Human Wharton�s jelly-derived mesenchymal stem cells express oocyte developmental genes during co-culture with placental cells

Objective(s): The present day challenge is how to obtain germ cells from stem cells to treat patients with cancer and infertility. Much more efforts have been made to develop a procedure for attaining germ cells in vitro. Recently, human umbilical cord-derived mesenchymal stem cells (HUMSCs) have been introduced with higher efficacy for differentiation. In this work, we tried to explore the efficacy of HUMSCs and some effective products of placental cells such as transforming growth factors. This study is aimed to optimize a co-culture condition for HUMSCs with placental cells to obtain primordial germ cells (PGCs) and reach into oocyte-like cells in vitro. Materials and Methods: In this experimental study, HUMSCs and placental cells were co-cultured for 14 days without any external inducer in vitro. Then HUMSCs were assessed for expression of PGC markers; Octamer-binding transcription factor 4(OCT4), Tyrosine-protein kinase Kit (CKIT), Stage specific embryonic antigen 4 (SSEA4), DEAD (Asp-Glu-Ala-Asp) box polypeptide 4(DDX4) and oocyte specific markers; Growth differentiation factor-9(GDF9), Zona pellucida glycoprotein 3(ZP3). The pertinent markers were assessed by immunocytochemistry and Q-PCR. Results: Co-cultured HUMSCs with placental cells (including amniotic and chorionic cells) presented Oct4 and DDX4, primordial germ cells specific markers significantly, but increment in expression of oocyte-like cell specific markers, GDF9 and ZP3 did not reach to statistically significant threshold. Conclusion: Placental cell supplements Transforming growth factor (TGF α, β) and basic fibroblast growth factor (bFGF) in a co-culture model can provide proper environment for induction of HUMSCs into PGCs and expression of oocyte-like markers. � 2015, Mashhad University of Medical Sciences. All rights reserved

Benchmark problem definition and cross-validation for characteristic mode solvers

In October 2016, the Special Interest Group on Theory of Characteristic Modes (TCM) initiated a coordinated effort to perform benchmarking work for characteristic mode (CM) analysis. The primary purpose is to help improve the reliability and capability of existing CM solvers and to provide the means for validating future tools. Significant progress has already been made in this joint activity. In particular, this paper describes several benchmark problems that were defined and analyzes some results from the cross-validations of different CM solvers using these problems. The results show that despite differences in the implementation details, good agreement is observed in the calculated eigenvalues and eigencurrents across the solvers. Finally, it is concluded that future work should focus on understanding the impact of common parameters and output settings to further reduce variability in the results

A Possible Connection Between Plant Longevity and the Absence of Protein Fibrillation: Basis for Identifying Aggregation Inhibitors in Plants

The ability of proteins to aggregate to form well-organized β-sheet rich amyloid fibrils is increasingly viewed as a general if regrettable property of the polypeptide chain. Aggregation leads to diseases such as amyloidosis and neurodegeneration in humans and various mammalian species but is also found in a functional variety in both animals and microbes. However, there are to our knowledge no reports of amyloid formation in plants. Plants are also the source of a large number of aggregation-inhibiting compounds. We reasoned that the two phenomena could be connected and that one of (many) preconditions for plant longevity is the ability to suppress unwanted protein aggregation. In support of this, we show that while protein extracts from the sugar maple tree Acer saccharum fibrillate readily on their own, this process is efficiently abolished by addition of small molecule extracts from the same plant. Further analysis of 44 plants showed a correlation between plant longevity and ability to inhibit protein aggregation. Extracts from the best performing plant, the sugar maple, were subjected to chromatographic fractionation, leading to the identification of a large number of compounds, many of which were shown to inhibit aggregation in vitro. One cautious interpretation is that it may have been advantageous for plants to maintain an efficient collection of aggregation-inhibiting metabolites as long as they do not impair metabolite function. From a practical perspective, our results indicate that long-lived plants may be particularly appropriate sources of new anti-aggregation compounds with therapeutic potential

Using intervention mapping to develop a home-based parental-supervised toothbrushing intervention for young children

BACKGROUND: Dental caries in young children is a major public health problem impacting on the child and their family in terms of pain, infection and substantial financial burden on healthcare funders. In the UK, national guidance on the prevention of dental caries advises parents to supervise their child's brushing with fluoride toothpaste until age 7. However, there is a dearth of evidence-based interventions to encourage this practice in parents. The current study used intervention mapping (IM) to develop a home-based parental-supervised toothbrushing intervention to reduce dental caries in young children. METHODS: The intervention was developed using the six key stages of the IM protocol: (1) needs assessment, including a systematic review, qualitative interviews, and meetings with a multi-disciplinary intervention development group; (2) identification of outcomes and change objectives following identification of the barriers to parental-supervised toothbrushing (PSB), mapped alongside psychological determinants outlined in the Theoretical Domains Framework (TDF); (3) selection of methods and practical strategies; (4) production of a programme plan; (5) adoption and implementation and (6) Evaluation. RESULTS: The comprehensive needs assessment highlighted key barriers to PSB, such as knowledge, skills, self-efficacy, routine setting and behaviour regulation and underlined the importance of individual, social and structural influences. Parenting skills (routine setting and the ability to manage the behaviour of a reluctant child) were emphasised as critical to the success of PSB. The multi-disciplinary intervention development group highlighted the need for both universal and targeted programmes, which could be implemented within current provision. Two intervention pathways were developed: a lower cost universal pathway utilising an existing national programme and an intensive targeted programme delivered via existing parenting programmes. A training manual was created to accompany each intervention to ensure knowledge and standardise implementation procedures. CONCLUSIONS: PSB is a complex behaviour and requires intervention across individual, social and structural levels. IM, although a time-consuming process, allowed us to capture this complexity and allowed us to develop two community-based intervention pathways covering both universal and targeted approaches, which can be integrated into current provision. Further research is needed to evaluate the acceptability and sustainability of these interventions

Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity

Aggregation of α-synuclein (αSN) is implicated in neuronal degeneration in Parkinson's disease and has prompted searches for natural compounds inhibiting αSN aggregation and reducing its tendency to form toxic oligomers. Oil from the olive tree (Olea europaea L.) represents the main source of fat in the Mediterranean diet and contains variable levels of phenolic compounds, many structurally related to the compound oleuropein. Here, using αSN aggregation, fibrillation, size-exclusion chromatography–multiangle light scattering (SEC-MALS)-based assays, and toxicity assays, we systematically screened the fruit extracts of 15 different olive varieties to identify compounds that can inhibit αSN aggregation and oligomer toxicity and also have antioxidant activity. Polyphenol composition differed markedly among varieties. The variety with the most effective antioxidant and aggregation activities, Koroneiki, combined strong inhibition of αSN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic αSN oligomers. Fractionation of the Koroneiki extract identified oleuropein aglycone, hydroxyl oleuropein aglycone, and oleuropein as key compounds responsible for the differences in inhibition across the extracts. These phenolic compounds inhibited αSN amyloidogenesis by directing αSN monomers into small αSN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences in the level of effective phenolic compounds in different olive varieties, insights that have implications for long-term human health

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases