Epidemiological surveys show that folic acid can prevent prostate cancer, but fortified folic acid may increase the risk of the malignancy. The physician data queries from the National Cancer Institute of the USA describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the current literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide a clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for the trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains some conflicting epidemiologic evidence regarding folate and prostate cancer risk. However, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships.
Dietary Supplements ; adverse effects ; Disease Progression ; Folic Acid ; analogs & derivatives ; blood ; pharmacology ; Food, Fortified ; Humans ; Male ; Nutrition Surveys ; Nutritional Status ; Prostatic Neoplasms ; blood ; chemically induced

Abstract: Objective　To investigate the composition and diversity of midgut microbial community of Haemaphysalis longicornis infected with severe fever with thrombocytopenia syndrome virus (SFTSV)． Methods　The midgut DNA of three group Haemaphysalis longicornis infected with SFTSV was extracted, and the 16S rDNA gene of the sample was sequenced by HiSeq platform. The composition and diversity of endosymbiotic microbial community were clarified by OTU cluster analysis and alpha diversity analysis. Results　The midgut microbial clusters of the three groups infected with SFTSV were 143, 113, 163 OTUs respectively; the sparsity curve and abundance grade curve showed that the data had sufficient sequencing depth, and the midgut of Haemaphysalis longicornis infected with SFTSV was rich in microbial composition, but the species distribution was uneven. The analysis of microbial community composition showed that Proteobacteria, Firmicutes and Actinobacteria were the main dominant bacteria at the phyla level. At the class level, Gammaproteobacteria, Bacilli, Betaproteobacteria and Actinomycetia were the main dominant bacteria. At the order level, Legionellales, Bacillales, Burkholderiales and Actinomycetales were the main dominant orders. At the family level, Coxiellaceae, Bacillaceae, Moraxellaceae and Rhodococcaceae were the main dominant families. At the genus level, the relative abundance of Coxiella was the highest, followed by Aeribaillus and Azonexus. Alpha diversity analysis showed that the average Shannon index was 139.67, the average Simpson index was 0.48, the average Chao index was 145.06, and the average ACE index was 147.11. Conclusions　The species diversity of intestinal microorganisms in Haemaphysalis longicornis infected with SFTSV is rich. The results provide a basis for further exploring the interaction between intestinal microbes of Haemaphysalis longicornis and SFTSV and developing new ideas for the prevention and control of ticks and tick-borne diseases.

Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease and osteoporosis is one of its complications.

Objective To explore the relationship between fetal heart size and gestational weeks (GW). Methods The size of left atrium (LA), right atrium (RA), left ventricle (LV), right ventricle (RV), aorta (AO), pulmonary artery (PA), foramen ovale (FO), heart area (HA), thoracic area (TA), heart circumference (HC) and thoracic circumference (TC) were measured for 512 fetal hearts at 14-39 GW. The relationship between GW and the measurement was evaluated. Results The size of fetal heart chambers, AO, PA and ventricular septum (IVS) increased with the development of GW. The PA/AO, LA/RA, LV/RV, HC/TC and HA/TA were stable compared with different GW. Conclusion Fetal heart chambers increase with the development of GW. HA is correlated well with GW.

OBJECTIVETo observe the efficacy on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation so as to provide the effective clinical therapeutic methods for osteoporosis.

METHODSSixty cases of primary osteoporosis were randomized into a spreading moxibustion group (30 cases) and a calcium tablet group (30 cases). In the calcium tablet group, caltrate was prescribed for oral administration, 600 mg per day. In the spreading moxibustion group, on the basis of the treatment as the calcium tablet group, the spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming yang and activating blood circulation. The duration of treatment was 12 weeks. Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral density (BMD) were observed and compared before and after treatment in the patients between the two groups.

RESULTSVAS scores were reduced apparently after treatment in the two groups (both P < 0.01) and the results in the spreading moxibustion group were obviously superior to that in the calcium tablet group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion group were superior to those in the calcium tablet group (both P < 0.05). The total clinical effective rate was 86.67% (26/30) in the spreading moxibustion group, apparently better than 63.33% (19/30) in the calcium tablet group (P < 0.05). TCM clinical symptom scores after treatment were all reduced apparently in the two groups (both P < 0.01), and the result in the spreading moxibustion group was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82 +/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30) in the spreading moxibustion group, apparently better than 70.00% (21/30) in the calcium tablet group (P < 0.05).

