Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival

There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2 independent] can be derived from mouse embryonic stem (ES) cells in vitro and from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the E8.5 neural plate and persist throughout life. Primitive NSCs give rise to definitive NSCs. Loss and gain of functions were used to study the role of vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs were increased because of the enhanced survival of primitive NSCs. In contrast, neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive NSCs numbers were decreased because of the enhanced cell death of definitive NSCs. These effects were not observed in cells lacking Flt1, another VEGF receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc-soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A phenotypes also were blocked by inhibition of the downstream effector nuclear factor kappa B (NF-kappa B). Thus, both the cell death of primitive NSC and the cell survival of definitive NSC induced by VEGF-A stimulation are mediated by bifunctional NF-kappa B effects. In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically

In vitro antischistosomal activity of Artemisia annua and Artemisia afra extracts

Background Schistosomiasis, a neglected tropical disease, imposes substantial health and economic burdens on impoverished groups living in predominantly rural areas. Praziquantel (PZQ) is the only drug available for treatment, and it is not completely efficacious. Artemisia annua and Artemisia afra infusions were proposed to possess antischistosomal activities in a recently retracted publication of a clinical trial, leading to our investigation in vitro. Objective The objective was to identify the main components of the infusions and evaluate the in vitro antischistosomal activities of traditionally prepared infusions as well as hexane and dichloromethane (DCM) extracts of the infusions of A. afra and A. annua. Methods Infusions of A. afra and A. annua were submitted to liquid-liquid partitioning with n-hexane and DCM to provide samples for in vitro bioassays using newly transformed schistosomulas (NTS) and adult Schistosoma mansoni worms obtained from infected mice. The viability of the NTS and adult S. mansoni was visually scored via microscopic readout. Results Nine phytochemicals comprising coumarins and organic acids were identified. A. afra and A. annua infusions and extracts possess potent in vitro antischistosomal activities against NTS, at 100 μg/ml. However, the A. afra infusions exhibited better activities against NTS than the A. annua infusion. The A. afra hexane- and DCM extracts presented IC50 values that are similar to PZQ (1.5 μg/ml) and approximately five times lower than the comparison drug artesunate (11.6 μg/ml) against NTS. Low IC50 values for both these extracts were also obtained in phenotypic assays with adult S. mansoni. Conclusion A. afra shows greater antischistosomal potential than A. annua. Thus, further studies are necessary to identify the active molecule(s) responsible for the notable antischistosomal activity of A. afra

Ionospheric quasi-static electric field anomalies during seismic activity in August–September 1981

The paper proposes new results, analyses and information for the plate tectonic situation in the processing of INTERCOSMOS-BULGARIA-1300 satellite data about anomalies of the quasi-static electric field in the upper ionosphere over activated earthquake source regions at different latitudes. The earthquake catalogue is made on the basis of information from the United State Geological Survey (USGS) website. The disturbances in ionospheric quasi-static electric fields are recorded by IESP-1 instrument aboard the INTERCOSMOS-BULGARIA-1300 satellite and they are compared with significant seismic events from the period 14 August–20 September 1981 in magnetically very quiet, quiet and medium quiet days. The main tectonic characteristics of the seismically activated territories are also taken in account. The main goal of the above research work is to enlarge the research of possible connections between anomalous vertical electric field penetrations into the ionosphere and the earthquake manifestations, also to propose tectonic arguments for the observed phenomena. The studies are represented in four main blocks: (i) previous studies of similar problems, (ii) selection of satellite, seismic and plate tectonic data, (iii) data processing with new specialized software and observations of the quasi-static electric field and (iiii) summary, comparison of new with previous results in our studies and conclusion. We establish the high informativity of the vertical component <i>Ez</i> of the quasi-static electric field in the upper ionosphere according observations by INTERCOSMOS-BULGARIA-1300 that are placed above considerably activated earthquake sources. This component shows an increase of about 2–10 mV/m above sources, situated on mobile structures of the plates. The paper discusses the observed effects. It is represented also a statistical study of ionospheric effects 5–15 days before and 5–15 days after the earthquakes with magnitude M 4.8–7.9

Breast cancer risk among first-generation migrants in the Netherlands

We investigated breast cancer incidence in migrants in the Netherlands in 1988-1998. The standardised incidence ratio for breast cancer in Northwest-Netherlands was statistically significantly reduced for women born in Surinam (0.56), Turkey (0.29) and Morocco (0.22). The proportion of women with advanced stages (III and IV) did not differ significantly between migrants and women born in the Netherlands

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

Background: Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results: Mice drank a 10% ethanol so

Fetal and post-natal outcomes in offspring after intrauterine metformin exposure:A systematic review and meta-analysis of animal experiments

Aims: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. Methods: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. Results: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. Conclusion: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.</p

Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial

Objectives To study the effects of metformin on the incidence of vitamin B-12 deficiency (<150 pmol/l), low concentrations of vitamin B-12 (150-220 pmol/l), and folate and homocysteine concentrations in patients with type 2 diabetes receiving treatment with insulin