scholarly journals Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7302
Author(s):  
Bryan Latrell Holloman ◽  
Mitzi Nagarkatti ◽  
Prakash Nagarkatti
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Cannabinoid Receptors ◽  
T Regulatory Cells ◽  
Neurological Diseases ◽  
Suppressor Cells ◽  
The Body ◽  
New Class ◽  
Wide Range ◽  
Clinical Disorders

Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative. Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

Abstract Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

scholarly journals The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

2020 ◽  
Vol 10 (6) ◽  
pp. 411-429
Author(s):  
Ayman Khalil ◽  
Diana Tazeddinova
Keyword(s):  
Viral Infections ◽  
Neurological Diseases ◽  
Large Family ◽  
Polyphenolic Compounds ◽  
The Body ◽  
New Drugs ◽  
Human Pathogens ◽  
Wide Range ◽  
Review Reports ◽  
Physiological Benefits

Abstract Polyphenols are a large family of more than 10,000 naturally occurring compounds, which exert countless pharmacological, biological and physiological benefits for human health including several chronic diseases such as cancer, diabetes, cardiovascular, and neurological diseases. Their role in traditional medicine, such as the use of a wide range of remedial herbs (thyme, oregano, rosemary, sage, mint, basil), has been well and long known for treating common respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID-19, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Thus, polyphenols ought to be considered as a potential and valuable source for designing new drugs that could be used effectively in the combat against COVID‐19 and other rigorous diseases.

Cannabinoids for Symptom Management in Patients with Kidney Failure

2022 ◽  
pp. CJN.11560821
Author(s):  
Hayley Worth ◽  
Daniel O'Hara ◽  
Neeru Agarwal ◽  
David Collister ◽  
Frank Brennan ◽  
...  
Keyword(s):  
Kidney Failure ◽  
Cannabinoid Receptors ◽  
Treatment Options ◽  
Symptom Relief ◽  
Symptom Burden ◽  
Poor Quality ◽  
The Body ◽  
Wide Range ◽  
New Treatment

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, anti-emetic, analgesic and anti-inflammatory effects. Considering their known physiological actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, while these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.

scholarly journals Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

2020 ◽  
Vol 21 (14) ◽  
pp. 4829 ◽  
Author(s):  
Beatriz Castejón-Vega ◽  
Francesca Giampieri ◽  
José M. Alvarez-Suarez
Keyword(s):  
Neurological Diseases ◽  
Adaptor Protein ◽  
The Body ◽  
Macromolecular Complex ◽  
Positive Effects ◽  
Nutraceutical Compounds ◽  
Wide Range ◽  
Inflammatory Processes ◽  
Nlrp3 Inflammasomes

The macromolecular complex known as “inflammasome” is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people’s interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term “nutraceutical” has recently emerged as a hybrid term between “nutrition” and “pharmacological” and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.

scholarly journals The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Autoimmune Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengrou Lu ◽  
Emma DiBernardo ◽  
Emily Parks ◽  
Hannah Fox ◽  
Si-Yang Zheng ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Extracellular Vesicles ◽  
Symptom Management ◽  
Cell Types ◽  
The Body ◽  
Physiological Effects ◽  
Disease Pathogenesis ◽  
Wide Range ◽  
Promising Avenue

Extracellular vesicles (EVs) are important players in autoimmune diseases, both in disease pathogenesis and as potential treatments. EVs can transport autoimmune triggers throughout the body, facilitating the process of antigen presentation. Understanding the link between cellular stress and EV biogenesis and intercellular trafficking will advance our understanding of autoimmune diseases. In addition, EVs can also be effective treatments for autoimmune diseases. The diversity of cell types that produce EVs leads to a wide range of molecules to be present in EVs, and thus EVs have a wide range of physiological effects. EVs derived from dendritic cells or mesenchymal stem cells have been shown to reduce inflammation. Since many autoimmune treatments are focused only on symptom management, EVs present a promising avenue for potential treatments. This review looks at the different roles EVs can play in autoimmune diseases, from disease pathology to diagnosis and treatment. We also overview various methodologies in isolating or generating EVs and look to the future for possible applications of EVs in autoimmune diseases.

scholarly journals Grinding tools made of grains with controlled shape and orientation

2018 ◽  
Vol 224 ◽  
pp. 01071
Author(s):  
Alexander Korotkov ◽  
Vitaly Korotkov
Keyword(s):  
Arbitrary Shape ◽  
The Body ◽  
Cutting Process ◽  
Initial Mass ◽  
Grinding Wheels ◽  
Comparative Tests ◽  
New Class ◽  
Wide Range ◽  
Electrostatic Effect

The cutting elements of the grinding tools are grains. But only a small part of the grains participates actively in the cumulative cutting process. Each grain has its own arbitrary shape and a chaotic arrangement in the body of the instrument. As a consequence, the geometry of the cutting part of the grains varies over a wide range and this greatly reduces the performance of grinding tools. A new class of tools and technology for their manufacture, in which the shape and orientation of the used grains is controlled, is proposed. The choice of a certain grains shape is ensured by separating the initial mass of the abrasive in a vibratory way into a series of fractions with the same grain form. Orientation of the grains is achieved by applying an electrostatic effect that regulates the grains position in the tool. The pilot batches of grinding wheels cutting, peeling, petal are designed and manufactured, as well as grinding skins and belts with controlled shape and orientation of the grains. Circles and tapes underwent comparative tests with standard tools and showed significant advantages in operation.

scholarly journals Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

2020 ◽  
Vol 21 (3) ◽  
pp. 723 ◽  
Author(s):  
Pierangelo Cifelli ◽  
Gabriele Ruffolo ◽  
Eleonora De Felice ◽  
Veronica Alfano ◽  
Erwin Alexander van Vliet ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Neurological Diseases ◽  
Chloride Ion ◽  
Gaba Release ◽  
New Class ◽  
Inhibitory Function ◽  
Acid Type ◽  
Wide Range ◽  
The Central Nervous System ◽  
Neurological Conditions

γ-Aminobutyric acid type A receptors (GABAARs) are the main inhibitory mediators in the central nervous system (CNS). GABAARs are pentameric ligand gated ion channels, and the main subunit composition is usually 2α2βγ, with various isotypes assembled within a set of 19 different subunits. The inhibitory function is mediated by chloride ion movement across the GABAARs, activated by synaptic GABA release, reducing neuronal excitability in the adult CNS. Several studies highlighted the importance of GABA-mediated transmission during neuro-development, and its involvement in different neurological and neurodevelopmental diseases, from anxiety to epilepsy. However, while it is well known how different classes of drugs are able to modulate the GABAARs function (benzodiazepines, barbiturates, neurosteroids, alcohol), up to now little is known about GABAARs and cannabinoids interaction in the CNS. Endocannabinoids and phytocannabinoids are lately emerging as a new class of promising drugs for a wide range of neurological conditions, but their safety as medication, and their mechanisms of action are still to be fully elucidated. In this review, we will focus our attention on two of the most promising molecules (Δ9-tetrahydrocannabinol; Δ9-THC and cannabidiol; CBD) of this new class of drugs and their possible mechanism of action on GABAARs.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A. Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

ABSTRACTAntisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing the field to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal, and non-neuronal cells. Therefore, it is critically important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and robust activity throughout the CNS in neurons, oligodendrocytes, astrocytes, and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

Creating the Wind

2020 ◽  
Vol 2 (4) ◽  
pp. 14-31
Author(s):  
Élodie Dupey García
Keyword(s):  
Indigenous Communities ◽  
The Body ◽  
Historical Sources ◽  
Natural Behavior ◽  
Sensory Experiences ◽  
Identity And Agency ◽  
Wide Range ◽  
Late Postclassic ◽  
Comparative Examination ◽  
Meteorological Phenomenon

This article explores how the Nahua of late Postclassic Mesoamerica (1200–1521 CE) created living and material embodiments of their wind god constructed on the basis of sensory experiences that shaped their conception of this divinized meteorological phenomenon. In this process, they employed chromatic and design devices, based on a wide range of natural elements, to add several layers of meaning to the human, painted, and sculpted supports dressed in the god’s insignia. Through a comparative examination of pre-Columbian visual production—especially codices and sculptures—historical sources mainly written in Nahuatl during the viceregal period, and ethnographic data on indigenous communities in modern Mexico, my analysis targets the body paint and shell jewelry of the anthropomorphic “images” of the wind god, along with the Feathered Serpent and the monkey-inspired embodiments of the deity. This study identifies the centrality of other human senses beyond sight in the conception of the wind god and the making of its earthly manifestations. Constructing these deity “images” was tantamount to creating the wind because they were intended to be visual replicas of the wind’s natural behavior. At the same time, they referred to the identity and agency of the wind god in myths and rituals.

Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases

2020 ◽  
Vol 26 (42) ◽  
pp. 5488-5502 ◽  
Author(s):  
Yub Raj Neupane ◽  
Asiya Mahtab ◽  
Lubna Siddiqui ◽  
Archu Singh ◽  
Namrata Gautam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Drug Delivery Systems ◽  
Drug Carriers ◽  
Immunological Tolerance ◽  
Delivery Systems ◽  
The Body ◽  
Autoimmune Response ◽  
Treatment Modalities

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

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