[Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study].

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1st September 2016 to 11th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) µmol/L, with (8.3±3.7) µmol/L in the preconception subgroup and (7.3±2.4) µmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (ß=-2.30, 95%CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (ß=-7.39, 95%CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (RR=1.05, 95%CI 1.01-1.08, P=0.002). Periconceptional vitamin B12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

[The mechanism of berberine on Methicillin resistant Staphylococcus aureus in vitro].

Objective: To explore the impact of traditional Chinese medicine berberine (BBR) on membrane integrity and permeability of Methicillin-resistant Staphylococcus aureus (MRSA) and the change of bacterial cell wall structure, laying a foundation for the clinical application of berberine in antibacterial. Methods: This study used a non-randomized concurrent controlled trial. The 3 MRSA strains were isolated and cultured from lower respiratory tract samples of geriatric patients from Shanghai Eighth People's Hospital between 2019 and 2020.The Meirier VETEK MS fully automated rapid microbial mass spectrometry detection system and VETEK 2 Compact fully automated microbial identification instrument were used to identify bacterial drug sensitivity experiments to detect bacterial species and drug sensitivity. The minimal inhibitory concentration (MIC) of BBR on MRSA strains was determined by broth microdilution. This study used conductivity tests to assess the changes in membrane permeability in response to different concentration of BBR on MRSA, while also investigating the changes in MRSA morphology by transmission electron microscopy. GraphPad Prism5 was used to analyze the differences in the electrical conductivity experimental results. Results: The MIC of BBR on MRSA was 64 µg/ml. After co-culturing MRSA with BBR for 4 h at 8 µg/ml, 16 µg/ml, 32 µg/ml, 64 µg/ml and 128 µg/ml, respectively, the electrical conductivity increased, compared with the control group, by 24.49%,34.59%,208.92%,196.40% and 208.68%, respectively. By transmission electron microscopy, This study found that low concentration of BBR (8 µg/ml,1/8 MIC) caused no significant damage to MRSA, and the bacterial structure of MRSA remained intact. The cell wall of MRSA became thinner after treatment with berberine at medium concentration (64 µg/ml,1 MIC), while high concentration of BBR (512 µg/ml,8 MIC) induced the destruction and dissolution of MRSA cell wall structure and the leakage of bacterial contents, leading to bacterial lysis. Conclusion: Berberine can kill bacteria by altering the permeability of MRSA cell membrane and destroying and dissolving the structure of the cell wall.

Plant protein diet-induced hypoimmunity by affecting the spiral valve intestinal microbiota and bile acid enterohepatic circulation in Amur sturgeon (Acipenser schrenckii).

An 8-week growth trial was conducted to study enterohepatic recirculation of bile acid metabolism and the intestinal microbiota of Amur sturgeon (Acipenser schrenckii) fed with three diets, including 540 g/kg, 270 g/kg or 0 g/kg fishmeal, which was correspondingly replaced by a plant protein blend (named P0, P50 and P100, respectively). The diets were designed to be isonitrogenous, isoenergetic and essential nutrients balanced. With rising levels of dietary plant protein, disruption of the spiral valve intestinal microbiota and more morbidity with liver disease were observed in the P100 group, although there were no haematological abnormalities observed. An obvious bile acids enterohepatic circulation disorder was found with phenotypes of increased liver bile acids compensatory synthesis, and reduced expression of bile acid receptors (FXR and TGR5), which induced BA accumulative toxicity. Accompanied by increased oxidative stress, it further induced hepatic lesions and hypoimmunity, which were non-negligible reasons for the high mortality and low utilization ability of plant protein by Amur sturgeon.

Association between Depressive Symptoms and Supplemental intake of Calcium and Vitamin D in Older Adults.

OBJECTIVES: We explored the associations between depressive symptoms and supplemental calcium and vitamin D intake in older adults. DESIGN: This was a prospective cohort study. PARTICIPANTS: 8,527 older adults aged ≥60 years from Zhejiang Major Public Health Surveillance Program (ZPHS) without depressive symptoms at baseline survey. MEASUREMENTS: Participants were divided into non-supplementation, calcium (Ca), vitamin D, and calcium plus vitamin D (CaD) groups based on their supplemental intake during the past year. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Binary logistic regression analyses were performed to examine the association between depressive symptoms and supplemental intake. RESULTS: When compared to the non-supplementation group, the Ca group exhibited a significant odds ratio (OR) of 0.731 (95% CI: 0.552-0.967, P=0.028). After adjusting for age, sex, and Ca food sources, the OR was even smaller for the CaD group (OR: 0.326; 95% CI: 0.119-0.889, P=0.029). Additionally, our results indicated that taking Ca supplements ≥4 days/week yielded a significant OR of 0.690 (95% CI: 0.492-0.968) after full adjustment. Taking CaD supplements ≥4 days/week yielded a significant OR of 0.282 (95% CI: 0.089-0.898) after adjusting for age, sex, and Ca food sources. CONCLUSIONS: Supplemental intake of Ca or CaD ≥4 days/week can decrease the risk of depressive symptoms in older adults, although CaD supplements may be more effective.

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

Effects of isomaltooligosaccharide and Bacillus supplementation on sow performance, serum metabolites, and serum and placental oxidative status.

This study investigated the effects of isomaltooligosaccharide (IMO) and Bacillus supplementation on sow performance, serum metabolites, and serum and placental oxidative status. Multiparous gestating sows (n = 130) with similar body conditions were randomly allocated to five groups (n = 26) receiving a basal diet (CON group) or a basal diet supplemented with 0.5% IMO (IMO group); 0.5% IMO and 0.02% Bacillus subtilis (IMO + S group); 0.5% IMO and 0.02% Bacillus licheniformis (IMO + L group); or 0.5% IMO, 0.02% Bacillus subtilis, and 0.02% Bacillus licheniformis (IMO + S+L group). There were no significant differences in the litter sizes among all dietary groups. The average piglet birth weight was improved in all treatment groups, and the placental efficiency was greater in the IMO + S and IMO + S+L groups than in the CON group (P < 0.05). The IMO + S+L group had increased the low-density lipoprotein cholesterol and reduced the total cholesterol in umbilical venous serum (P <  0.05). Additionally, the malondialdehyde concentrations were greater in umbilical venous serum of piglets in all treatment groups relative to that in the CON piglets (P <  0.05). The placental total antioxidant capacity was increased in the IMO+L and IMO+S+L groups (P <  0.05). Furthermore, the growth hormone concentration in umbilical venous serum was greater (P <  0.05) in all treatment groups. Overall, IMO and Bacillus supplementation during late gestation resulted in a changed metabolism of sows, improved the placental antioxidant capacity, and increased the growth hormone concentrations in umbilical venous serum, which ultimately improved the piglet birth weight and placental efficiency.

Dietary N-Carbamylglutamate (NCG) alleviates liver metabolic disease and hepatocyte apoptosis by suppressing ERK1/2-mTOR-S6K1 signal pathway via promoting endogenous arginine synthesis in Japanese seabass (Lateolabrax japonicus).

N-Carbamylglutamate (NCG), an analogue of N-acetylglutamate (NAG), can promote the synthesis of endogenous Arginine (Arg) in mammals, but not well studied in fish. This study was conducted to investigate the capacity of Arg endogenous synthesis by NCG, and the effects of various dietary NCG doses on growth performance, hepatic health and underlying nutrient regulation metabolism on ERK1/2-mTOR-S6K1 signaling pathway in Japanese seabass (Lateolabrax japonicus). Four experimental diets were prepared with NCG supplement levels of 0 (N0), 360 (N360), 720 (N720) and 3600 (N3600) mg/kg, in which N360 was at the maximum recommended level authorized by MOA, China in fish feed, and the N720 and N3600 levels were 2 and 10-fold of N360, respectively. Each diet was fed to 6 replicates with 30 Japanese seabass (initial body weight, IBW = 11.67 ±â€¯0.02 g) in each tank. The results showed that the dietary NCG supplementation had no significant effects on the SGR and morphometric parameters of Japanese seabass, but 360-720 mg/kg NCG inclusion promoted PPV, while the 10-fold (3600 mg/kg) overdose of NCG had remarkably negative effects with significantly reduced feed efficiency, PPV and LPV. We found that Japanese seabass can utilize 360-720 mg/kg NCG to synthesis Arg to improve the amino acid metabolism by increasing plasma Arg and up-regulating intestinal ASL gene expression. Increased plasma GST and decreased MDA indicated the improved antioxidant response. Dietary NCG inclusion decreased plasma IgM and down-regulated the mRNA levels of inflammation (TNF-α and IL8), apoptosis (caspase family) and fibrosis (TGF-ß1) related genes in the liver. The immunofluorescence examination revealed significantly decreased hepatic apoptosis and necrosis signals in the NCG groups. The ameliorated liver function and histological structure were closely related to the improved lipid metabolism parameters with decreased plasma VLDL and hepatic TG and NEFA accumulation, down-regulated fatty acid and cholesterol synthesis and simultaneously increased lipolysis gene mRNA levels, which regulated by inhibiting phosphorylation of ERK1/2-mTOR-S6K1 signaling pathway. Consuming 3600 mg/kg of dietary NCG is not safe for Japanese seabass culturing with the significantly increased FCR and decreased protein and lipid retention, and reduced plasma ALB. Accordingly, the observed efficacy and safety level of dietary NCG in the diet of Japanese seabass is 720 mg/kg.

[The doctors and their works on history of medicine in early Chinese Society of Medical History].

The Chinese Society of Medical History of the Chinese Medical Association is one of the most important organizations for the study of history of medicine in China. Many of its early members were both doctors and medical historians. Using the name list of this society in the Republic of China, along with other materials like medical journals and popular newspapers, the author tried to present a brief introduction of their achievements in modern medicine and contributions to the history of medicine. Also, it is the author's wish to attract attentions of more doctors of modern medicine to the study of history of medicine.

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway.

As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.

Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP)-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK) signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.

[Effect of prostate volume on the peripheral nerve block anesthesia in prostate biopsy].

OBJECTIVE: To evaluate the anesthetic efficacy of periprostatic nerve block in transrectal ultrasound(TRUS) guided biopsy on different prostate volume. METHODS: A total of 568 patients received prostate biopsy in Department of Urology, Subei People's Hospital from May 2013 to September 2015 were retrospectively studied. All patients were divided into local anesthesia group and nerve block group according to different way of anesthesia. Then each group was divided into four subgroups(20-40 ml, >40-60 ml, >60-100 ml and >100 ml subgroups) according to different prostate volume range. After being anaesthetized successfully, patients in two groups underwent prostate biopsy, visual analogue scale(VAS) scores, visual numeric scale(VNS)scores and complications were recorded and analyzed. At inter-group and intra-group in local anesthesia group and nerve block group, Mann-Whitney U test of non-parametric analysis and single factor variance analysis were used to compare the VAS scores and the VNS scores respectively, and chi-square test was used to compare the rates of complication. RESULTS: The VAS scores of four subgroups: local anesthesia group: 1.9±0.9, 2.8±1.5, 3.8±2.3 and 5.3±2.5; nerve block group: 1.5±0.7, 2.0±0.8, 2.9±1.7 and 4.2±2.0. The VNS scores: local anesthesia group: 3.4±0.6, 2.9±0.6, 2.7±0.5 and 1.6±0.7; nerve block group: 3.7±0.5, 3.3±0.4, 3.0±0.8 and 2.0±0.7. The VAS scores and the VNS scores had significant differences (Z=-3.637-98.253, all P<0.05) at inter-group or intra-group level. For the complication rates of operation, hematuria, blood, urinary retention were significant differences (F=1.347-15.402, all P<0.05) at intra-group level. But there were no significant differences at inter-group level(P>0.05). CONCLUSION: Compared with local anesthesia, ultrasound guided prostate peripheral nerve block anesthesia has great analgesic effect and high safety, but for patients with a large prostate volumethe analgesic effect is inefficiency.

