Band 6, Heft 3

Genetic and environmental factors, especially nutrition and lifestyle, have been discussed in the literature for their relevance to epidemic obesity. Gene-environment interactions may need to be understood for an improved understanding of the causes of obesity, and epigenetic mechanisms are of special importance. Consequences of epigenetic mechanisms seem to be particularly important during certain periods of life: prenatal, postnatal and intergenerational, transgenerational inheritance are discussed with relevance to obesity. This review focuses on nutrients, diet and habits influencing intergenerational, transgenerational, prenatal and postnatal epigenetics; on evidence of epigenetic modifiers in adulthood; and on animal models for the study of obesity.

The liver X receptors (LXR) are crucial regulators of metabolism. After ligand binding, they regulate gene transcription and thereby mediate changes in metabolic pathways. Modulation of LXR and their downstream targets has appeared to be a promising treatment for metabolic diseases especially atherosclerosis and cholesterol metabolism. However, the complexity of LXR action in various metabolic tissues and the liver side effect of LXR activation have slowed down the interest for LXR drugs. In this review, we summarized the role of LXR in the main metabolically active tissues with a special focus on obesity and associated diseases in mammals. We will also discuss the dual interplay between the two LXR isoforms suggesting that they may collaborate to establish a fine and efficient system for the maintenance of metabolism homeostasis.

Ion channels are integral membrane proteins that undergo important conformational changes as they open and close to control transmembrane flux of different ions. The molecular underpinnings of these dynamic conformational rearrangements are difficult to ascertain using current structural methods. Several functional approaches have been used to understand two- and three-dimensional dynamic structures of ion channels, based on the reactivity of the cysteine side-chain. Two-dimensional structural rearrangements, such as changes in the accessibility of different parts of the channel protein to the bulk solution on either side of the membrane, are used to define movements within the permeation pathway, such as those that open and close ion channel gates. Three-dimensional rearrangements – in which two different parts of the channel protein change their proximity during conformational changes – are probed by cross-linking or bridging together two cysteine side-chains. Particularly useful in this regard are so-called metal bridges formed when two or more cysteine side-chains form a high-affinity binding site for metal ions such as Cd 2+ or Zn 2+ . This review describes the use of these different techniques for the study of ion channel dynamic structure and function, including a comprehensive review of the different kinds of conformational rearrangements that have been studied in different channel types via the identification of intra-molecular metal bridges. Factors that influence the affinities and conformational sensitivities of these metal bridges, as well as the kinds of structural inferences that can be drawn from these studies, are also discussed.

Recently, there have been tremendous advances in the development of various nanotechnology-based platforms for diagnosis and therapy. These nanoplatforms, which include liposomes, micelles, polymers, and dendrimers, comprise highly integrated nanoparticles that provide multiple functions, such as targeting, imaging, and therapy. This review focuses on dendrimer-based nanocarriers that have recently been developed for ‘theranostics (or theragnosis)’, a combination of therapy and diagnostics. We discuss the in vitro and in vivo applications of these nanocarriers in strategies against diseases including cancer. We also explore the use of dendrimers as imaging agents for fluorescence imaging, magnetic resonance imaging, X-ray computed tomography, and nuclear medical imaging.

Testicular germ cell cancer manifests mainly in young adults as a seminoma or non-seminoma. The solid tumors are preceded by the presence of a non-invasive precursor cell, the carcinoma in situ cell (CIS), which shows great similarity to fetal germ cells. It is therefore hypothesized that the CIS cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men.

Sarcoidosis is a multiorgan disease with no single etiology. Evidence over the years points to complex interactions between environmental and genetic factors and a hypersensitive immune response to these insults. This brief overview discusses the uncertainty in the diagnosis of sarcoidosis versus other granulomatous diseases masquerading as sarcoidosis. The diagnostic dilemma is highlighted by a brief case review. The development of newer techniques in molecular biology and the identification of a panel of biomarkers in the future with appreciable specificity and sensitivity would help in the process. Future studies to determine receiver operating curves (ROC) using multiple biomarker combinations would help develop robust testing. More in-depth studies are also needed for defining the immunological basis of sarcoidosis because recent studies implicate Th17 cells in addition to the Th1 cell pathway. It is very likely that direct exposure to environmental agents and systemic distribution of these agents can elicit an exaggerated immune response leading to multiorgan granuloma formation mimicking sarcoidosis. A genetically susceptible host may be necessary to complete the granulomatous response to the particulate matter.