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Methods of Discovering New Bile Acids and Use in Treating Inflammatory Diseases

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition. However, we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host sphingolipids and bile acids. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. The synthesis of bile acids takes place in the liver and recent research has shown that bile acids can act as signaling molecules and activate a number of molecules. A primary focus has been on the Farnesoid X receptor (FXR) which plays an important role in bile acid synthesis and in regulation of glucose, lipid and energy metabolism.

Prediction Tools for Vedolizumab Drug Exposure and Efficacy for Ulcerative Colitis and Crohn’s disease

Vedolizumab (VDZ) is an effective therapy for the management of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) who have failed conventional therapy with aminosalicylates, corticosteroids, and thiopurines, as well as biologic therapy with tumor necrosis factor (TNF) antagonists. Several studies have identified potential predictors of treatment outcomes; however, the optimal approach to integrating predictors into routine practice is uncertain.No prior decision support tools exist to predict VDZ drug exposure in UC and CD and link this back to differences in effectiveness or response to VDZ dose escalation. By having a tool that can predict at baseline prior to start of therapy whether VDZ will be effective and what a patients drug exposure profile will be with VDZ, the provider can 1) determine if VDZ is an appropriate therapy to begin, 2) proactively monitor those patients deemed high risk for treatment failure with VDZ, and 3) proactively measure drug concentrations for VDZ to then increase the dose or the interval at which VDZ is administered to improve outcomes.

Epigenetic Profile-Based Biomarkers for Irritable Bowel Syndrome

UCLA researchers from the Vatche and Tamar Manoukian Division of Digestive Diseases have discovered an innovative approach to diagnose irritable bowel syndrome. This method uses a set of epigenetic profiles as biomarkers and is highly sensitive compared to conventional diagnostic methodologies.

Flexible Stretchable Electrode And Recording Method For Gastrointestinal Prostheses

UCLA researchers in the Department of Bioengineering and Surgery have developed an electrode for stimulation and recording of intestinal peristalsis that uses a novel impedance-based sensing method.

Novel Network-Resetting Therapeutics for Inflammatory Bowel Disease and Associated Chronic Diseases

The gut barrier is comprised of a single layer of epithelial cells that serve as a physical barrier against multiple stressors, e.g., microbes, microbial products, and antigens. Although it is widely accepted that an impaired gut barrier contributes to the initiation and progression of inflammatory bowel disease (IBD), to date there is no biomarker or therapeutic target to detect/heal the barrier. IBD is of multifactorial origin -- luminal dysbiosis, immune deregulation, genetics, and environmental factors all contribute to its development and progression. Currently, IBD patients are offered expensive inflammation-reducing therapies have only a ~30-50% response-rate; 40% of responders become refractory to treatment within a year. Unfortunately, 100% face the risk of morbid side effects. Therefore, there is an urgent need to develop alternative modalities, in this case, ways to strengthen the gut barrier and heal broken junctions.

Novel Small Molecule Drug for the Treatment of Constipation and Oxalate Kidney Stones

UCSF researchers have developed a novel small molecule drug that specifically targets and inhibits SLC26A3 (DRA), an anion exchanger whose inhibition is expected to have therapeutic benefit in constipation and oxalate kidney stone disease.

Potent TMEM16A Small Molecule Treatment for Inflammatory and Reactive Airway Diseases, Asthma, Hypertension, Pain and Cancer

A novel class of 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as potent TMEM16A inhibitors

Functional Manipulation of the Gut Microbiome Using a Personalized Approach

The use of traditional probiotic microorganisms to provide therapeutic function for the gut microbiome has a number of limitations. Probiotic bacteria do not colonize the gut because they can’t compete with the resident flora that have evolved for that environment. Current probiotics are a single strain which when used in multiple hosts have not had great success in broad populations and are therefore unpredictable. To alleviate the above problem, a new approach is necessary to colonize the human gastrointestinal tract with greater reliability and for therapeutic value to the patient. 

Breast Milk as a Source, Incubation/Storage Medium, and Delivery System for Infant Mucosal Immunity Bacteriophage

Researchers at the University of California, Davis have developed a method to harvest and enrich symbiotic bacteriophage to promote bacterial immunity.

Test for Intestinal Permeability

Researchers from the Department of General Surgery at UCLA have developed an easy-to-use method to determine intestinal permeability that utilizes an FDA-approved non-absorbable dye.

A Method For Screening Drugs, Nutritional Supplements And Probiotics For Their Ability To Enhance Or Disrupt The Gut Barrier

The gut is a complex environment; the gut mucosa maintains immune homeostasis under physiological circumstances by serving as a barrier that restricts access of trillions of microbes, diverse microbial products, food antigens and toxins to the largest immune system in the body. The gut barrier is comprised of a single layer of epithelial cells, bound by cell-cell junctions, and a layer of mucin that covers the epithelium. Loosening of the junctions induced either by exogenous or endogenous stressors, compromises the gut barrier and allows microbes and antigens to leak through and encounter the host immune system, thereby generating inflammation and systemic endotoxemia. An impaired gut barrier (e.g. a leaky gut) is a major contributor to the initiation and/or progression of various chronic diseases including, but not limited to, metabolic endotoxemia, type II diabetes, fatty liver disease, obesity, atherosclerosis and inflammatory bowel diseases. Despite the growing acceptance of the importance of the gut barrier in diseases, knowledge of the underlying mechanism(s) that reinforce the barrier when faced with stressors is incomplete, and viable and practical strategies for pharmacologic modulation of the gut barrier remain unrealized.