CONCLUSIONThe combined therapy of spreading moxibustion for warming yang and activating blood circulation and the oral administration of caltrate apparently relieves pain and TCM clinical symptoms, improves BMD in the patients of osteoporosis and achieves definite clinical efficacy in the patients of osteoporosis.

Aged ; Blood Circulation ; Bone Density ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Osteoporosis ; physiopathology ; therapy ; Yang Deficiency ; physiopathology ; therapy

OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the inci-dence rate is the highest in all kinds of tumors in China. However,it remains unclear that how signifi-cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition. In this study, several kind of gastric cancer cell lines were used as the research object, and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer. METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823)by using glycolysis inhibitor, 2-deoxy-D-glucose(2-DG)and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR)and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences)to deter-mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells. In addition, western blot was used to detect the contribution of AMP-activated protein kinase (AMPK), and anti-apoptotic proteins(Bcl-2 and survivin)to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin. RESULTS In this study, it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L-1(MGC-803)to 15.57 mmol·L-1(BGC-823).MGC-803 was relatively sensitive to 2-DG (IC 50:3.28 mmol·L-1), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, MGC-803 could be more dependent on glycolysis than other cell lines, which was further confirmed by the fact that glucose (+)FCS(-)medium showed more growth and survival than glucose(-)FCS(+)medium.Alternatively, BGC-823, most resistant to 2-DG (IC50: 15.57 mmol·L- 1), was most sensitive to oligomycin, and showed more growth and survival in glucose(-)FCS(+)medium than in glucose(+)FCS(-)medium. Thus,we had reasons to think BGC-823 cells depended on oxidative phosphorylation for energy production. In BGC-823,AMPK,which is activated when ATP becomes limiting,was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented,which might result in resistance to 2-DG.Interestingly,AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in MGC-803,which is 2-DG sensitive. CONCLUSION There is a large metabolic difference between gastric cancer cell lines,which will facilitate the future gastric cancer therapy by targeting metabolic pathways.

OBJECTIVE To probe into the anti-esophagus cancer activity and mechanisms of DN3, a novel natural diterpenoid derivative. METHODS The anti-tumor activity in vitro of DN3 was evaluated by MTT, and by using human esophageal carcinoma cells xenografted into athymic mice model in vivo. The specific mechanisms of DN3, as a dual inhibitor of glycolysis and oxidative phos-phorylation(OXPHOS)were explored through cell and molecular biology techniques.For instance,the manner of cancer cell death induced by DN3 was characterized by hoechst33342, FITC-Annexin V/PI staining and flow cytometric analysis,then these changes of glucose consumption,glucose uptake and lactate production in glycolysis, as well as oxygen consumption rate (OCR) and ATP content in OXPHOS caused by DN3 were performed separately through related kits and SeahorseBioscience XF24 Extra-cellular Flux Analyzer.Furthermore,in order to obtain a clear understanding of the inhibition of DN3 to glycolysis and OXPHOS, these regulatory factors were investigated by Western blot, such as PI3K/AKT, c-Myc and p53 of glycolysis, Bax and HK2 of mitochondrial function. RESULTS DN3 inhibited the growth of esophagus cancer cell EC9706, EC109 and EC1 cells in a dose and time dependent manner,but showed no significant effects on human esophageal epithelial cells(HEECs).DN3 caused significant G2/M arrest of esophagus cancer cell lines and induced apoptosis of these cell lines, which indicated DN3 inhibited the growth of esophagus cancer cell through blocking cell cycle and inducing apoptosis in a dose and time-dependent manner. Importantly, 8 μM DN3 decreased the extracellular acidification rate (ECAR) by 45% in EC109, which indicated glycolysis was inhibited by DN3. Mean-while, DN3 decreased the oxygen consumption rate (OCR) and the OCR linked to intracellular ATP production in EC109 cells,but that was not obvious in HEECs,so which indicated that DN3 could selec-tively block OXPHOS of cancer cells. In addition, the accumulation of reactive oxygen species (ROS) and the drop of mitochondrial membrane potential (MMP) were also observed in EC109 incubated by DN3,which suggested mitochondrial biological function was disturbed.Furthermore,the expression of PI3K/AKT, c-Myc and HK2 related to glycolysis were down-regulated by DN3, but the p53 and Bax were up-regulated in esophageal carcinoma cells. The changes of these enzymes accounted for the decreased glycolysisand OXPHOS in esophageal carcinoma cells treated by DN3. CONCLUSION The new compound DN3 has a strong anti-esophageal carcinoma activity,and it is tolerable that DN3 is seen as a dual inhibitor of glycolysis and oxidative phosphorylation.

