Comparative Analysis of Estragole, Methyleugenol, Myristicin, and Elemicin Regarding Micronucleus Formation in V79 Cells.

Alkenylbenzenes occur as natural constituents in a variety of edible plants, in particular those herbs and spices used to give a distinctive flavor to a range of food and feed items. Some alkenylbenzenes with relevance for food, such as estragole and methyleugenol, are known to be genotoxic and carcinogenic in rodents. However, the genotoxic and carcinogenic potential of other structurally related alkenylbenzenes, such as myristicin and elemicin, is still under scientific discussion.

Occurrence of Alkenylbenzenes in Plants: Flavours and Possibly Toxic Plant Metabolites.

Alkenylbenzenes are naturally occurring secondary plant metabolites. While some of them are proven genotoxic carcinogens, other derivatives need further evaluation to clarify their toxicological properties. Furthermore, data on the occurrence of various alkenylbenzenes in plants, and especially in food products, are still limited.

Natural Compounds in Plant-Based Food.

Plant-based foods include a wide range of products, such as fruits, vegetables, herbs and spices, as well as food products based on them, such as sauces, soups, or beverages [...

3-MCPD as contaminant in processed foods: State of knowledge and remaining challenges.

3-Chloro-1,2-propanediol (3-MCPD) and its fatty acid esters (FE) are present as contaminants in different processed foods. Based on the available toxicological data the potential risk of 3-MCPD and its FE to human health was assessed by risk assessment authorities, including the European Food Safety Authority (EFSA). Considering the available data, EFSA concluded that 3-MCPD is a non-genotoxic compound exhibiting secondary carcinogenic effects in rodents.

Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food.

Alkenylbenzenes represent a group of naturally occurring substances that are synthesized as secondary metabolites in various plants, including nutmeg and basil. Many of the alkenylbenzene-containing plants are common spice plants and preparations thereof are used for flavoring purposes. However, many alkenylbenzenes are known toxicants.

MiRNA-29b and miRNA-497 Modulate the Expression of Carboxypeptidase X Member 2, a Candidate Gene Associated with Left Ventricular Hypertrophy.

Left ventricular hypertrophy (LVH) is a major risk factor for adverse cardiovascular events. Recently, a novel candidate gene encoding the carboxypeptidase X member 2 (CPXM2) was found to be associated with hypertension-induced LVH. CPXM2 belongs to the M14 family of metallocarboxypeptidases, yet it lacks detectable enzyme activity, and its function remains unknown.

Autoantibodies Targeting AT- and ET-Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor.

Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (ATR) and endothelin-1 type A receptors (ETR) on downstream signaling events and endothelial cell proliferation.

Cpxm2 as a novel candidate for cardiac hypertrophy and failure in hypertension.

Treatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as a genetic locus affecting LV mass.

Alkenylbenzenes in Foods: Aspects Impeding the Evaluation of Adverse Health Effects.

Alkenylbenzenes are naturally occurring secondary plant metabolites, primarily present in different herbs and spices, such as basil or fennel seeds. Thus, alkenylbenzenes, such as safrole, methyleugenol, and estragole, can be found in different foods, whenever these herbs and spices (or extracts thereof) are used for food production. In particular, essential oils or other food products derived from the aforementioned herbs and spices, such as basil-containing pesto or plant food supplements, are often characterized by a high content of alkenylbenzenes.

TMEM63C, a Potential Novel Target for Albuminuria Development, Is Regulated by MicroRNA-564 and Transforming Growth Factor beta in Human Renal Cells.

Introduction: Transmembrane protein (TMEM) 63C is a member of the TMEM gene family and was recently linked to glomerular filtration barrier function and albuminuria. Its molecular function and expression regulation are largely unknown.

Objective: In this study, we set out to characterize the regulating impact of microRNAs (miRNAs) such as miRNA-564 (miR-564) on TMEM63C expression in renal cells.

Tmem63c is a potential pro-survival factor in angiotensin II-treated human podocytes.

Aims: Human podocytes (hPC) play an important role in the pathogenesis of renal diseases. In this context, angiotensin II (Ang II) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) play a crucial role in podocyte injury. Recently, transmembrane protein (Tmem) 63c, a member of the Tmem-family was found to be expressed in kidney and associated with podocyte function.

Heating of food containing sucralose might result in the generation of potentially toxic chlorinated compounds.

Sucralose is widely used as non-caloric intense artificial sweetener. It was previously considered to be thermally stable and safe. This was based on studies performed in the early 1990s.

What do we know about health risks related to thebaine in food?

