Drug Sensitivity and Drug Repurposing Platform for Cancer Precision Medicine
Adv Exp Med Biol. 2021 Feb 25. doi: 10.1007/5584_2021_622. Online ahead of print.ABSTRACTOne of the critical Global challenges in achieving the UN Sustainable Development Goals 3 Good Health and Well Being is optimizing drug discovery and translational research for unmet medical need in both communicable and non-communicable diseases. Recently, the WHO reports there has been a shift from communicable diseases to non-communicable diseases with respect to being the leading cause of death globally and particularly in low- and middle-income countries such as South Africa. Hence, there is current drive to establish functional p...
Source: Advances in Experimental Medicine and Biology - February 25, 2021 Category: Research Authors: Ekene Emmanuel Nweke Deepak B Thimiri Govindaraj Source Type: research

Cartilage Repair by Mesenchymal Stem Cell-Derived Exosomes: Preclinical and Clinical Trial Update and Perspectives
Adv Exp Med Biol. 2021 Feb 25. doi: 10.1007/5584_2021_625. Online ahead of print.ABSTRACTOsteoarthritis (OA) and other degenerative joint diseases are characterized by articular cartilage destruction, synovial inflammation, sclerosis of subchondral bone, and loss of extracellular matrix (ECM). Worldwide, these diseases are major causes of disability. Cell therapies have been considered to be the best therapeutic strategies for long-term treatment of articular cartilage diseases. It has been suggested that the mechanism of stem cell-based therapy is related to paracrine secretion of extracellular vesicles (EVs), which are r...
Source: Advances in Experimental Medicine and Biology - February 25, 2021 Category: Research Authors: Leila Taghiyar Shahrbano Jahangir Mojtaba Khozaei Ravari Mohammad Amin Shamekhi Mohamadreza Baghaban Eslaminejad Source Type: research

The Potentials and Pitfalls of Using Adult Stem Cells in Cancer Treatment.
Authors: Das MK, Lunavat TR, Miletic H, Hossain JA Abstract Stem cells play a pivotal role in the developmental stages of an organism and in adulthood as well. Therefore, it is not surprising that stem cells constitute a focus of extensive research. Indeed, several decades of stem cell research have tremendously increased our knowledge on the mechanistic understandings of stem cell biology. Interestingly, revealing the fundamental principles of stem cell biology has also fostered its application for therapeutic purposes. Many of the attributes that the stem cells possess, some of which are unique, allow multifacete...
Source: Advances in Experimental Medicine and Biology - February 23, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Non-continuum Nature of Eukaryotic Transcriptional Regulation.
Authors: Poon GMK Abstract Eukaryotic transcription factors are versatile mediators of specificity in gene regulation. This versatility is achieved through mutual specification by context-specific DNA binding on the one hand, and identity-specific protein-protein partnerships on the other. This interactivity, known as combinatorial control, enables a repertoire of complex transcriptional outputs that are qualitatively disjoint, or non-continuum, with respect to binding affinity. This feature contrasts starkly with prokaryotic gene regulators, whose activities in general vary quantitatively in step with binding affi...
Source: Advances in Experimental Medicine and Biology - February 23, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Interleukin-6 Function and Targeting in Prostate Cancer.
Authors: Culig Z Abstract Interleukin-6 (IL-6) is a proinflammatory cytokine, which is involved in pathogenesis of several cancers. Its expression and function in prostate cancer have been extensively studied in cellular models and clinical specimens. High levels of IL-6 were detected in conditioned media from cells which do not respond to androgens. Increased phosphorylation of signal transducer and activator of transcription (STAT)3 factor which is induced in response to IL-6 is one of the typical features of prostate cancer. However, reports in the literature show regulation of neuroendocrine phenotype by IL-6. ...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Interleukin (IL)-7 Signaling in the Tumor Microenvironment.
Authors: Bednarz-Misa I, Bromke MA, Krzystek-Korpacka M Abstract Interleukin (IL)-7 plays an important immunoregulatory role in different types of cells. Therefore, it attracts researcher's attention, but despite the fact, many aspects of its modulatory action, as well as other functionalities, are still poorly understood. The review summarizes current knowledge on the interleukin-7 and its signaling cascade in context of cancer development. Moreover, it provides a cancer-type focused description of the involvement of IL-7 in solid tumors, as well as hematological malignancies.The interleukin has been discovered as...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

IL-10 Signaling in the Tumor Microenvironment of Ovarian Cancer.
Authors: Batchu RB, Gruzdyn OV, Kolli BK, Dachepalli R, Umar PS, Rai SK, Singh N, Tavva PS, Weaver DW, Gruber SA Abstract Unlike other malignancies, ovarian cancer (OC) creates a complex tumor microenvironment with distinctive peritoneal ascites consisting of a mixture of several immunosuppressive cells which impair the ability of the patient's immune system to fight the disease. The poor survival rates observed in advanced stage OC patients and the lack of effective conventional therapeutic options have been attributed in large part to the immature dendritic cells (DCs), IL-10 secreting regulatory T cells, tumor-a...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Targeted Delivery of IL-12 Adjuvants Immunotherapy by Oncolytic Viruses.
Authors: Vannini A, Leoni V, Campadelli-Fiume G Abstract The great hopes raised by the discovery of the immunoregulatory cytokine interleukin 12 (IL-12) as an anticancer agent were marred during early clinical experimentation because of severe adverse effects, which prompted a search for alternative formulations and routes of administration. Onco-immunotherapeutic viruses (OIVs) are wild-type or genetically engineered viruses that exert antitumor activity by causing death of the tumor cells they infect and by overcoming a variety of immunosuppressive mechanisms put in place by the tumors. OIVs have renewed the inte...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

IL-22 Signaling in the Tumor Microenvironment.
Authors: Jiang R, Sun B Abstract Interleukin (IL)-22 belongs to the IL-10 cytokine family which performs biological functions by binding to heterodimer receptors comprising a type 1 receptor chain (R1) and a type 2 receptor chain (R2). IL-22 is mainly derived from CD4+ helper T cells, CD8+ cytotoxic T cells, innate lymphocytes, and natural killer T cells. It can activate downstream signaling pathways such as signal transducer and activator of transcription (STAT)1/3/5, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

IL-23 and the Tumor Microenvironment.
Authors: Subhadarshani S, Yusuf N, Elmets CA Abstract The tumor microenvironment (TME), which assists in the development, progression, and metastasis of malignant cells, is instrumental in virtually every step of tumor development. While a healthy TME can protect against malignancy, in an unhealthy state, it can result in aberrant cellular behavior and augment tumor progression. Cytokines are one component of the TME, therefore, understanding the composition of the cytokine milieu in the tumor microenvironment is critical to understand the biology of malignant transformation. One cytokine, interleukin (IL)-23, has ...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Interleukin (IL)-24: Reconfiguring the Tumor Microenvironment for Eliciting Antitumor Response.
Authors: Ramesh R, Ahmed R, Munshi A Abstract Interleukin (IL)-24 is a member of the IL-10 family of cytokines. Due to its unique ability to function as both a tumor suppressor and cytokine, IL-24-based cancer therapy has been developed for treating a broad spectrum of human cancers. Majority of the studies reported to date have focused on establishing IL-24 as a cancer therapeutic by primarily focusing on tumor cell killing. However, the ability of IL-24 treatment on modulating the tumor microenvironment and immune response is underinvestigated. In this article, we summarize the biological and functional propertie...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Interleukin-31, a Potent Pruritus-Inducing Cytokine and Its Role in Inflammatory Disease and in the Tumor Microenvironment.
Authors: Rook AH, Rook KA, Lewis DJ Abstract Substantial new information has emerged supporting the fundamental role of the cytokine interleukin-31 (IL-31) in the genesis of chronic pruritus in a broad array of clinical conditions. These include inflammatory conditions, such as atopic dermatitis and chronic urticaria, to autoimmune conditions such as dermatomyositis and bullous pemphigoid, to the lymphoproliferative disorders of Hodgkin's disease and cutaneous T-cell lymphoma. IL-31 is produced in greatest quantity by T-helper type 2 (Th2) cells and upon release, interacts with a cascade of other cytokines and chem...
Source: Advances in Experimental Medicine and Biology - February 10, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Conventional Nanosized Drug Delivery Systems for Cancer Applications.
Authors: Vergallo C, Hafeez MN, Iannotta D, Santos HA, D'Avanzo N, Dini L, Cilurzo F, Fresta M, Di Marzio L, Christian C Abstract Clinical responses and tolerability of conventional nanocarriers (NCs) are sometimes different from those expected in anticancer therapy. Thus, new smart drug delivery systems (DDSs) with stimuli-responsive properties and novel materials have been developed. Several clinical trials demonstrated that these DDSs have better clinical therapeutic efficacy in the treatment of many cancers than free drugs. Composition of DDSs and their surface properties increase the specific targeting of ther...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Homing Peptides for Cancer Therapy.
Authors: Lingasamy P, Teesalu T Abstract Tumor-homing peptides are widely used for improving tumor selectivity of anticancer drugs and imaging agents. The goal is to increase tumor uptake and reduce accumulation at nontarget sites. Here, we describe current approaches for tumor-homing peptide identification and validation, and provide comprehensive overview of classes of tumor-homing peptides undergoing preclinical and clinical development. We focus on unique mechanistic features and applications of a recently discovered class of tumor-homing peptides, tumor-penetrating C-end Rule (CendR) peptides, that can be used...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Radiolabeling of Theranostic Nanosystems.
Authors: Das S, Imlimthan S, Airaksinen AJ, Sarparanta M Abstract In the recent years, progress in nanotechnology has significantly contributed to the development of novel pharmaceutical formulations to overcome the drawbacks of conventional treatments and improve the therapeutic outcome in many diseases, especially cancer. Nanoparticle vectors have demonstrated the potential to concomitantly deliver diagnostic and therapeutic payloads to diseased tissue. Due to their special physical and chemical properties, the characteristics and function of nanoparticles are tunable based on biological molecular targets and spe...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Boosting Nanomedicine Efficacy with Hyperbaric Oxygen Therapy.
Authors: Wang X, Li S, Liu X, Wu X, Ye N, Yang X, Li Z Abstract Nanomedicine has been a hot topic in the field of tumor therapy in the past few decades. Because of the enhanced permeability and retention effect (EPR effect), nanomedicine can passively yet selectively accumulate at tumor tissues. As a result, it can improve drug concentration in tumor tissues and reduce drug distribution in normal tissues, thereby contributing to enhanced antitumor effect and reduced adverse effects. However, the therapeutic efficacy of anticancer nanomedicine is not satisfactory in clinical settings. Therefore, how to improve the c...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Mesoporous Silica Nanoparticles as Carriers for Biomolecules in Cancer Therapy.
Authors: Küçüktürkmen B, Rosenholm JM Abstract Mesoporous silica nanoparticles (MSNs) offer many advantageous properties for applications in the field of nanobiotechnology. Loading of small molecules into MSNs is straightforward and widely applied, but with the upswing of both research and commercial interest in biological drugs in recent years, also biomacromolecules have been loaded into MSNs for delivery purposes. MSNs possess many critical properties making them a promising and versatile carrier for biomacromolecular delivery. In this chapter, we review the effects of the various stru...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Clearable Nanoparticles for Cancer Photothermal Therapy.
Authors: Zhao J, Long X, Zhou M Abstract Nanoparticles are important mediators for cancer photothermal therapy (PTT) where they can efficiently convert photon energy into heat and ablate the surrounding cancer cells with superior spatial and temporal precision. Recent decades have witnessed a booming development of numerous formulations of PTT nanoparticles that exhibit outstanding anti-tumor efficacy in preclinical studies. However, their clinical translation has been mined by safety concerns, especially their long-term impact on human body. Biodegradable nanoparticles that can be excreted after PTT, therefore, ar...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Biohybrid Nanosystems for Cancer Treatment: Merging the Best of Two Worlds.
Authors: Fontana F, Bartolo R, Santos HA Abstract During the last 20+ years, research into the biomedical application of nanotechnology has helped in reshaping cancer treatment. The clinical use of several passively targeted nanosystems resulted in improved quality of care for patients. However, the therapeutic efficacy of these systems is not superior to the original drugs. Moreover, despite extensive investigations into actively targeted nanocarriers, numerous barriers still remain before their successful clinical translation, including sufficient bloodstream circulation time and efficient tumor targeting. The co...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Electrospun Nanofibers for Cancer Therapy.
Authors: Luo H, Jie T, Zheng L, Huang C, Chen G, Cui W Abstract Lately, a remarkable progress has been recorded in the field of electrospinning for the preparation of numerous types of nanofiber scaffolds. These scaffolds present some remarkable features including high loading capacity and encapsulation efficiency, superficial area and porosity, potential for modification, structure for the co-delivery of various therapies, and cost-effectiveness. Their present and future applications for cancer diagnosis and treatment are promising and pioneering. In this chapter we provide a comprehensive overview of electrospun ...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Nanoneedle-Based Materials for Intracellular Studies.
Authors: Sero JE, Stevens MM Abstract Nanoneedles, defined as high aspect ratio structures with tip diameters of 5 to approximately 500 nm, are uniquely able to interface with the interior of living cells. Their nanoscale dimensions mean that they are able to penetrate the plasma membrane with minimal disruption of normal cellular functions, allowing researchers to probe the intracellular space and deliver or extract material from individual cells. In the last decade, a variety of strategies have been developed using nanoneedles, either singly or as arrays, to investigate the biology of cancer cells in vitro a...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