OBJECTIVE To study the anti-tumor activity and molecular mechanism of natural diter-pene derivative JD20 in vitro. METHODS Screening the sensitive of gastric carcinoma cell lines to JD20 by cytotoxicity test for 24 h.Cell morphology was evaluated by using DAPI.After staining of can-cer cells with PI or annexin V-FITC/PI respectively,the cell cycle and apoptosis induced by JD20 were detectded by flow cytometry. The change in cell membrane potential was detected by JC-1 test kit. Western blot method was used to detect the apoptosis-related protein. RESULTS The novel natural kaurane diterpene derivative JD20 had a significant inhibitory effect on tumor cells and was particularly active on gastric cancer cell lines HGC-27 (IC50=4.72 ± 1.37 μmol·L- 1) and MGC-803 (IC50=7.36 ± 0.86 μmol·L-1).Further studies found that JD20 resulted in thecell cycle arrest in the G2/M phase,and induced a significant apoptosis in HGC-27. In addition, JD20 also caused the drop of mitochondrial membrane potential of HGC-27 within a short time (3 h). Furthermore, the Western blotting analysis showed that JD20 could induce the up-regulation of p53,Bax and Bim protein expression in gastric can-cer cells,and the releasing of cytochrome c from the mitochondria into the cytoplasm,as well as the ac-tivation of casepase-9/3.CONCLUSION The natural kaurane diterpene derivative JD20 can inhibit the proliferation of various human cancer cells by blocking the cell cycle and inducing apoptosis, and its mechanism of inducing apoptosis may be related to the mitochondria-mediated apoptosis pathway.

OBJECTIVETo evaluate the effect of PKC-delta inhibitor Rottlerin on human colon cancer cells and its mechanism.

METHODSHuman colon cancer cell line SW1116 cells were treated with Rottlerin. The transcriptional level of DNA methyltransferase (Dnmt)1, Dnmt3a and Dnmt3b was detected by real-time RT-PCR. Cell cycle distribution was evaluated by flow cytometry (FCM). In addition, cellular morphological changes were examined by light microscopy.

RESULTSPKC-delta inhibitor decreased the expression of Dnmt1, Dnmt3a mRNA, up-regulated APC, p21(WAF1) and p16(INK4A) mRNA. Demonstarted by flow cytometry, Rottlerin increased the percentage of cell cycle G0/G1 phase cell numbers (P = 0.02) and decreased the percentage of cell cycle G2/M phase cell numbers (P = 0.01). Remarkable changes of cellular morphology were observed under light microscope: The volume and cytoplasm of cells treated with Rottlerin were increased. The cell contour was not very clear, and mitotic figures were less frequently seen.

CONCLUSIONPKC-delta inhibitor Rottlerin inhibites cell division and proliferation of the colon cancer SW1116 cells through regulating DNA methylation and blocking the signaling pathway of mitogen-activated protein kinase (MAPK).

Acetophenones ; pharmacology ; Adenomatous Polyposis Coli Protein ; genetics ; Benzopyrans ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Protein Kinase C-delta ; antagonists & inhibitors ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects

OBJECTIVETo study the teratogenicity of new high-energy compounds, 3, 4 two furazan-based oxidation furazan (DNTF) and the impact on human health, occupational exposure limits were provided for the following research.

METHODSPregnant SD rats were randomly divided into five groups by Standard teratogenicity test, including three dose groups (5.0, 15.8, 50.0 mg/kg), the negative control (vegetable oil), and the positive control group (CP 10.0 mg/kg). Each 10 to 15 rats were in one group. Gavage was consecutive for rats during pregnancy 7 ∼ 12 d and then sacrifice after 20 d.

RESULTSThere were no significantly difference between the three dose groups and negative controls in the pregnancy rate, the weight of pregnant rats, fetal weight, fetal growth, fetal malformation rate and internal organs,

CONCLUSIONThere were no maternal toxicity, embryo toxicity and teratogenicity for rats when DNTF in the range 5.0 ∼ 50.0 mg/kg.

Animals ; Female ; Nitrofurazone ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens