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Folic acid (FA) is a synthetic and highly stable version of folate, while 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). The current study aims to evaluate the toxicity and safety of FA and MTHF-Ca on embryonic development, with a focus on cardiovascular defects. We began to analyze the toxicity of FA and MTHF-Ca in zebrafish from four to seventy-two hours postfertilization and assessed the efficacy of FA and MTHF-Ca in a zebrafish angiogenesis model. We then analyzed the differently expressed genes in in vitro fertilized murine blastocysts cultured with FA and MTHF-Ca. By using gene-expression profiling, we identified a novel gene in mice that encodes an essential eukaryotic translation initiation factor (Eif1ad7). We further applied the morpholino-mediated gene-knockdown approach to explore whether the FA inhibition of this gene (eif1axb in zebrafish) caused cardiac development disorders, which we confirmed with qRT-PCR. We found that FA, but not MTHF-Ca, could inhibit angiogenesis in zebrafish and result in abnormal cardiovascular development, leading to embryonic death owing to the downregulation of eif1axb. MTHF-Ca, however, had no such cardiotoxicity, unlike FA. The current study thereby provides experimental evidence that FA, rather than MTHF-Ca, has cardiovascular toxicity in early embryonic development and suggests that excessive supplementation of FA in perinatal women may be related to the potential risk of cardiovascular disorders, such as congenital heart disease. [ABSTRACT FROM AUTHOR]

Qu‐feng‐sheng‐shi Granules (QFSSG), a common prescription for the treatment of chronic inflammation and allergic rhinitis, is widely used in the clinic as a traditional Chinese medicine. Chemical analysis and quality control studies of this formulation are relatively limited compared with pharmacological studies. In this study, a high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (HPLC–ESI–Q/TOF–MSn) was used to identify the components in this prescription. Next, to quantify six major compounds, an HPLC–UV method was developed and validated. The results showed that 53 compounds were identified based on the MSn data, retention time and previous reports, including 17 coumarins, 14 lignans, 10 chromones, nine phenylethanoid glycosides and three other compounds, were identified or tentatively assigned. Contents of six major bioactive compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, magnolin, imperatorin, isoimperatorin) could be determined by HPLC simultaneously. In addition, the potential anti‐inflammatory activity of six major compounds was determined too, and we found that four compounds (4′‐O‐β‐glucopyranosyl‐5‐O‐methylvisamminol, Prim‐O‐glucosylcimifugin, forsythin, imperatorin) have a potent nitric oxide inhibitory effect. In conclusion, this work provided comprehensive information on the quality control of QFSSG and evaluated the potential biological activity of the main components in QFSSG, which can contribute to understanding and using it more scientifically. [ABSTRACT FROM AUTHOR]

Targeted drug delivery could increase the efficacy of chemotherapy, however, a plethora of obstacles exist in the current targeted delivery designs. In this study, we introduce a novel avenue of targeted drug delivery using electro-acupuncture and evaluate its effect on the distribution of paclitaxel in a breast cancer mouse model. Our results show that electro-acupuncture intervention significantly increased the intratumoral concentration of paclitaxel. The mice in acupuncture group showed shorter t max, longer t 1/2 and higher AUC of paclitaxel as compared with that in paclitaxel-only group. Moreover, we found that the acupuncture intervention significantly induced cell apoptosis in tumors. The levels of COL IV and α-SMA increased in tumors of acupuncture group. The negative tumor metastasis biomarker, NM23, was significantly upregulated in tumors of mice in acupuncture group. Our results suggest that acupuncture intervention around the tumor area increases the local concentration of chemotherapeutic agents. The targeted effect of acupuncture is achieved by altering tumor microvasculature and microenvironment. Therefore, combined therapy of acupuncture with chemotherapeutic agents is promising in improving cancer treatment efficacy. [ABSTRACT FROM AUTHOR]

We previously reported the special herbal complex (Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix) suppressed telomerase activity in chemo-endocrine-resistant cancer cell lines. The present study attempted to determine whether the above herbal complex induces apoptosis in endocrine-resistant AN3CA and adriamycin-resistant MCF7/ADR carcinoma cells. Exposure to the herbal complex decreased cell viability in a time- and dose-dependent manner in the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The agent induced cellular apoptosis was determined by DNA fragmentation and a nuclear staining assay. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed the decreased expression of apoptosis-related genes, bcl-2, c-myc and human telomerase catalytic subunit (hTERT). A decreased protein level of bcl-2 and c-myc was also determined by Western blot analysis. The data imply that the decreased expression of the genes via suppressing telomerase activity is involved in cellular apoptosis in endocrine-resistant AN3CA cells. Thus, it is suggested that the special herbal complex may be a promising candidate for the treatment of endocrine-resistant gynecologic carcinomas. [Copyright &y& Elsevier]

We have found that Juzen-taiho-to has a preventive effect on endometrial carcinogenesis in mice (Carcinogenesis 22 (2001) 587). In the present study, the constituents of Juzen-taiho-to responsible for this effect were explored using a short-term experiment. Thirty female ICR mice were divided into five groups: Group 1 was given a diet containing 0.2% of Juzen-taiho-to and 5 ppm estradiol-17β (E2); Group 2 was given a diet containing Shimotsu-to (0.07%) and E2 (5 ppm); Group 3 received Shikunshi-to (0.08%) and E2 (5 ppm) in the diet; Group 4 was given 5 ppm E2 in the diet; and Group 5 served as a control. Exposure of Juzen-taiho-to or Shimotsu-to decreased E2-stimulated expression of estrogen-related gene c-fos mRNA (P<0.05), and the cytokines interleukin-1α mRNA and tumor necrosis factor α mRNA P<0.01). A similar trend was not found upon treatment with Shikunshi-to. These findings suggest that Shimotsu-to is responsible for the inhibitory effects of Juzen-taiho-to on the estrogen-related endometrial carcinogenesis in mice. [Copyright &y& Elsevier]

Folate is a vitamin beneficial for humans that plays an important role in metabolism, but it cannot be well supplemented by food; it is necessary to supplement it in other ways. Based on this consideration, a novel crystal form C of 6S-5-methyltetrahydrofolate calcium salt (MTHF CAC) was obtained. To explore the difference between MTHF CAC and the crystal form Ⅰ of 6S-5-methyltetrahydrofolate calcium salt (MTHF CA) as well as an amorphous product of 6S-5-methyltetrahydrofolate glucosamine salt (MTHF GA), their stability and pharmacokinetic behaviours were compared. The results of high-performance liquid chromatography coupled with ultraviolet detection analysis indicated that MTHF CAC showed a better stability than MTHF CA and MTHF GA. After oral administration of MTHF CAC, MTHF CA, and MTHF GA to male rats, the MTHF concentrations were analysed using a validated liquid chromatography–tandem mass spectrometry, and the pharmacokinetic parameters were compared. The mean residence times (0–t) of MTHF CAC, MTHF CA, and MTHF GA were 3.7 ± 1.9 h, 1.0 ± 0.2 h (p < 0.01), and 1.5 ± 0.3 h (p < 0.05), respectively. The relative bioavailability of MTHF CAC was calculated to be 351% and 218% compared with MTHF CA and MTHF GA, respectively, which suggests that MTHF CAC can be better absorbed and utilized for a longer period of time. [ABSTRACT FROM AUTHOR]

Examines the activity of the ribonucleoprotein telomerase in a dissociated cell culture of the endometrium. Comparison of telomerase activity in epithelial and stromal cells; Association of telomerase activity with the proliferative activity.