelet releasate increases breast cancer cell proliferation through VEGF-integrin cooperative signalling. Pro-angiogenic factor-rich platelet releasate enhances cancer cell-induced angiogenesis more markedly, and thus exaggerates tumour growth in vivo.

Survival impact of postoperative therapy modalities according to margin status in non-small cell lung cancer patients in the United States.

OBJECTIVE: Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non-small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them. METHODS: Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology. RESULTS: We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P < .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone. CONCLUSIONS: NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection.

Tetramethypyrazine inhibits renal cell carcinoma cells through inhibition of NKG2D signaling pathways.

Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer efficacy of TMP was investigated in human clear cell renal cell carcinoma (ccRCC) cells. We showed that TMP significantly inhibited ccRCC cell viability, proliferation, apoptosis, invasion and migration through the methods of MTT, flow cytometry, wound healing and transwell assays. Furthermore, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunofluorescence results demonstrated TMP upregulation of the expression of NKG2D ligands (NKG2DLs) MHC class I chain-related molecules A and B (MICA/B) and epithelial cell expression marker of E-cadherin, and downregulation of mesenchymal cell expression markers of vimentin and fibronectin. Taken together, the inhibition of TMP on ccRCC cells might be mediated via inhibition of NKG2D related signaling pathway to further suppress epithelial-mesenchymal transition (EMT) progression. The binding of NKG2D to its ligands activates NK cells, giving the rationale for studies on the utilization of TMP as a potential cancer therapeutic compound to increase NK cells-mediated cytotoxicity against high MICA/B expression in cancer cells.

Brain regions involved in dispositional mindfulness during resting state and their relation with well-being.

Mindfulness can be viewed as an important dispositional characteristic that reflects the tendency to be mindful in daily life, which is beneficial for improving individuals' both hedonic and eudaimonic well-being. However, no study to date has examined the brain regions involved in individual differences in dispositional mindfulness during the resting state and its relation with hedonic and eudaimonic well-being. To investigate this issue, the present study employed resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional homogeneity (ReHo) that measures the local synchronization of spontaneous brain activity in a large sample. We found that dispositional mindfulness was positively associated with the ReHo in the left orbitofrontal cortex (OFC), left parahippocampal gyrus (PHG), and right insula implicated in emotion processing, body awareness, and self-referential processing, and negatively associated with the ReHo in right inferior frontal gyrus (IFG) implicated in response inhibition and attentional control. Furthermore, we found different neural associations with hedonic (i.e., positive and negative affect) and eudaimonic well-being (i.e., the meaningful and purposeful life). Specifically, the ReHo in the IFG predicted eudaimonic well-being whereas the OFC predicted positive affect, both of which were mediated by dispositional mindfulness. Taken together, our study provides the first evidence for linking individual differences in dispositional mindfulness to spontaneous brain activity and demonstrates that dispositional mindfulness engages multiple brain mechanisms that differentially influence hedonic and eudaimonic well-being.

Pretreatment with baicalin attenuates hypoxia and glucose deprivation-induced injury in SH-SY5Y cells.

OBJECTIVE: To explore the neuroprotective effects of baicalin against hypoxia and glucose deprivation-reperfusion (OGD/RO)-induced injury in SH-SY5Y cells. METHODS: SH-SY5Y cells were divided into a control group, a OGD/RO group, which was subject to OGD/RO induction; and 3 baicalin groups subject to baicalin (1, 5, 25 µmol/L) for 2 h before induction of OGD/RO (low-, medium-, and high-dose baicalin groups). Cell viability was detected by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometric analysis was used to detect cell apoptosis. Real-time polymerase chain reaction was performed to determine the mRNA expression of caspase-3 gene. Western blot analysis was conducted to determine the expression of nuclear factor (NF)-κB and N-methyl-daspartic acid receptor-1 (NMDAR1). RESULTS: Baicalin could significantly attenuate OGD/RO mediated apoptotic cell death in SH-SY5Y cells; the apoptosis rates in the low-, medium- and high-dose groups were 12.1%, 7.9%, and 5.4%, respectively. Western blot and real-time PCR analysis revealed that significant decrease in caspase-3 expression in the baicalin group compared with the OGD/RO group (P<0.01). Additionally, down-regulation of NF-κB and NMDAR1 was observed in the baicalin group compared with those obtained from the OGD/RO group. Compared with the low-dose baicalin group, remarkable decrease was noted in the medium- and high-dose groups (P<0.01). CONCLUSION: Baicalin pre-treatment attenuates brain ischemia reperfusion injury by suppressing cellular apoptosis.

