Enhanced Extracellular Vesicle Cargo Loading via microRNA Biogenesis Pathway Modulation.

Extracellular vesicles (EVs) are physiological vectors for the intercellular transport of a variety of molecules. Among these, small RNAs, and especially microRNAs (miRNAs), have been identified as prevalent components, and there has thus been a robust investigation of EVs for therapeutic miRNAs delivery. However, intrinsic levels of EV-associated miRNAs are generally too low to enable efficient and effective therapeutic outcomes.

Combinatorial microRNA Loading into Extracellular Vesicles for Increased Anti-Inflammatory Efficacy.

Extracellular vesicles (EVs) have emerged as promising therapeutic entities in part due to their potential to regulate multiple signaling pathways in target cells. This potential is derived from the broad array of constituent and/or cargo molecules associated with EVs. Among these, microRNAs (miRNAs) are commonly implicated as important and have been associated with a wide variety of EV-induced biological phenomena.

Bacterial chemotaxis in static gradients quantified in a biopolymer membrane-integrated microfluidic platform.

Chemotaxis is a fundamental bacterial response mechanism to changes in chemical gradients of specific molecules known as chemoattractant or chemorepellent. The advancement of biological platforms for bacterial chemotaxis research is of significant interest for a wide range of biological and environmental studies. Many microfluidic devices have been developed for its study, but challenges still remain that can obscure analysis.

Therapeutic Potential of Extracellular Vesicles for Sepsis Treatment.

Sepsis is a deadly condition lacking a specific treatment despite decades of research. This has prompted the exploration of new approaches, with extracellular vesicles (EVs) emerging as a focal area. EVs are nanosized, cell-derived particles that transport bioactive components (i.

Homologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in .

We developed a hybrid synthetic circuit that co-opts the genetic regulation of the native bacterial quorum sensing autoinducer-2 and imposes an extra external controller for maintaining tightly controlled gene expression. This dual-input genetic controller was mathematically modeled and, by design, can be operated in three modes: a constitutive mode that enables consistent and high levels of expression; a tightly repressed mode in which there is very little background expression; and an inducible mode in which concentrations of two signals (arabinose and autoinducer-2) determine the net amplification of the gene(s)-of-interest. We demonstrate the utility of the circuit for the controlled expression of human granulocyte macrophage colony stimulating factor in an engineered probiotic .

Protein-based vehicles for biomimetic RNAi delivery.

Broad translational success of RNA interference (RNAi) technology depends on the development of effective delivery approaches. To that end, researchers have developed a variety of strategies, including chemical modification of RNA, viral and non-viral transfection approaches, and incorporation with delivery vehicles such as polymer- and lipid-based nanoparticles, engineered and native proteins, extracellular vesicles (EVs), and others. Among these, EVs and protein-based vehicles stand out as biomimetically-inspired approaches, as both proteins (e.

A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease.

For therapies targeting diseases of the gastrointestinal tract, we and others envision probiotic bacteria that synthesize and excrete biotherapeutics at disease sites. Toward this goal, we have engineered commensal E. coli that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD).

Controlling localization of Escherichia coli populations using a two-part synthetic motility circuit: An accelerator and brake.

Probiotics, whether taken as capsules or consumed in foods, have been regarded as safe for human use by regulatory agencies. Being living cells, they serve as "tunable" factories for the synthesis of a vast array of beneficial molecules. The idea of reprogramming probiotics to act as controllable factories, producing potential therapeutic molecules under user-specified conditions, represents a new and powerful concept in drug synthesis and delivery.

Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling.

The ability to interconvert information between electronic and ionic modalities has transformed our ability to record and actuate biological function. Synthetic biology offers the potential to expand communication 'bandwidth' by using biomolecules and providing electrochemical access to redox-based cell signals and behaviours. While engineered cells have transmitted molecular information to electronic devices, the potential for bidirectional communication stands largely untapped.

A 12-step treatment approach for marijuana (Cannabis) dependence.

Marijuana (Cannabis) dependence (addiction) is a disorder for which treatment is essential and relatively sophisticated. A basic assumption in the treatment model is that marijuana addiction involves pathological processes in the physical, mental (cognitive), and emotional (mood) states of the addicted individual. These pathological processes constitute a disease entity that is diagnosable, treatable, and has a predictable course.

Sexual dysfunction in abusers of cocaine and alcohol.

Sexual dysfunction is not uncommon in alcoholics and in cocaine addicts. Alcohol abuse frequently develops along with cocaine dependence and the reverse is also common. We examined the sexual history of this common dually-addicted population.

Cocaine abuse, attention deficit disorder, and bipolar disorder.

Cocaine is a potent dopamine agonist that frequently stimulates the central nervous system and is often manifested by increased psychomotor activity, impulsivity, euphoria, and rapid thoughts. Attention deficit disorder (ADD) and bipolar disorder also present with physical restlessness, racing thoughts, distractibility, and mood instability. Although these three disorders rarely appear in the same individual, they are important differential diagnoses when considering any one illness with the above symptom complexes.

Eating disorders and cocaine abuse: a survey of 259 cocaine abusers.

A structured clinical interview designed to diagnose eating disorders was administered to 259 consecutive callers to the National Cocaine Hotline who met DSM-III criteria for cocaine abuse. Thirty-two percent of those surveyed met DSM-III criteria for either anorexia nervosa, bulimia, or both disorders. The prevalence rates for each of these disorders in this sample appeared elevated even when narrow diagnostic criteria were applied.

Evaluating depression in alcoholics.

The persistence of untreated depression was evaluated in 49 severely depressed alcoholics. After 2 weeks of sobriety, 80% of patients with initial major depression by Research Diagnostic Criteria were no longer depressed. These patients improved without antidepressant medications, suggesting the need for a 2-week period of sobriety before psychopharmacotherapy for depression is instituted.

Dexamethasone suppression test testing of depressed alcoholics.

In order to determine the sensitivity of the dexamethasone suppression test (DST) for major depression in alcoholics, we administered this test to 27 alcoholics with major depression. Sixteen of 27 had abnormal DST results, yielding a 59% sensitivity for depression in alcoholics. When combined with previously reported specificity findings of 100%, the DST significantly (p less than 0.

Central stimulant abuse: neurochemistry and pharmacotherapy.

This paper reviews certain clinical and neurochemical aspects of cocaine abuse. Once entrenched patterns of addiction have developed, cocaine addicts suffer progressive financial, medical, psychiatric and psychosocial deterioration that results, to some extent, from cocaine-induced neurochemical alterations in the brain. While cocaine produces euphoria through its stimulatory effect on dopamine neurons, several lines of evidence suggest that dopamine depletion occurs after chronic cocaine abuse.

Specificity of the TRH test for major depression in patients with serious cocaine abuse.

The authors administered the thyrotropin-releasing hormone (TRH) test to 17 patients with severe cocaine abuse and without major depression. The results suggest that the test is not specific for major depression when serious cocaine abuse is present.

Opiate and cocaine dependencies. Techniques to help counter the rising tide.

Clonidine (Catapres) is a safe and effective agent for detoxification of selected opiate addicts. It seems best suited for transitional treatment between opiate dependency and aftercare with naltrexone (Trexan). The current epidemic of cocaine abuse in the United States is associated with intensified usage patterns and an increased prevalence of adverse medical consequences.