Extracellular vesicles (EVs) are cell-derived membrane-enclosed particles that are involved in physiologic and pathologic processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell–derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this effect

In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium taurocholate, and the hormone secretin to stimulate bile flow led to conflicting data and a moratorium on attempts to further develop the initial proposal

Cancer is a leading cause of death worldwide, resulting in ~10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family, which consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between

Protein SUMOylation is a major post-translational modification essential for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all small ubiquitin-like modifiers (SUMOs)

The endoplasmic reticulum (ER) is the largest organelle of the cell, composed of a continuous network of sheets and tubules, and is involved in protein, calcium (Ca2+), and lipid homeostasis. In neurons, the ER extends throughout the cell, both somal and axodendritic compartments, and is highly important for neuronal functions. A third of the proteome of a cell, secreted and membrane-bound proteins

The cannabis derivative marijuana is the most widely used recreational drug in the Western world and is consumed by an estimated 83 million individuals (~3% of the world population). In recent years, there has been a marked transformation in society regarding the risk perception of cannabis, driven by its legalization and medical use in many states in the United States and worldwide. Compelling research

The two β-arrestins, β-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiologic functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors. However

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters

Despite that fact roughly 40% of all FDA approved pharmacological therapeutics target G Protein-Coupled Receptors (GPCRs), there remains a noted gap in our understanding of the physiological and functional role of these receptors at the systems level. While heterologous expression systems and in vitro assays have revealed a tremendous amount about GPCR signaling cascades, how these cascades interact

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is activated by ligand binding, overexpression, or mutation. It is well known for its tyrosine kinase-dependent oncogenic activities in a variety of human cancers. A large number of EGFR inhibitors have been developed for cancer treatment, including monoclonal antibodies, tyrosine kinase inhibitors, and a vaccine. The EGFR inhibitors

Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as

ABSTRACT Oxycodone, a semi-synthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for over 100 years. Although thebaine cannot be used therapeutically due to the occurrence of convulsions at higher doses, it has been converted to a number of other widely used compounds that include naloxone, naltrexone, buprenorphine, and oxycodone. Despite the early identification

Natural language processing (NLP) is an area of artificial intelligence that applies information technologies to process the human language, understand it to a certain degree, and use it in various applications. This area has rapidly developed in the past few years and now employs modern variants of deep neural networks to extract relevant patterns from large text corpora. The main objective of this

Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilising the loss of or modestly improving lung function, with disease progression resuming

Extracellular vesicles (EVs) are cell-derived membrane enclosed particles that are involved in physiological and pathological processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell-derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this

Cancer is a leading cause of death worldwide resulting in ~10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family that consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between Myc

Protein SUMOylation is a major post-translational modification important for maintaining cellular homeostasis. SUMOylation has long been associated with stress responses as a diverse array of cellular stress signals are known to trigger rapid alternations in global protein SUMOylation. In addition, while there are large families of ubiquitination enzymes, all SUMOs are conjugated by a set of enzymatic

The endoplasmic reticulum (ER) is the largest organelle of the cell, composed of a continuous network of sheets and tubules, and is involved in protein, calcium (Ca2+) and lipid homeostasis. In neurons, the ER extends throughout the cell, both somal and axodendritic compartments, and is highly important for neuronal functions. A third of the proteome of a cell, secreted and membrane-bound proteins

The development of cutting-edge techniques to study specific brain regions and neural circuits that regulate sleep–wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep,

The two beta-arrestins, beta-arrestin-1 and -2 (systematic names: arrestin-2 and -3, respectively), are multifunctional intracellular proteins that regulate the activity of a very large number of cellular signaling pathways and physiological functions. The two proteins were discovered for their ability to disrupt signaling via G protein-coupled receptors (GPCRs) via binding to the activated receptors

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat CNS diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solve

Lysine-selective molecular tweezers (MTs) are supramolecular host molecules displaying a remarkably broad spectrum of biologic activities. MTs act as inhibitors of the self-assembly and toxicity of amyloidogenic proteins using a unique mechanism. They destroy viral membranes and inhibit infection by enveloped viruses, such as HIV-1 and SARS-CoV-2, by mechanisms unrelated to their action on protein

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration

Several integral membrane proteins undergo regulated intramembrane proteolysis (RIP), a tightly controlled process through which cells transmit information across and between intracellular compartments. RIP generates biologically active peptides by a series of proteolytic cleavage events carried out by two primary groups of enzymes: sheddases and intramembrane-cleaving proteases (iCLiPs). Following

The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components of these experiences impact well-being. In recent years, research has suggested that classic psychedelics display the potential to promote positive enduring psychologic and behavioral changes in clinical and nonclinical populations. Paradoxically

Glycine receptors are ligand-gated ion channels that mediate synaptic inhibition throughout the mammalian spinal cord, brainstem, and higher brain regions. They have recently emerged as promising targets for novel pain therapies due to their ability to produce antinociception by inhibiting nociceptive signals within the dorsal horn of the spinal cord. This has greatly enhanced the interest in developing

Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. Despite its widespread use, we have an incomplete understanding of the way in which acute and chronic sessions of TMS affect various neural and vascular systems. This systematic review summarizes the state of our knowledge regarding the effects

Carbon monoxide (CO) has been firmly established as an endogenous signaling molecule with a variety of pathophysiological and pharmacological functions, including immunomodulation, organ protection, and circadian clock regulation, among many others. In terms of its molecular mechanism(s) of action, CO is known to bind to a large number of hemoproteins with at least 25 identified targets, including

Adenosine is an evolutionary ancient metabolic regulator linking energy state to physiologic processes, including immunomodulation and cell proliferation. Tumors create an adenosine-rich immunosuppressive microenvironment through the increased release of ATP from dying and stressed cells and its ectoenzymatic conversion into adenosine. Therefore, the adenosine pathway becomes an important therapeutic

A reliable translation of in vitro and preclinical data on drug absorption, distribution, metabolism, and excretion (ADME) to humans is important for safe and effective drug development. Precision medicine that is expected to provide the right clinical dose for the right patient at the right time requires a comprehensive understanding of population factors affecting drug disposition and response. Characterization

Metabotropic glutamate (mGlu) receptors, a family of G-protein-coupled receptors, have been identified as novel therapeutic targets based on extensive research supporting their diverse contributions to cell signaling and physiology throughout the nervous system and important roles in regulating complex behaviors, such as cognition, reward, and movement. Thus, targeting mGlu receptors may be a promising