Evaluation of Diuretic Activity of Aqueous and Methanol Extracts of Lepidium sativum Garden Cress (Cruciferae) in Rats

Purpose: The present study was undertaken to investigate diuretic effect of aqueous and methanol extracts of the dried seeds of Lepidium sativum in normal rats.Method: Aqueous and methanol extracts of L. sativum seeds were administered to experimental rats orally at doses of 50 and 100 mg/kg p.o. Hydrochlorothiazide (10 mg/kg) was used as positive control instudy. The diuretic effect of the extracts was evaluated by measuring urine volume, sodium and potassium content, conductivity and pH.Result: Urine volume was significantly increased by the two doses of aqueous and methanol extracts in comparison to control group. While the excretion of sodium was also increased by both extracts, potassium excretion was only increased by the aqueous extract at a dose of 100 mg/kg. There was no significant change in the conductivity and pH of urine after administration of the L. sativum extracts. The diuretic effect of the extracts was comparable to that of the reference standard (hydrochlorothiazide) and the methanol had the additional advantage of a potassium-conserving effect.Conclusion: We can conclude that aqueous and methanol extracts of L. sativum produced notable diuretic effect which appeared to be comparable to that produced by the reference diuretic HCTZ. The present study provides a quantitative basis for explaining the folkloric use of L. sativum as a diuretic agent in Moroccan population

Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency

Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3

Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

<span style="font-size:12.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-ansi-language: EN-GB;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-GB">Potassium phosphate <span style="mso-bidi-font-weight:bold">catalyzed efficient synthesis of 3-carboxycoumarins</span></span>

1039-1042<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">An efficient and rapid synthesis of 3-carboxycoumarins has been expediently accomplished by a reaction of salicylaldehyde with Meldrum’s acid using potassium phosphate as an inexpensive catalyst at ambient temperature. </span

Estrogen treatment decreases the osteoclast precursor population and TNF receptor expression by these cells in vivo in postmenopausal women

Previous animal and in vitro studies have established the CD14+ monocyte as the cellular precursor which differentiates into mature osteoclasts. Monocytes express key surface receptors, including c-Fms (the receptor for M-CSF), RANK (the receptor for RANKL), and TNFR1 and TNFR2 (the receptors for TNFα), which are involved in the differentiation of these cells into osteoclasts, at which point the cells also express the calcitonin receptor (CTR). Furthermore, the recently discovered OSCAR and TREM2 receptors provide important co-stimulatory functions for osteoclast development. However, the impact of estrogen (E) on monocyte differentiation and function into osteoclast precursors in vivo in humans has not yet been determined. Thus, we examined effects of E on the expression of these surface receptors on bone marrow mononuclear cells (MNCs) following 4 weeks of E treatment (100 üg/d estradiol patches; n = 17) vs. untreated (control; n = 17) postmenopausal women. The Mean Fluorescence Intensity (MFI, a surrogate for the concentration/cell of the protein) for each receptor as well as the percentage of cells (as a fraction of bone marrow MNCs) expressing the various receptors was assessed using flow cytometry. As shown in the Table, E treatment resulted in a significant decrease in the MFI for TNFR2 on bone marrow MNCs. Moreover, the percentage of bone marrow MNCs co-expressing RANK/CD14, TNFR2/CTR, or CTR was also significantly reduced by E. By contrast, E had no effect on expression of c-Fms, OSCAR, or TREM2. Table.These studies thus represent the first systematic examination of the effects of E on osteoclast precursor populations in vivo in humans. Collectively, they indicate that E decreases the differentiation of monocytes towards mature osteoclasts and suggests this is mediated principally through regulation of the TNF receptor family rather then through modulating co-stimulatory receptor expression