Kendal Jensen

General mechanisms of nicotine-induced fibrogenesis

Cigarette smoking contributes to the development of cancer, and pathogenesis of other diseases. Many chemicals have been identified in cigarettes that have potent biological properties. Nicotine is especially known for its role in addiction and plays a role in other physiological effects of smoking and tobacco use. Recent studies have provided compelling evidence that, in addition to promoting cancer, nicotine also plays a pathogenic role in systems, such as the lung, kidney, heart, and liver. In many organ systems, nicotine modulates fibrosis by altering the functions of fibroblasts. Understanding the processes modulated by nicotine holds therapeutic potential and may guide future clinical and research decisions. This review discusses the role of nicotine in the general fibrogenic process that governs fibrosis and fibrosis‐related diseases, focusing on the cellular mechanisms that have implications in multiple organ systems. Potential research directions for the management of nicotine‐induced fibrosis, and potential clinical considerations with regard to nicotine‐replacement therapy (NRT) are presented.—Jensen, K., Nizamutdinov, D., Guerrier, M., Afroze, S., Dostal, D., Glaser, S. General mechanisms of nicotine‐induced fibrogenesis. FASEB J. 26, 4778–4787 (2012). www.fasebj.org

Hepatic nervous system and neurobiology of the liver.

The liver has a nervous system containing both afferent and efferent neurons that are involved in a number of processes. The afferent arm includes the sensation of lipids, glucose, and metabolites (after eating and drinking) and triggers the nervous system to make appropriate physiological changes. The efferent arm is essential for metabolic regulation, modulation of fibrosis and biliary function and the control of a number of other processes. Experimental models have helped us to establish how: (i) the liver is innervated by the autonomic nervous system; and (ii) the cell types that are involved in these processes. Thus, the liver acts as both a sensor and effector that is influenced by neurological signals and ablation. Understanding these processes hold significant implications in disease processes such as diabetes and obesity, which are influenced by appetite and hormonal signals.

Virion disruption by ozone-mediated reactive oxygen species

It is well documented in the scientific literature that ozone-oxygen mixtures inactivate microorganisms including bacteria, fungi and viruses (Hoff, J.C., 1986. Inactivation of microbial agents by chemical disinfectants. EPA 600 S2-86 067. Office of Water, U.S. Environmental Protection Agency, Washington, DC; Khadre, M.A., Yousef, A.E., Kim, J.-G., 2001. Microbiological aspects of ozone applications in food: a review. J. Food Sci. 66, 1242-1252). In the current study, delivery and absorption of precisely known concentrations of ozone (in liquid media) were used to inactivate virus infectivity. An ozone-oxygen delivery system capable of monitoring and recording ozone concentrations in real time was used to inactivate a series of enveloped and non-enveloped viruses including herpes simplex virus type-1 (HHV-1, strain McIntyre), vesicular stomatitis Indiana virus (VSIV), vaccinia virus (VACV, strain Elstree), adenovirus type-2 (HAdV-2), and the PR8 strain of influenza A virus (FLUAVA/PR/8/34/H1N1; FLUAV). The results of the study showed that ozone exposure reduced viral infectivity by lipid peroxidation and subsequent lipid envelope and protein shell damage. These data suggest that a wide range of virus types can be inactivated in an environment of known ozone exposure.

The physiological roles of secretin and its receptor

Secretin is secreted by S cells in the small intestine and affects the function of a number of organ systems. Secretin receptors (SR) are expressed in the basolateral domain of several cell types. In addition to regulating the secretion of a number of epithelia (e.g., in the pancreas and biliary epithelium in the liver), secretin exerts trophic effects in several cell types. In this article, we will provide a comprehensive review on the multiple roles of secretin and SR signaling in the regulation of epithelial functions in various organ systems with particular emphasis in the liver. We will discuss the role of secretin and its receptor in health and biliary disease pathogenesis. Finally, we propose future areas of research for the further evaluation of the secretin/secretin receptor axis in liver pathophysiology.

Therapeutic actions of melatonin on gastrointestinal cancer development and progression.

Melatonin exerts a multitude of physiological functions including the regulation of the sleep cycle and circadian rhythm. Although the synthesis of melatonin in the pineal gland is regulated by changes in the light/dark cycle, the release of melatonin in the gastrointestinal tract is related to food consumption. Melatonin regulates antioxidative processes and it improves T-helper cell response by stimulating the production of specific cytokines. Melatonin is directly involved in preventing tumor initiation, promotion, and progression in a variety of cancers of the gastrointestinal tract including colorectal cancer, cholangiocarcinoma, hepatocarcinoma, and pancreatic carcinoma. This paper is a review of the literature regarding melatonin in the gastrointestinal tract and as a potential therapy for gastrointestinal cancers.

Autocrine regulation of biliary pathology by activated cholangiocytes

The bile duct system of the liver is lined by epithelial cells (i.e., cholangiocytes) that respond to a large number of neuroendocrine factors through alterations in their proliferative activities and the subsequent modification of the microenvironment. As such, activation of biliary proliferation compensates for the loss of cholangiocytes due to apoptosis and slows the progression of toxic injury and cholestasis. Over the course of the last three decades, much progress has been made in identifying the factors that trigger the biliary epithelium to remodel and grow. Because a large number of autocrine factors have recently been identified as relevant clinical targets, a compiled review of their contributions and function in cholestatic liver diseases would be beneficial. In this context, it is important to define the specific processes triggered by autocrine factors that promote cholangiocytes to proliferate, activate neighboring cells, and ultimately lead to extracellular matrix deposition. In this review, we discuss the role of each of the known autocrine factors with particular emphasis on proliferation and fibrogenesis. Because many of these molecules interact with one another throughout the progression of liver fibrosis, a model speculating their involvement in the progression of cholestatic liver disease is also presented.

Liver Regeneration: The Stem Cell Approach

The liver is well-known for its ability to regenerate in response to damage. While little is known about the precise molecular mechanism governing liver regeneration, much research has explored the signals and stem cells that hold the potential for liver regeneration. Research has uncovered stem cells isolated in various organs capable of becoming hepatic or hepatic-like cells. Furthermore, in some systems, the signals involved in their transformation have been described. This chapter will review the current knowledge and involvement of stem cells, both hepatic and extrahepatic, in the process of liver regeneration. The therapeutic potential of modulating the natural liver to regenerate during disease, and transplantation of extrahepatic cells will be discussed.