Pharmacokinetics and ex-vivo pharmacodynamics of cefquinome against Klebsiella pneumonia in healthy dogs.

A two-period cross-over study was carried to investigate the pharmacokinetics (PK) and ex-vivo pharmacodynamics (PD) of cefquinome when administrated intravenously (IV) and intramuscularly (IM) in seven healthy dogs at a dose of 2 mg/kg of body weight. Serum concentrations were determined by HPLC-MS/MS assay and cefquinome concentration vs. time data after IV and IM were best fit to a two-compartment open model. Cefquinome mean values of area under concentration-time curve (AUC) were 5.15 µg · h/mL for IV dose and 4.59 µg · h/mL for IM dose. Distribution half-lives and elimination half-lives after IV dose and IM dose were 0.27 and 0.44 h, 1.53 and 1.94 h, respectively. Values of total body clearance (ClB ) and volume of distribution at steady-state (Vss ) were 0.49 L · kg/h and 0.81 L/kg, respectively. After IM dose, Cmax was 2.53 µg/mL and the bioavailability was 89.13%. For PD profile, the determined MIC and MBC values against K. pneumonia were 0.030 and 0.060 µg/mL in MHB and 0.032 and 0.064 µg/mL in serum. The ex vivo time-kill curves also were established in serum. In conjunction with the data on MIC, MBC values and the ex vivo bactericidal activity in serum, the present results allowed prediction that a single cefquinome dosage of 2 mg/kg may be effective in dogs against K. pneumonia infection.

The sodium-activated potassium channel Slack is modulated by hypercapnia and acidosis.

Slack (Slo 2.2), a member of the Slo potassium channel family, is activated by both voltage and cytosolic factors, such as Na(+) ([Na(+)](i)) and Cl(-) ([Cl(-)](i)). Since the Slo family is known to play a role in hypoxia, and since hypoxia/ischemia is associated with an increase in H(+) and CO(2) intracellularly, we hypothesized that the Slack channel may be affected by changes in intracellular concentrations of CO(2) and H(+). To examine this, we expressed the Slack channel in Xenopus oocytes and the Slo 2.2 protein was allowed to be inserted into the plasma membrane. Inside-out patch recordings were performed to examine the response of Slack to different CO(2) concentrations (0.038%, 5%, 12%) and to different pH levels (6.3, 6.8, 7.3, 7.8, 8.3). In the presence of low [Na(+)](i) (5 mM), the Slack channel open probability decreased when exposed to decreased pH or increased CO(2) in a dose-dependent fashion (from 0.28+/-0.03, n=3, at pH 7.3 to 0.006+/-0.005, n=3, P=0.0004, at pH 6.8; and from 0.65+/-0.17, n=3, at 0.038% CO(2) to 0.22+/-0.07, n=3, P=0.04 at 12% CO(2)). In the presence of high [Na(+)](i) (45 mM), Slack open probability increased (from 0.03+/-0.01 at 5 mM [Na(+)](i), n=3, to 0.11+/-0.01, n=3, P=0.01) even in the presence of decreased pH (6.3). Since Slack activity increases significantly when exposed to increased [Na(+)](i), even in presence of increased H(+), we propose that Slack may play an important role in pathological conditions during which there is an increase in the intracellular concentrations of both acid and Na(+), such as in ischemia/hypoxia.

In vitro evaluation of concurrent use of commercially available insect repellent and sunscreen preparations.