A Novel Method to Generate Specific and Permanent Macromolecular Covalent Inhibitors

UCSF researchers have invented a novel method to generate covalent macromolecular inhibitors. This strategy allows a peptide inhibitor to bind to its target protein specifically and irreversibly through proximity-enabled bioreactivity.

Simple and Rapid Method for the Quantification of Haloginated Dissaccharides (i.e. Sucralose) in an Aqueous Media

Sucralose is widely used as an artificial sweetener because of its low caloric content and is sweeter than table sugar (sucrose). Due to its resistance to metabolic degradation, sucralose can also be used as a marker for noninvasively evaluating the gastrointestinal small digestive tract (intestine) or colonic permeability. This urinary marker is traditionally analyzed by time consuming and expensive methods, such as high performance liquid chromatography coupled to mass spectrometry (HPLC-MS) or evaporative light scatter as the detectors. UCSC researchers have developed an alternative method using a chemical-fluorescent technique for rapid analysis of halogenated disaccharides, such as sucralose.

Novel Methods to Prevent and Treat Liver and Colon Cancer

Researchers at the University of California, Davis have developed a method to treat liver and colon cancer using natural or synthetic retinoids in combination with histone deacetylase inhibitors.

UCLA Inventors Identify Specific Molecular Diagnostic Markers For Ulcerative Colitis

UCLA researchers in the Division of Digestive Disease in the Department of Medicine at the David Geffen School of Medicine, led by Drs. Charalabos Pothoulakis and Dimitrios Iliopoulos, have identified several biomolecules that are potential diagnostic markers for ulcerative colitis. These markers can be used singularly or combined, depending on the diagnostic testing need. There is increased flexibility for testing as a positive correlation is related to increased marker levels or the presence of the molecule, depending on the biomarker. Researchers have also identified a marker that can distinguish ulcerative colitis from Crohn’s Disease.

New Indication for Use of Niacin (Nicotinic Acid) for Treatment, Prevention and Reversal of Fatty Liver Disease

Non alcoholic fatty liver disease (NAFLD) is a health problem that affects approximately 30% of the population, and the up to 75% of people afflicted with obesity and type 2 diabetes. Currently, no therapeutic agent for the prevention or treatment of fatty liver disease exists. Researchers at UC Irvine have developed a strategy that suggests treatment for fatty liver disease and/or NAFLD using niacin and/or its metabolites.

Gluten Digesting Bacterial Strains

Over the last few years Celiac disease and gluten intolerance has been on the rise. Currently, the only treatment is a gluten free diet, which is very difficult to follow. Cross contamination of gluten free products is common and many food items that seemingly contain no wheat contain gluten-derived products. Here we describe several bacterial strains isolated from humans for their gluten degrading activities. These bacteria may be used to eliminate trace amounts of wheat contaminants from gluten free products or as probiotic therapy.

Novel ELISA assay to detect SULF2 in patient samples

This ELISA technique detects Sulfatase2 (SULF2), an extracellular heparan sulfate-degrading enzyme that is overexpressed in many cancers. Furthermore, this technique can potentially serve as a diagnostic for cirrhosis.

Mouse Model for Human Non-Alcoholic Steatohepatitis and Steatolic Hepatocellular Carcinoma

Currently, there are no good mouse models to study the development of non-alcoholic steatohepatitis (NASH) and its progression to steatolic hepatocellular carcinoma (HCC) in less than one year. While there are other models of NASH in mice, none of the currently available models closely mimics the human disease and most are models of toxic liver damage associated with weight loss rather than obesity. 

Method to Expand and Transduce Cultured Human Small and Large Intestinal Stem Cells

Dr. Martin G. Martin and colleagues in the Department of Pediatric Gastroenterology and Surgery at UCLA have developed a novel method of expanding and differentiating human small intestinal stem cells in culture.

Methods of Quantitation and Display of Impedance Data for Estimating Gastroenterology Tract Parameters

Current methodology typically measures both pressure and impedance usingsensors spread over the entire length of the esophagus. Impedance is used to provide a quantitative temporal measure of the advance of bolus in the esophagus, but it does not provide a quantitative measure of the extent of esophageal cross-sectional area or segmental volume.

High Resolution Anoscopy Documentation Diagram

Many institutions are implementing anal cancer screening programs modeled on procedures used in cervical cancer. Analogous to cervical colposcopy screening procedures, the high resolution anoscopy (HRA) poses additional challenges due to unique characteristics of the procedure. This includes the uneven topography and collapsing nature of anal canal, making it a more challenging procedure than cervical colposcopy. Additionally, there is considerable variability in how HRA providers position the patient and document the position of visualized lesions. HRA practitioners about to perform a HRA follow-up examination or ablative treatment typically review prior HRA images saved in free-standing image management software (i.e. image files are generally not linked to electronic medicaI record systems). With these current limitations, there exists a need for a method to standardize how HRA results are documented in the medical record.

A Novel Inflammatory Bowel Disease Marker

Brief description not available

Tungstate Treatment of Inflammatory Bowel Disease-Associated Dysbiosis

Researchers at the University of California, Davis have found that oral treatment of tungstate is an effective treatment of Inflammatory bowel disease.

Identification of Major Cashew and Walnut Allergens

Cashews and walnuts are commonly used in snack foods and as an ingredient in a veriety of processed foods, such as bakery and confectionary products. For those who are allergic to those nuts, consuming them can lead to reactions ranging from dermatitis to deadly anaphylactic shock. Researchers at the University of California, Davis in conjunction with Florida State University have identified specific amino acid sequences in walnut and cashew proteins that produce allergic reactions in humans.

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