Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics.

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8-7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25-100 µg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.

Sex difference in stress-induced enhancement of hippocampal CA1 long-term depression during puberty.

Females and males react differently to stress. Our previous studies revealed that acute stress facilitates the induction of long-term depression (LTD) in hippocampal CA1 region. However, it remains unknown whether sex difference exists in the effect of stress on LTD. Using an acute unpredictable and inescapable restraint-tailshock stress paradigm, we report here that hippocampal slices from stressed male rats expressed larger LTD by low-frequency stimulation (LFS) than controls, whereas such effect was not observed in female rats during puberty. The facilitatory effect of stress on LTD was prevented when animals were submitted to bilateral adrenalectomy. However, no sex difference in the magnitudes of LTD induced by direct application of N-methy-D-aspartate or a combination of LFS with the glutamate uptake inhibitor D,L-threo-ß-benzyloxyaspartate was observed in slices from naive rats. Female rats exhibited significantly higher basal but not stress-evoked levels of plasma corticosterone than male rats. In addition, the expression levels of glucocorticoid receptors in hippocampal CA1 region were significantly lower in female than male rats. Moreover, female rats showed less responsiveness to stress- or dexamethasone-induced suppression of glutamate uptake in hippocampal synaptosomal preparations than male rats. Importantly, female rats that were masculinized with testosterone at birth responded to stress like male rats did, demonstrating an enhancement of LTD. In contrast, ovariectomized female rats failed to restore the ability of stress to facilitate LTD. These results reveal an obvious sex difference in stress-induced modification of hippocampal synaptic plasticity, which depends on organizational effect of testosterone during early development.

Bioavailability Assessment of Heavy Metals Using Various Multi-Element Extractants in an Indigenous Zinc Smelting Contaminated Site, Southwestern China.

Despite recent studies have investigated the strong influences of smelting activities on heavy metal contamination in the soil environment, little studies have been conducted on the current information about the potential environmental risks posed by toxic heavy metals in smelting contaminated sites. In the present study, a combination of the bioavailability, speciation, and release kinetics of toxic heavy metals in the indigenous zinc smelting contaminated soil were reliably used as an effective tool to support site risk assessment. The bioavailability results revealed that the bioavailable metal concentrations were intrinsically dependent on the types of chemical extractants. Interestingly, 0.02 mol/L EDTA + 0.5 mol/L CH3COONH4 was found to be the best extractant, which extracted 30.21% of Cu, 31.54% of Mn, 2.39% of Ni and 28.89% of Zn, respectively. The sequential extraction results suggested that Cd, Pb, and Zn were the most mobile elements, which would pose the potential risks to the environment. The correlation of metal bioavailability with their fractionation implied that the exchangeable metal fractions were easily extracted by CaCl2 and Mehlich 1, while the carbonate and organic bound metal fractions could be extracted by EDTA and DTPA with stronger chelating ability. Moreover, the kinetic modeling results suggested that the chemical desorption mechanism might be the major factor controlling heavy metal release. These results could provide some valuable references for the risk assessment and management of heavy metals in the smelting contaminated sites.

Preparation and Evaluation of New Glycopeptides Obtained by Proteolysis from Corn Gluten Meal Followed by Transglutaminase-Induced Glycosylation with Glucosamine.

New glycopeptides were generated by proteolysis from corn gluten meal (CGM) followed by transglutaminase (TGase)-induced glycosylation with glucosamine (GlcN). The glycopeptides exhibited desirable antioxidant and intracellular ROS-scavenging properties. The amount of conjugated GlcN quantified by high-performance liquid chromatography (HPLC) was 23.0 g/kg protein. The formed glycopeptides contained both glycosylated and glycation types, as demonstrated by the electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS/MS). The glycopeptides exhibited scavenging capabilities against free radical diphenylpicrylhydrazyl (DPPH) and hydroxyl radicals by reducing their power. The potential protection of glycopeptides against ethanol-induced injury in LO2 cells was assessed In Vitro based on methyl thiazole tetrazolium (MTT) testing and intracellular reactive oxygen species (ROS) scavenging capacity, respectively. Glycopeptide cytoprotection was expressed in a dose-dependent manner, with the glycopeptides exhibiting good solubility ranging from 74.8% to 83.2% throughout a pH range of 2-10. Correspondingly, the glycopeptides showed good emulsifying activity (36.0 m2/g protein), emulsion stability (74.9%), and low surface hydrophobicity (16.3). These results indicate that glycosylation of CGM significantly improved its biological and functional properties. Glycopeptides from CGM could be used as potential antioxidants as well as comprising a functional food ingredient.

Unusual patterns of neural tube defects in a high risk region of northern China.

OBJECTIVE: To study the prevalence of different types of neural tube defects (NTDs) in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns. METHODS: A surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province. RESULTS: The results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China. CONCLUSION: The prevalence of NTDs is associated with its patterns.

Selective deletion of PPARß/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARß/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARß/δ in the fibroblast (FSPCre-Pparb/d-/-) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 (Lrg1), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of Lrg1 by PPARß/δ in fibroblasts is an important signaling conduit integrating PPARß/δ and TGFß1-signaling networks in skin health and disease. Thus, the FSPCre-Pparb/d-/- mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.

Intrauterine infections and birth defects.

Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.

[Epidemiology of birth defects in high-prevalence areas of China].

OBJECTIVE: To study the levels of prevalence and to describe the epidemiological features of birth defects in high-prevalence areas in China. METHODS: A population-based retrospective study was conducted in two counties of Shanxi province that including birth defects among fetuses and live births born after 20 weeks' gestational age in the study areas from 2002 through 2004. RESULTS: During 2002 - 2004, the prevalence of birth defects was 844.2 per 10 000 births in study areas and the first five main birth defects were inguinal hernia (182.2 per 10,000 births), anencephaly (104.4 per 10 000 births), congenital mental retardation (79.4 per 10,000 births), congenital heart diseases (73.2 per 10,000 births) and spina bifida (63.9 per 10,000 births). These five main birth defects accounted for about 60% of total birth defect cases. Inguinal hernia, undescended testicle, congenital mental retardation were usually not included for statistical analysis on birth defect. Excluding these birth defects, the prevalence of birth defects in study areas was 537.2 per 10,000 births and the first five main birth defects were anencephaly, congenital heart diseases, spina bifida, hydrocephaly (40.5 per 10 000 births) and encephalocele (31.2 per 10 000 births). The male prevalence of birth defects was 966.2 per 10 000 births, which was significantly higher than prevalence in females. The prevalence rates of birth defects for maternal age groups under 20 years old and over 30 years old were remarkably higher than those for 20-24 year and 25-29 year old mothers. The teenage mothers were at higher risk of having a child with neural tube defects(NTDs) or congenital heart diseases. Prevalence rates under 20 year maternal age group were 408.8 and 188.7 per 10 000 births for NTDs and congenital heart diseases respectively, whereas corresponding rates were 204.8 and 91.0 per 10 000 births for groups over 30 years of age. The prevalence rates increased with increasing gravidity or parity. CONCLUSION: This study showed that the patterns of birth defects in study areas were very different from those of other areas, with an unusually high prevalence of NTDs. The study also suggested that both young and advanced mothers were at increased risk of having a child with a birth defect.

[Capacity of monitoring system on birth defects during 1990s in China].

OBJECTIVE: To understand the status and capacity of monitoring system on birth defects in China. METHODS: Data regarding 27 groups of birth defects from 57 monitoring programs in World Atlas of Birth Defects (2nd Edition) published by WHO/ICBDMS/EUROCAT/HGP and descriptive analysis by their ranking and contribution were carried out. RESULTS: Both hospital-based (Chinese Birth Defects Monitoring Network, CBDMN) and population-based (Birth Defect Surveillance System in Thirty Counties of Four Provinces, Beijing) monitoring systems showed the same characteristics as below: (1) Not enough groups were monitored, with trisomy 13/18 and congenital heart disease not reported. (2) Prevalence on those 'easily observed' group was high and cleft lip with or without cleft palate in CBDMN ranked 5 among 57 programs, with similar situation in polydactyly. (3) While prevalence rates of internal system and choromosal anomaly were low, CBDMN ranked 56 with Beijing the only non-reported city among all the 57 programs. (4) Unreasonable relationship was seen with prevalence of cleft lip was 5.76,4.02 times higher than that of cleft palate in CBDMN and in Beijing program. Which was 1.58 times of the world's means. Prevalence rates of anencephaly and total anotia/microtia rose 10.39% while spina bifida, hydrocephaly, and gastroschisis had a 4%-5% increase. The prevalence of hypospadias decreased by 4.13% and Down syndrome by 3.02%. CONCLUSION: The capacity of birth defects monitoring, both hospital-based and population-based, was poor in the 1990s, in China.

[Study on the risk factors of 100 cases with vulvar dystrophy].

OBJECTIVE: To assess the risk factors for vulvar dystrophy. METHODS: An epidemiological study was carried out. Data on 100 cases with vulvar dystrophy was reviewed and face to face interviewed with a uniform questionnaire including the manner of work, environmental temperature, habit of eating, mood, underwear wearing, autoimmune diseases, marriage, menstrual age, the quantity of menses, orders of pregnancy, and labor trauma of vulvar during delivery, vulvitis and urethritis ect. Univariable analysis and multivariate logistic regression analysis were carried out with 1:1 case-control methodology. RESULTS: Multiple conditional logistic regression analysis showed that vulvar dystrophy was positively associated with hot food (OR = 2.55, 95% CI: 1.24 - 5.25), mood (OR = 4.27, 95% CI: 1.96 - 9.29), order of pregnancy (OR = 3.37, 95% CI: 2.11 - 5.40), vulvitis (OR = 6.74, 95% CI: 2.66 - 17.09) and urethritis (OR = 11.02, 95% CI: 1.01 - 120.19). Vulviitis or urethritis increased 6.74 or 11.02 times the incidence of vulva dystrophy. Anger or nervous state contributed to the incidence of vulva dystrophy (OR = 4.27). Addict to hot food and order of labor also increased risk ratio for 2.55 and 3.37 times, respectively. CONCLUSION: The risk factors of vulvar dystrophy were: addict to hot food, often holding a angry or nervous state, increase of labors, having vulvitis and urethritis.