BACKGROUND: Insect repellents and sunscreens are over-the-counter products extensively used by the general public. Concurrent application of these products has become widespread in many regions across North America, because of concerns about West Nile virus and skin cancers. OBJECTIVES: We investigated whether formulation type, application amount, and sequence would affect the percutaneous absorption profiles of the active repellent and sunscreen ingredients. METHODS: In vitro percutaneous permeation of the repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone from concurrent application of five commercially available products (A, repellent spray; B, repellent lotion; C, sunscreen lotion; D and E, combined repellent/sunscreen lotions) was measured and compared using Franz-style diffusion cells with piglet skin at 37 degrees C. RESULTS: Penetration of DEET in A and B increased by 1640% and 282%, respectively, when C was applied concurrently. Penetration of DEET in D and E was 53% and 79% higher than that in B. Permeation of DEET from A + C (2:1) and A + C (1: 2) increased by 530% and 278%, respectively. Permeation of oxybenzone was 189% and 280% higher in A + C and B + C than in C. Permeation of oxybenzone in D and E was also 221% and 296% higher than that in C. Permeation of oxybenzone was 196% greater when A was applied on top of C than when C was applied on top of A, while oxybenzone in A + C (1:2) permeated 171% more than that in A + C (2:1). CONCLUSIONS: Concurrent application of commercially available repellent and sunscreen products resulted in significant synergistic percutaneous permeation of the repellent DEET and the sunscreen oxybenzone in vitro. The percutaneous penetration profiles were dependent upon the type of formulation, application sequence and application proportion.

Determination of scopolamine, atropine and anisodamine in Flos daturae by capillary electrophoresis.

A capillary electrophoresis method was developed for the separation and determination of tropane alkaloids in Flos daturae plants. Separation was performed on a fused silica capillary(42.1 cm x 50 microm i.d.) at an applied voltage of 20 kV. Scopolamine, atropine and anisodamine were well separated in the buffer of 50 mmol/L phosphate buffer (pH 5.0) containing 20% (v/v) tetrahydrofuran (THF). Beer's law was obeyed in the range of concentration of 2.4-21.8 microg/mL for scopolamine, 4.0-36.0 microg/mL for atropine and 2.6-23.7 microg/mL for anisodamine, respectively, and the correlation coefficients were over 0.999 (n = 6). The developed method was applied for the analysis of herb samples.

Identification of IgE-binding proteins in soy lecithin.

BACKGROUND: Soy lecithin is widely used as an emulsifier in processed foods, pharmaceuticals and cosmetics. Soy lecithin is composed principally of phospholipids; however, it has also been shown to contain IgE-binding proteins, albeit at a low level. A few clinical cases involving allergic reactions to soy lecithin have been reported. The purpose of this investigation is to better characterize the IgE-binding proteins typically found in lecithin. METHODS: Soy lecithin proteins were isolated following solvent extraction of lipid components and then separated on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The separated lecithin proteins were immunoblotted with sera from soy-sensitive individuals to determine the pattern of IgE-binding proteins. The identity of IgE-reactive bands was determined from their N-terminal sequence. RESULTS: The level of protein in six lecithin samples obtained from commercial suppliers ranged from 100 to 1,400 ppm. Lecithin samples showed similar protein patterns when examined by SDS-PAGE. Immunoblotting with sera from soy-sensitive individuals showed IgE binding to bands corresponding to 7, 12, 20, 39 and 57 kD. N-terminal analysis of these IgE-binding bands resulted in sequences for 3 components. The 12-kD band was identified as a methionine-rich protein (MRP) and a member of the 2S albumin class of soy proteins. The 20-kD band was found to be soybean Kunitz trypsin inhibitor. The 39-kD band was matched to a soy protein with unknown function. CONCLUSIONS: Soy lecithin contains a number of IgE-binding proteins; thus, it might represent a source of hidden allergens. These allergens are a more significant concern for soy-allergic individuals consuming lecithin products as a health supplement. In addition, the MRP and the 39-kD protein identified in this study represent newly identified IgE-binding proteins.

Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter.

A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of beta-CIT (19), the fluoroethyl ester of beta-CIT (20), the N-fluoropropyl derivative of beta-CBT (12), and the fluoropropyl ester of beta-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of (18)F-labeled PET imaging agents for the DAT.

Tel-2 is a novel transcriptional repressor related to the Ets factor Tel/ETV-6.

We report here the isolation of Tel-2, a novel member of the Ets transcription factor family, with high homology to Tel/ETV-6. Tel-2 is the second mammalian member of the Tel Ets family subclass whose prototype Tel is involved in various chromosomal translocations in human cancers. Six differentially expressed alternative splice products of Tel-2 were characterized encoding different Tel-2 isoforms which either contain or lack the amino-terminal Pointed domain and also vary at the carboxyl terminus. In contrast to Tel, which is highly expressed in several different cell types and tissues, Tel-2 is only weakly expressed in a variety of tissues and cell types, including placenta, prostate, spleen, liver, and lung. Tel-2 binds to functionally relevant Ets-binding sites of several genes and only the Tel-2 isoform containing the Pointed domain and the DNA-binding domain acts as a strong repressor of transcription. The retinoic acid receptor alpha and bone morphogenetic protein-6B (BMP-6) genes are specifically repressed by Tel-2 indicating a function for Tel-2 as an inhibitor of differentiation. Due to the important involvement of Tel in human cancer and the location of Tel-2 within the MHC cluster region, Tel-2 might be involved in chromosomal translocations in human cancer as well.

Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

Approximately 60% of breast cancer patients have hormone-dependent breast cancer containing estrogen receptors and requiring estrogen for tumor growth. The extent of estrogen biosynthesis and metabolism in the breast cancer tissue microenvironment influences breast-tumor development and growth, and endogenous and exogenous agents may alter the levels of hormonally active estrogens and their metabolites. Isoflavonoid phytoestrogens such as genistein exhibit numerous biochemical activities; however, their effects on estrogen biosynthesis and metabolism in breast cancer cells have not been fully examined. MCF-7 cells (hormone-dependent) and MBA-MB-231 cells (hormone-independent) were treated with genistein (100 nM) for five days and then incubated with radiolabeled estradiol (100 nM, 2.5 microCi) for 0 to 48 h. Media were extracted with ethyl acetate, and the organic residues analyzed by reverse-phase HPLC with a radioactivity flow detector. The major metabolite formed in all cases is estrone, although differences were observed between the cell lines and the various drug treatments. The formation of estrone in untreated MCF-7 cells (approximately 9.3% of radioactivity at 24 h) is relatively limited, in contrast to untreated MDA-MB-231 cells (approximately 32.0% of radioactivity at 24 h). Treatment of MCF-7 cells with 100 nM genistein increased the conversion of estradiol to estrone up to 19.5% in 24 h. The effect of genistein on estrone formation in MDA-MB-231 cells resulted in 37.7% of the radioactivity being estrone. Thus, genistein treatment of breast cancer cells resulted in increased 17-betahydroxysteroid dehydrogenase activity and elevated formation of estrone. Increased levels of oxidative 17-betahydroxysteroid dehydrogenase activity (Type II) were confirmed by Western blots. Therefore, exposure of breast cancer cells to genistein results in elevated conversion of estradiol to estrogenically weaker or inactive metabolites. The regulation of breast-tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

[Studies on chemical constituents from Euphorbia fischeriana Steud].

OBJECTIVE: To study the chemical constituents of ethanol extract from dried roots of Euphorbia fischeriana. METHOD: Compounds were separated by column chromatography with silca gel and elucidated by chemical evidence and spectral analysis. RESULT: Isobauerenyl acetate, beta-amyrin acetate, 24-methylenecycloartenone,octacosyl ferulate and 2,4-dihydroxy-6-methoxy-3-methyl acetophenone were isolated and elucidated. CONCLUSION: All the compounds were isolated from the plant for the first time.