Ursolic Acid Induces Apoptosis of Prostate Cancer Cells via the PI3K/Akt/mTOR Pathway.

Ursolic acid (UA), a pentacyclic triterpenoid, is known to exert antitumor activity in breast, lung, liver and colon cancers. Nonetheless, the underlying mechanism of ursolic acid in prostate cancer cells still remains unclear. In the present study, we report the chemotherapeutic effects of ursolic acid as assessed using in vitro and in vivo models. Treatment of human prostate cancer cells (LNCaP and PC-3) with UA inhibited the proliferation and induced apoptosis in both cell lines as characterized by the increased Annexin V-binding. The induction of apoptosis by UA was associated with a decrease in the levels of Bcl-2, Bcl-xl, survivin, and activated caspase-3. Treatment with UA also inhibited the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylation of Akt and mTOR signaling proteins. Further, administration of UA significantly inhibited the growth of LNCaP prostate tumor xenografts in athymic nude mice, which was associated with inhibition of cell proliferation, induction of apoptosis of tumor cells and decreased expression of PI3K downstream factors, such as p-Akt and p-mTOR in tumor xenograft tissues. Our study demonstrates that UA not only inhibits cell growth but also induces apoptosis through modulation of the PI3K/Akt/mTOR pathway in human prostate cancer cells. We suggest that UA may be a new chemotherapeutic candidate against prostate cancer.

Characteristics of oxidation-reduction potential, VFAs, SCOD, N, and P in an ATAD system under different thermophilic temperatures.

One-stage autoheated thermophilic aerobic digestion (ATAD) can stabilize sludge to meet class A standard. In this study, batch experiments were conducted to investigate the characteristics of oxidation-reduction potential (ORP), volatile fatty acids (VFAs), soluble chemical oxygen demand (SCOD), and nutrients at different temperatures (45, 55, and 65 °C) in the one-stage ATAD. Results showed that the ORP values remained between approximately -350 and -120 mV in the primary 5-day digestion despite of excessive aeration in the digester, indicating that the aeration level could be decreased in an ATAD system to save energy. The pH exhibited a poor correlation (R (2) < 0.11) with ORP, indicating that some variables synthetically effected on pH. Digestion at 65 °C caused more intercellular compounds released because of the highest concentrations of SCOD, VFA, nitrogen (N) and phosphorus (P) in the solution among three digestion temperatures. The volatile suspended solid (VSS) removal rate for sludge at 55 °C was the highest among three digestion temperatures, reaching 41.4 % on day 13 and meeting Class A standard. VSS removal rate of 30.1 % under 65 °C did not satisfy the effluent standard because of the high soluble content of ammonium nitrogen. The majority of nitrogen and phosphorus left in the sludge supernatant under 65 °C could hinder its further use for land applications. Therefore, the optimal temperature of 55 °C is suitable for the ATAD process.

Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways.

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7- AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

[Effects of electroacupuncture on embryo implanted potential for patients with infertility of different symptom complex].

OBJECTIVE: To explore the impacts of electroacupuncture on embryo implanted potential and its molecular mechanism in the patients with infertility of different symptom complex. METHODS: Among the patients with infertility treated with electroacupuncture and in vitro fertilization and embryo transplantation (IVF-ET), 82 cases of kidney deficiency (group A), 74 cases of liver qi stagnation (group B) and 54 cases of phlegm dampness (group C) were selected. All of the patients in three groups received long-program ovarian hyper-stimulation. Additionally, electroacupuncturecan was applied before controlled ovarian hyper-stimulation (COH) and in the process of ovarian hyper-stimulation. The levels of human leukocyte antigen-G (HLA-G) in the serum were determined on the 2nd day of the menstruation (M2), on the day of human Chorionic Gonadotropin (hCG) injection and on the day of embryo transplantation in the culture solution in three groups separately. The fertilization rate, implantation rate and clinical pregnancy rate were observed for the patients in three groups. RESULTS: The levels of HLA-G in the serum on hCG injection day and in the culture solution on embryo transplantation day in group A and B were significantly higher than those in group C (all P < 0.05). But, there was no significant difference in serum HLA-G levels on M2 day among three groups. The high-quality embryo rate in either group A (73.6%, 352/478) or group B (70.6%, 379/537) was higher significantly than that in group C (54.2%, 208/384) separately, presenting statistical significant difference (all P < 0.01). But there were no significant differences in clinical pregnancy rate, fertilization rate and cleavage rate among three groups. CONCLUSION: Electroacupuncture can increase the contents of HLA-G in the body and the level of HLA-G secreted in embryos for the patients in the process of IVF-ET. Eventually, the pregnancy outcome and the pregnancy rate are improved. The clinical effects of electroacupuncture for the patients of kidney deficiency and liver qi stagnation are better than those for the patients of phlegm dampness.