Opium alkaloids such as morphine and thebaine occur in the latex of Papaver somniferum varieties. Some varieties are used for both, pharmaceutical opium alkaloid generation and poppy seed production for food use. Poppy seeds can be contaminated with opium alkaloid-containing latex, e.

Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links to kidney damage.

Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging. Here, we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models. We characterized its genomic architecture by congenic substitution mapping, targeted next-generation sequencing, and compartment-specific RNA sequencing analysis in isolated glomeruli.

The impact of α-Lipoic acid on cell viability and expression of nephrin and ZNF580 in normal human podocytes.

Human podocytes (hPC) are essential for maintaining normal kidney function and dysfunction or loss of hPC play a pivotal role in the manifestation and progression of chronic kidney diseases including diabetic nephropathy. Previously, α-Lipoic acid (α-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of α-LA on hPC under non-diabetic conditions is unknown.

Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy.

Background: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy.

Metformin modulates apoptosis and cell signaling of human podocytes under high glucose conditions.

Diabetic nephropathy, which is associated with loss of human (h) podocytes (PC), is a major complication in diabetes mellitus. High-glucose modulates AMP-activated protein kinase (AMPK) signaling and cell apoptosis. Metformin has been demonstrated to reduce apoptosis and albuminuria in type 2 diabetes.

Tissue Factor: A Conventional or Alternative Target in Cancer Therapy.

Background: Tissue factor (TF) is an evolutionary conserved glycoprotein that plays an important role in the pathogenesis of cancer. TF is expressed in 2 naturally occurring protein isoforms, membrane-bound full-length (fl)TF and soluble alternatively spliced (as)TF. Both isoforms have been shown to affect a variety of pathophysiologically relevant functions, such as tumor-associated angiogenesis, thrombogenicity, tumor growth, and metastasis.

Regulation of podoplanin expression by microRNA-29b associates with its antiapoptotic effect in angiotensin II-induced injury of human podocytes.

Background: Angiotensin (Ang)II is involved in induction of proteinuria, renal injury, and apoptosis and thus a major contributor to the development of chronic kidney disease. Podocytes are of major importance for the pathogenesis of several kidney diseases. Decrease of podoplanin (PDPN) in podocytes and podocyte loss has been associated with the development of proteinuria.

The role of tissue factor isoforms in cancer biology.

Tissue Factor (TF) is an evolutionary conserved glycoprotein, which is of immense importance for a variety of biologic processes. TF is expressed in two naturally occurring protein isoforms, membrane-bound "full-length" (fl)TF and soluble alternatively spliced (as)TF. The TF isoform expression is differentially modulated on post-transcriptional level via regulatory factors, such as serine/arginine-rich (SR) proteins, SR protein kinases and micro (mi)RNAs.

Regulation of vascular function on posttranscriptional level.

Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (patho)physiologic conditions. Alternative splicing as well as micro (mi)RNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF) or the endothelial nitric oxide synthase (eNOS).

The impact of microRNAs on the regulation of tissue factor biology.

Tissue factor (TF) and its isoforms play an important role in a variety of physiologic and pathophysiologic functions, such as initiation of blood coagulation, vessel wall hemostasis, angiogenesis, and tumorigenesis. Micro(mi)RNAs are crucial for post-transcriptional control of protein generation by regulating the expression of one-third of all human genes. In recent years, miRNAs were shown to modulate the expression and biologic function of TF in different physiologic- and pathophysiologic-relevant settings, such as in autoimmune diseases and in different types of cancer.

Regulation of pro-angiogenic tissue factor expression in hypoxia-induced human lung cancer cells.

Alternative splicing is a key regulatory mechanism for cellular metabolism controlling cell proliferation and angiogenesis, both of which are crucial processes for tumorigenesis under hypoxia. Human cells express two tissue factor (TF) isoforms, alternatively spliced TF (asTF) and 'full length' TF (flTF). flTF is the major source of thrombogenicity whereas, the function of soluble asTF, particularly in cancer, is widely unknown.

CCN1: a novel inflammation-regulated biphasic immune cell migration modulator.

In this study, we performed a comprehensive analysis of the effect of CCN1 on the migration of human immune cells. The molecule CCN1, produced by fibroblasts and endothelial cells, is considered as an important matrix protein promoting tissue repair and immune cell adhesion by binding various integrins. We recently reported that CCN1 therapy is able to suppress acute inflammation in vivo.

Bivalirudin inhibits periprocedural platelet function and tissue factor expression of human smooth muscle cells.

Aim: A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration.