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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.

Quantitative Determination Of Esterified Eicosanoids and Related Oxygenated Metabolites After Alkaline Hydrolysis

Eicosanoids and related metabolites, sometimes referred to as oxylipins, are a group of structurally diverse metabolites that derive from the oxidation of PUFAs, including arachidonic acid, linoleic acid, and linolenic acid, dihomo linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. They are locally acting bioactive signaling lipids that regulate a diverse set of homeostatic and inflammatory processes. Given the important regulatory functions in numerous physiological and pathophysiological states, the accurate measurement of eicosanoids and other oxylipins is of great clinical interest and lipidomics is now widely used to screen effectively for potential disease biomarkers.

Circulating Lipidomic Signature To Identify Nonalcoholic Fatty Liver Disease

Fatty liver disease (or steatohepatis) is often associated with excessive alcohol intake or obesity, but also has other causes such as metabolic deficiencies including insulin resistance and diabetes. The causation of a fatty liver results from triglyceride fat accumulation in vacuoles of the liver cells resulting in decreased liver function, and possibly leading to cirrhosis or hepatic cancer. Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease occurring in the absence of alcohol abuse. There is a clinical need for a simple test to identify individuals with nonalcoholic fatty liver disease (NAFLD) in the population. While circulating lipids have been used for this purpose, the large number of analytes within the human lipidome makes it cumbersome to utilize this approach for high throughput screening.

A Method and Device for the Estimation of Blood Glucose Concentration from Signals of Sensors Implanted in Tissues

Diabetes is a major disease affecting all populations and age groups, and society as a whole. All therapies for diabetes are based on achieving close glucose control. Close glucose control achieved by sufficient and timely administration of therapy has been shown to reduce the destructive “long-term complications” of diabetes, such as retinal damage, kidney failure, amputations, and cardiovascular damage, as well as debilitating and life-threatening short-term hypoglycemia. However, attainment of close control requires a means of glucose monitoring and means for correction of glucose imbalances such as administration of insulin, pharmaceuticals, diet adjustment, and exercise, based on the monitored glucose concentration.

Combination Immunotherapies for Treatment of Liver Cancer

Primary liver cancer, with the majority being hepatocellular carcinoma (HCC), is now the second leading cause of cancer mortality and the fifth most common cancer worldwide, claiming approximately 800,000 life every year. HCC is a chemotherapy resistant tumor with limited treatment options including surgical resection, liver transplantation and local ablation at the early stages. Sorafenib, a multi-kinase inhibitor, remains a first-line systemic drug for advanced HCC even with poor outcomes, and similar low therapeutic benefits were reported for regorafenib, lenvatinib, and cabozantinib. Over 100 clinical trials that tested other compounds or approaches have failed to show therapeutic benefit to HCC patients. Immunotherapy by blocking inhibitory pathways in T lymphocytes, such as the PD-L1/PD-1 axis, is being widely tested in various solid tumors. Notably, this emerging therapeutic approach is already in clinical trials for advanced HCC in multi-centers around the globe. Two latest reports on open-label, non-randomized, phase 1/2 trials with pembrolizumab or nivolumab indicated manageable safety in advanced HCC patients with or without prior sorafenib treatment, albeit with very limited therapeutic benefits observed so far. The outcome of immunotherapy for liver cancer can be compounded by the unique immunotolerant microenvironment in the liver. A variety of clinical trials are ongoing to evaluate combination of immune checkpoint inhibitors or with other drugs, without clear justification or support by preclinical data.

MiR-22 as a Potential Treatment Target for Steatohepatitis and Type 2 Diabetes Mellitus

Researchers at the University of California, Davis have developed miR-22 inhibitors as a potential treatment for metabolic syndrome.

Three-Step Method For Universal Enrichment, Expansion, And Maturation Of Skeletal Muscle Cells Derived From Human Pluripotent Stem Cells

UCLA researchers have developed a novel method for enriching, expanding, and maturing populations of skeletal muscle progenitor cells (SMPCs) from human pluripotent stem cells (hPSCs).

Microbiome And Microbiome Derived Metabolic Products As Modifiers Of Appetite And Treatments For Obesity And Metabolic Diseases Alone Or In Combination With Existing Weight Loss Interventions

UCLA researchers in the Department of Medicine at the David Geffen School of Medicine have developed a novel treatment strategy for obesity and metabolic syndromes to improve outcomes of weight loss interventions, especially sleeve gastrectomy and gastric bypass.

Methods And Devices for Continuous Analyte Sensing with Microporous Annealed Particle Gels

UCLA researchers in the Department of Bioengineering have developed novel microporous annealed particle gels for long-term continuous monitoring of blood metabolites.

The Use Of Parathyroid Gland Cells And Their Secreted Factors To Promote Islet Beta Cell Engraftments

This invention identifies a novel method to increases survival of transplanted islets in extra-hepatic sites (subcutaneous and intramuscular) through co-transplantation of pancreatic islet beta cells together with parathyroid glands (PTGs). This treatment can successfully be used for patients with type I diabetes.

Identification Of OLMAINC as a Biomarker for NAFLD, NASH, Metabolic Syndrome, Hepatic Fibrosis

UCLA researchers in the Departments of Medicine and Human Genetics have identified a sequence of long, non-coding RNA that plays a role in the regulation of intracellular lipogenesis and holds potential for diagnosing and treating metabolic diseases, including NAFLD and NASH.

AGPAT5 as a Molecular Mediator of Insulin Resistance

UCLA researchers in the Departments of Medicine and Cardiology have identified a novel gene and pathway in the regulation of insulin sensitivity and discovered an inhibitor of this gene useful for treating AGPAT5-related diseases.

High Frequency Digital Frequency Domain Fluorescence Lifetime Imaging System For Applications On Tissues

The technology is a software/hardware combination designed to enhance sampling rate for frequency domain fluorescence lifetime imaging. Fluorescence lifetime imaging microscopy (FLIM) is a technique that uses signals emitted from fluorescent samples to construct images of those samples in near real time. An advantage to FLIM is its ability to image large fields of view, which makes it an attractive option for dynamical measurements of live biological tissues. The higher sampling rate available using this technology will allow for more information to be gleaned from biological samples, which may have a fluorescence band up to 1 GHz, advancing tissue imaging.

TREATING TYPE-1 DIABETES BY PRESERVING BETA CELL FUNCTION

This invention proposes the first pharmacological treatment to prevent the onset of Type I diabetes by preventing beta cell destruction. 

Novel Anti-Bacterial, Anti-Fungal Nanopillared Surface

Medical devices are susceptible to contamination by harmful microbes, such as bacteria and fungi, which form biofilms on device surfaces. These biofilms are often resistant to antibiotics and other current treatments, resulting in over 2 million people per year suffering from diseases related to these contaminating microbes. Death rates for many of these diseases are high, often exceeding 50%. Researchers at UCI have developed a novel anti-bacterial and anti-fungal biocomposite that incorporates a nanopillared surface structure that can be applied as a coating to medical devices.

A Method for Inhibition of de novo Lipogenesis

The obesity epidemic currently afflicting the US and other developed countries has resulted in a marked increase in the incidence of the metabolic syndrome and its associated pathologies, including nonalcoholic fatty liver disease (NAFLD), estimated to affect 30% of Americans. Although NAFLD is characterized by lipid droplet buildup in hepatocytes, it is not accompanied by liver damage, inflammation, and fibrosis unless combined with other risk factors, such as endoplasmic reticulum (ER) stress or mitochondrial dysfunction. In the context of simple, nonsymptomatic liver steatosis, ER stress or mitochondrial dysfunction trigger nonalcoholic steatohepatits (NASH), a serious disease that can progress to liver cirrhosis, resulting in loss of liver function, and hepatocellular carcinoma (HCC), one of the most deadly cancers. The obesity epidemic currently afflicting the US and other developed countries has resulted in a marked increase in the incidence of the metabolic syndrome and its associated pathologies, including nonalcoholic fatty liver disease (NAFLD), estimated to affect 30% of Americans. Although NAFLD is characterized by lipid droplet buildup in hepatocytes, it is not accompanied by liver damage, inflammation, and fibrosis unless combined with other risk factors, such as endoplasmic reticulum (ER) stress or mitochondrial dysfunction. In the context of simple, nonsymptomatic liver steatosis, ER stress or mitochondrial dysfunction trigger nonalcoholic steatohepatits (NASH), a serious disease that can progress to liver cirrhosis, resulting in loss of liver function, and hepatocellular carcinoma (HCC), one of the most deadly cancers.

Pancreatic Differentiation Process

Diabetes is an autoimmune disease in which the immune system attacks and destroys the insulin-producing beta cells in the pancreas. Islet transplantation is a suitable therapy for diabetes, but the scarceness of islet donors makes this approach practically impossible in a higher scale. Promising alternative cell sources for treating diabetes comes from human embryonic stem cells (hESCs), and numerous groups have generated functional insulin-producing cells in vitro using stepwise differentiation protocols that mimic pancreatic development, including from diabetic patients. However, the limited transcriptomic data on these cells indicate that there remain marked differences between the most mature hESC-derived cells and primary human adult beta cells. Therefore, improvements in methodologies for proper maturation of beta-cells in vitro continues to be an intense area of research.

Diagnosis and Treatment of Inflammatory Disease by Glycan Profiling of High Density Lipoprotein (HDL)

Researchers at the University of California, Davis have developed a method for diagnosing an individual patient’s risk of inflammatory disease based on glycan profiling of high density lipoprotein (HDL). The resulting profile is then used to recommend a treatment program of dietary, lifestyle, or pharmaceutical interventions (or combination thereof), to improve health and decrease the risk of inflammation-induced disease by modulating the patient’s HDL glycosylation pattern.

Sieve Container For Contactless Media Exchange For Cell Growth

Media that contains nutrients and growth factors is necessary to grow all types of cells, a process that is widely used in many fields of research. Such media should be routinely changed either to different media or a fresh batch of the same media. This change currently involves either using a pipette to transfer cells from their current dish of media to a new dish, or aspirating the media out of the dish and replacing it with new media. Both methods have inherent risks to stressing and damaging the cells. Researchers at UCI have developed a unique dish for growing cells that allows for safer aspiration of the old media, which reduces stress and damage to the cells.

Label Free Assessment Of Embryo Vitality

Researchers at UC Irvine developed an independent non-invasive method to distinguish between healthy and unhealthy embryos.

Hybridoma Producing Antibodies To C1qRp

Individuals with genetic immunodeficiency, as well as patients with HIV, cancer, and those undergoing chemotherapy or high risk surgery, are at increased risk for infection. C1q, an important component of the immune system, is known to enhance phagocytosis (cell ingestion of harmful bacteria or other materials). Scientists at UCI have developed antibodies to the receptor for C1q, C1qRp, to be used as a target for prophylactic treatments in populations at high risk of infection.

Compositions for Enhancing Beta Cell Maturation, Health, and Function

Beta cell failure is the central cause of type-2 diabetes. Researchers at UCI have developed molecules for treating diabetes that target proteins on the surface of beta cells and induce their clustering. This clustering results in an increase in insulin secretion and content and promotion of beta cell maturation. Furthermore, the clustering effect seen with these compositions may promote both proliferation and the reversal of de-differentiation.

Small Molecule Generation of Multinucleated and Striated Myofibers from Human Pluripotent Stem Cells Equivalent to Adult Skeletal Muscle

Researchers in the UCLA Department of Microbiology, Immunology and Molecular Genetics have developed a novel means of generating adult skeletal muscle-equivalent myofibers from human pluripotent stem cells.

Antibody-Targeted Mammalian Sterol Regulatory Element Binding Proteins (SREBP) 1 and 2

Sterol Regulatory Element Binding Proteins (SREBP) are important factors that control lipid homeostasis in mammals. Researchers at UCI have prepared antibodies that have good affinity and specificity for human SREBP1/2 for use as research tools. These antibodies have application in genetic and immunotherapeutic research areas.

Enhanced Cell/Bead Encapsulation Via Acoustic Focusing

The invention consists of a multi-channel, droplet-generating microfluidic device with a strategically placed feature. The feature vibrates in order to counteract particle-trapping micro-vortices formed in the device. Counteracting these vortices allows for single particle encapsulation in the droplets formed by the device and makes this technology a good candidate for use in single cell diagnostics and drug delivery systems.

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