Components representation of negative numbers: evidence from auditory stimuli detection and number classification tasks.

Past research suggested that negative numbers could be represented in terms of their components in the visual modality. The present study examined the processing of negative numbers in the auditory modality and whether it is affected by context. Experiment 1 employed a stimuli detection task where only negative numbers were presented binaurally. Experiment 2 employed the same task, but both positive and negative numbers were mixed as cues. A reverse attentional spatial-numerical association of response codes (SNARC) effect for negative numbers was obtained in these two experiments. Experiment 3 employed a number classification task where only negative numbers were presented binaurally. Experiment 4 employed the same task, but both positive and negative numbers were mixed. A reverse SNARC effect for negative numbers was obtained in these two experiments. These findings suggest that negative numbers in the auditory modality are generated from the set of positive numbers, thus supporting a components representation.

Sesquiterpenoids from myrrh inhibit androgen receptor expression and function in human prostate cancer cells.

AIM: To examine whether two naturally occurring sesquiterpenoids (ST1 and ST2) with anti-proliferative activity in prostate cancer cells inhibit androgen receptor (AR) signaling. METHODS: Human prostate cancer cell lines LNCaP and PC3 were used. The expression of AR, AR translocation into the nucleus, and expression levels of AR coactivators ARA70 and steroid receptor coactivator-1 (SRC-1) in LNCaP cells were examined using real-time PCR and Western blot. Changes in prostate-specific antigen (PSA) protein levels, PSA promoter activity, and androgen response element (ARE)-mediated reporter gene activity were examined using enzyme-linked immunoabsorbent assay (ELISA) and transient transfection assays. Co-immunoprecipitation was performed to analyze the interaction between AR and the AR coactivators in ST1- and ST2-treated cells. RESULTS: In LNCaP cells, ST1 and ST2 (40 µmol/L) led to a significant decrease in the expression of AR as well as a reduction of AR translocation into the nucleus, but had no effect on AR protein translation. ST1 and ST2 treatment also resulted in a significant decrease in the level of PSA protein secreted into the medium and was able to suppress PSA promoter-dependent and ARE-dependent luciferase activity. Furthermore, decreased expression of ARA70 and SRC-1 was observed when LNCaP cells were exposed to ST1 and ST2, which interfered with their ability to interact with AR. CONCLUSION: The observations suggest that suppression of AR transactivation by ST1 and ST2 may be mediated, in part, by inhibiting AR nuclear translocation and/or interfering with the interaction between AR and its coactivators ARA70 and SRC-1. Therefore, sesquiterpenoids could be developed as novel therapeutic agents for treating prostate cancer.

Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin.

OBJECTIVES: It has been hypothesized that the accumulation of beta-amyloid peptide (Abeta) in the brain is a triggering event leading to the pathological cascade of Alzheimer's disease. The steady-state levels of Abeta are determined by the metabolic balance between anabolic and catabolic activity and the dysregulation of this activity leads to Alzheimer's disease. Recent evidence has shown that neprilysin (NEP) is the rate-limiting enzyme in the Abeta degradation in the brain. Ginseng, the root of Panax ginseng C.A. Meyer, is widely used as a tonic for the prevention and treatment of age-related disorders in China. We aimed to investigate the basis of this use. METHODS: In this study, we investigated the effect of ginsenoside Rg3, one of the major active components of ginseng, on the metabolism of Abeta40 and Abeta42 in SK-N-SH cells transfected with Swedish mutant beta-amyloid precursor protein (SweAPP). RESULTS: The ELISA result showed that Rg3 significantly reduced the levels of Abeta40 and Abeta42, 19.65 +/- 6.05%, 23.61 +/- 6.74%, respectively (P < 0.01). The Western blot analysis showed that Rg3 reduced the levels of Abeta40 and Abeta42 through enhancing NEP gene expression, and real-time PCR assay showed that 50 microM Rg3 could significantly enhance NEP gene expression (2.9 fold at 48 h). CONCLUSIONS: Our findings suggest that the Rg3 compound of ginseng may be useful for treating patients suffering with Alzheimer's disease.

Enhancement of neutral endopeptidase activity in SK-N-SH cells by ginsenoside Rb1.

OBJECTIVES: To investigate the effect of ginsenosides Rb1 and Rg1 on Neprilysin (NEP) activity in SK-N-SH cells, and probe the underlying mechanism. METHODS: The effects of ginsenosides Rb1 and Rg1 on NEP activity were analyzed by NEP peptidase assay. Western blot was used to determine NEP gene expression at translational level, and RT-PCR was also performed to detect NEP gene expression at transcriptional level. RESULTS: NEP peptidase assay indicated that ginsenoside Rb1 can improve the activity of NEP, and RT-PCR and western blot results showed that the enhancement of NEP activity by ginsenoside Rb1 was due to enhancing NEP gene expression, while Rg1 did not have this effect. CONCLUSION: Our studies showed that ginsenoside Rb1 can enhance NEP activity by upregulating NEP gene expression. Our findings might offer a pharmacological explanation for the use of ginseng in traditional medicine.

Regulation of zinc transporters by dietary flaxseed lignan in human breast cancer xenografts.

Zinc is essential for cell growth. Previous studies have shown that zinc concentration in breast cancer tissues is higher than that in normal breast tissues. Zinc cannot passively diffuse across cell membranes and specific zinc transporter proteins are required. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while ZIP transporters increase intracellular zinc. In this study, three human zinc transporter members: ZnT-1, ZIP2 and LIV-1 were chosen. We aimed to determine the effect of flaxseed lignan on the growth of ER-negative breast cancer cells in a nude mice model and observe the effect of flaxseed lignan on the regulation of the three zinc transporter in mRNA level. Nude mice were xenografted with human breast cancer cell line MDA-MB-231 and 6 weeks later were fed either the basal diet (BD) or BD supplemented with 10% FS and SDG for 5 weeks. The SDG levels were equivalent to the amounts in the 10% FS. RT-PCR was performed. Compared with the BD group, the tumor growth rate was significantly lower (P < 0. 05) in the FS and SDG group. ZnT-1 mRNA level in mammary tumor was increased in SDG group and decreased in FS group, but no significant difference was found. Extremely low amplification of ZIP2 from mRNA was detected, with no difference between the treatment groups. LIV-1 mRNA expression of SDG group increases compared with BD group. In FS group, it significantly increases nearly 9 times than that in BD group (P < 0. 005).

Regulation of zinc transporters by dietary zinc supplement in breast cancer.

Zinc is essential for cell growth and is a co-factor for more than 300 enzymes, representing over 50 different enzyme classes. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while ZIP transporters increase intracellular zinc. Previous studies have shown that zinc concentration in breast cancer tissues is higher than that in normal breast tissues. However, the mechanisms involved and the relations to zinc transporters are still unknown. A series of zinc transporters are characterized in this article and several of that are emphasized in view of their unique tissue-specific expressions. Established human breast cancer in a nude mice model is used. With a dietary zinc supplement treatment, ZnT-1 mRNA expression in established human breast cancer is raised by 24%, and is nearly 2 times of that in basal diet. ZIP1, ZIP2 and LIV-1 mRNA are the same between two treatment groups. Moreover, no significant changes of these zinc transporters expressions are found between differential breast cancer cell lines in the nude mice model. This is the first report, which detects the zinc transporters expressions in established human breast cancer in nude mice model. These results lead to the constitutive expression and response to zinc in different tissues. In addition to that, ZnT-1 seems to have played an important role in zinc homeostasis, even in breast cancer.