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Gut Microbiome Enhancement via Co-delivery of Antibodies and Activated Bacterial Strains

Researchers at the University of California, Davis have developed a mechanism to deliver unique complexes of protective antibodies and probiotics to the gut.

Therapeutic Approach for Inflammatory Bowel Disease by Targeting Microbial Proteases

Ulcerative colitis (UC), an inflammatory bowel disease (IBD), is characterized by chronic inflammation of the colon, with severity of mucosal inflammation being associated with a higher risk of work disability, hospitalization, colorectal cancer, and colectomy. Non-specific immunosuppressive agents targeting the host, such as steroids, thiopurines, and/or biologics, are used to offset the natural history of disease in patients with moderate-severe inflammation. These therapies are, however, associated with significant risks and often ineffective in adequately managing disease. Genomic technologies have identified associations between microbial dysbiosis, or temporal shifts in composition, and UC severity. While recent efforts extended profiling of microbiota in UC beyond genomics, it remains poorly understood if these shifts are causal or associative in nature, and which mechanisms govern pathogenic roles of the microbiome in UC.

Selective Antimicrobial Peptides From Human Milk For Treatment Of Severe Infections

Researchers at the University of California, Davis have developed human milk-derived peptides that have demonstrated broad-spectrum, antibacterial, activity against a variety of harmful pathogens - without these peptides harming most, non-pathogenic, bacterial, flora.

New Non-Invasive Markers To Assess Efficacy Of Anti-Integrin Therapies

Inflammatory bowel disease is a chronic disease, which affects the lower bowel parts or the entire GI tract, causing symptoms like abdominal pain, diarrhea, fever and weight loss. An estimated two million people in North America suffer from IBD seemingly caused by an overactive mucosal immune system. Crohn’s Disease and ulcerative colitis (UC) are the major groups of inflammatory conditions that make up IBD and are incurable, serious and chronic organic diseases of the intestinal tract.   Recently, anti-integrin monoclonal antibodies have been approved by the FDA as therapeutic agents for treatment of IBD and there are a number of phase three clinical trials ongoing using monoclonal antibody therapy. The immune system responds to the inflammation that is part of the immunopathology of IBD and acts by recruiting inflammatory cells to the intestinal lesions.  Intergrins, specifically alpha 4-β7, plays a key role in mediating leukocyte trafficking from the circulation to the vascular endothelial barrier in gut-associate lymphoid tissue with the ligand MAdCAM-1. The use of anti-integrin therapy targeting alpha 4-β7 reduces the number of immune cells to the gut endothelium. However, the precise identity of the cell subsets depleted from the intestinal lamina by these anti-integrin drugs have not been identified. Thus, there is an unmet need to further develop tools that allow for the identification of the critical effector cell subsets targeted by these drugs in the intestine.

Human-Centered Drug Discovery: A Methodology To Identify And Validate High-Value Therapeutic Targets For Human Diseases

Modeling diseases as networks has helped simplify an otherwise complex web of multi‐cellular processes; however, an exclusive reliance on symmetric relationships in these networks overlooks the existence of disease continuum states and loses information relevant to pathogenesis and for the development of therapeutics. Network‐based analyses severely influenced by symmetric analyses have helped formalize Network Medicine as a field and deliver many successes, but drugs that can predictably re‐set the network in complex multi‐component diseases are yet to emerge.

Wirelessley Powered Stimulator

UCLA researchers in the Department of Electrical and Computer Engineering have developed a battery-less implantable pulse generator with concise circuitry and mm-scale form factor.

Triazolo/Phenylpyrimidine Compounds as Novel Candidate Treatments for Schistosomiasis

Schistosomiasis is a disease caused by infection with parasitic flatworms called schistosomes. The three major medically important species are Schistosoma mansoni (causing intestinal schistosomiasis in Africa and South America), S. japonicum (intestinal schistosomiasis in East Asia), and S. haematobium (causing genitourinary schistosomiasis in Africa and the Middle East). Signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine.  The treatment of schistosomiasis serves three purposes: reversing acute or early chronic disease, preventing complications associated with chronic infection, and preventing neuroschistosomiasis. The goal of treatment is to remove the worms that produce the eggs which, in turn, are responsible for disease morbidity and mortality. There is no effective vaccine against schistosomiasis.

Using Bacteria for Gut Health Improvement and Weight Management

Researchers at the University of California, Davis have developed a method of using bacteriocin peptides to reduce gut inflammation, improve gut barrier function, and reduce obesity in humans.

Novel Biomarker For GI Diseases

UCLA researchers at the David Geffen School of Medicine have discovered a small antimicrobial peptide elafin to be used as a biomarker for evaluating inflammatory bowel disease activity and the development of intestinal fibrosis.

Prevention Of The Late Complications Of Acute Pancreatitis

UCLA researchers in the Department of Medicine and Surgery have developed a novel therapeutic for the prevention of late inflammatory complications in severe acute pancreatitis patients.

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 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

Liquid Biopsy Diagnostic for Precursor Lesions of Pancreatic Cancer

These highly specific biomarkers distinguish potentially malignant mucinous cysts from benign nonmucinous cysts in the pancreas to help diagnose precursor lesions of pancreatic ductal adenocarcinoma. The biomarkers can be detected through enzymatic assays with exceptional accuracy and sensitivity.

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.

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