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Chronic inflammation is clearly associated with an increase in the risk of cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) are well documented as agents that inhibit tumor growth and with long-term use can prevent tumor development. NSAID-activated gene (NAG-1), a unique member of the TGF-beta superfamily, is highly induced by NSAIDs and numerous drugs and chemicals with anti-tumorigenic activities.

Airway diseases, such as Asthma and Chronic Obstructive Pulmonary Disease (COPD), constitute a major health burden worldwide. It is estimated, for example, that nearly 15.0% of the adult population in the US are affected with such diseases, and the economic cost burden is over $23 billion annually. Unfortunately, the current options for treatment of such diseases are quite limited, consisting only of bronchodilators and inhaled steroids. The need for a novel and more effective class of therapeutics agents is imperative.

This invention concerns "knockout" animals, including mice, which have a deficit of functional steroid hormone receptors, DNA constructs containing the mutations, and methods for producing the animals. The mutation is introduced into the animal or its ancestors at an embryonic stage. These knockout animals provide a model system for studying the biological role of hormones, including steroid hormones and sex steroids, in growth, development, morphological differentiation, and sexual and reproductive behavior and cycles, etc.

Biological radicals resulted from oxidative stress has been implicated in human diseases, such as cancer and aging. There is, however, a paucity of reliable methods for in vivo or ex vivo detection of either radical formation, the end-products of radical formation or susceptibility for radical formation. The chicken polyclonal anti-DMPO can be used to detect the stable nitrone end-product of protein and DNA radicals in ELISA assays, blot analyses and confocal microscopy.

Biological radicals resulted from oxidative stress has been implicated in human diseases, such as cancer and aging. There is, however, a paucity of reliable methods for in vivo or ex vivo detection of either radical formation, the end-products of radical formation or susceptibility for radical formation. The Rabbit polyclonal anti-DMPO can be used to detect the stable nitrone end-product of protein and DNA radicals in ELISA assays, blot analyses and confocal microscopy.

The estrogen-related receptor alpha (ERRalpha) and proliferator-activated-receptor-gamma coactivator-1alpha (PGC-1alpha) play major roles in transcriptional control of cellular energy metabolism. In particular ERRs are required for the response to various environmental challenges that require high energy levels by the organism. As central regulators of energy homeostasis, ERRs may also implicate in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome.

Leucine rich repeats and calponin homology containing protein 4 (Lrch4) is a gene that encodes a protein predicted to have a C-terminal transmembrane domain, a calponin homology domain, and 5-8 leucine rich repeats (LRRs). We silenced Lrch4 in RAW 264.7 macrophages as well as CD14-MD2-TLR4-HEK293 cells and found that Lrch4 knockdown attenuates responsiveness of cells to LPS and other pathogen-associated molecules. These findings suggest that Lrch4 is a regulator of the innate immune response.

CAR (nuclear constitutive active receptor) is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. It is primarily responsible for sensing foreign toxic substances and in response up regulating the expression of proteins involved in the detoxification and clearance of these substances from the body. CAR is constitutively active in the absence of a ligand but is regulated by both agonists and inverse agonists.

Tristetraprolin (TTP) is the prototype member of a small family of RNA binding proteins that bind to specific types of AU-rich elements in the 3'UTRs of target mRNAs and promote their rapid turnover. One of the targets destabilized by TTP is Tumor necrosis factor alpha (TNF). TNF has long been a target of anti-inflammatory drug development, in which recombinant protein molecules based on TNF antibodies or TNF receptors have been used to bind directly to TNF and inactivate it.

Electron Spin Resonance (ESR) is an universal, specific tool for the detection of free radicals in biological systems. Its application to the investigation of free radicals from whole animals, organs, and cells has been made possible by the spin-trapping technique. In a Spin-trapping experiment, a spin trap such as DMPO (5,5-dimetryl-1-pyrroline N-oxide) reacts specifically with one or more types of free radical to form radical-derived nitrone adducts that are much more stable than the original free radicals.