In Vitro Assays for Nanoparticle-Cancer Cell Interaction Studies.
Authors: Bauleth-Ramos T, Sarmento B Abstract Nanotechnology is a rapid-growing field with an extreme potential to revolutionize cancer treatments. However, despite the rapid advances, the clinical translation is still scarce. One of the main hurdles contributing for this setback is the lack of reliable in vitro models for preclinical testing capable of predicting the outcomes in an in vivo setting. In fact, the use of 2D monolayers, considered the gold-standard in vitro technique, leads to the creation of misleading data that might not be completely observed in in vivo or clinical setting. Thus, there is the need ...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles.
Authors: Daunys S, Janonienė A, Januškevičienė I, Paškevičiūtė M, Petrikaitė V Abstract The anticancer activity of compounds and nanoparticles is most often determined in the cell monolayer. However, three-dimensional (3D) systems, such as tumor spheroids, are more representing the natural tumor microenvironment. They have been shown to have higher invasiveness and resistance to cytotoxic agents and radiotherapy compared to cells growing in 2D monolayer. Furthermore, to improve the prediction of clinical efficacy of drugs, in the past decades, even more sophisticated systems, such as multicellu...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

In Vitro and In Vivo Tumor Models for the Evaluation of Anticancer Nanoparticles.
Authors: Abreu TR, Biscaia M, Gonçalves N, Fonseca NA, Moreira JN Abstract Multiple studies about tumor biology have revealed the determinant role of the tumor microenvironment in cancer progression, resulting from the dynamic interactions between tumor cells and surrounding stromal cells within the extracellular matrix. This malignant microenvironment highly impacts the efficacy of anticancer nanoparticles by displaying drug resistance mechanisms, as well as intrinsic physical and biochemical barriers, which hamper their intratumoral accumulation and biological activity.Currently, two-dimensional cell cultu...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Nanotechnology for the Development of Nanovaccines in Cancer Immunotherapy.
Authors: Grimaudo MA Abstract Up until now, surgery, radiation, and chemotherapy remain the conventional methods used in cancer treatment. However, these treatments are widely associated with severe side effects due to toxicity on normal cells. Consequently, there is an urgent need for novel therapeutic approaches that are able to effectively and selectively target tumor cells without any adverse effects on normal cells. Among the new approaches, cancer immunotherapy seems promising in the fight against tumors thanks to its prolonged efficacy and lower toxicity compared to the traditional treatments.Research studie...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Viral Nanoparticles: Cancer Vaccines and Immune Modulators.
Authors: Fusciello M, Ylösmäki E, Cerullo V Abstract In the last decades, viruses have gained great interest in the field of immuno-oncology (I-O) for their ability of interacting both with the immune system and the tumour microenvironment. Those pathogens have naturally evolved and been evolutionary to specifically infect hosts, replicate, deliver their genome, and spread. These properties, initially considered a disadvantage, have been investigated and edited to turn viruses into precious allies for molecular biology serving as gene therapy vectors, adjuvants for the immune system, drug cargos, and, lat...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Industrial Perspective on Immunotherapy.
Authors: Ravasio S Abstract Immunotherapy has revolutionised oncology and represents a fast-growing area of new drug products in anti-cancer therapy. Patients can now benefit from an expanded landscape of treatment options for several tumour types. The value of cancer immunotherapy is well-established thanks to the clinical success following regulatory approval of several immunomodulators and cellular immunotherapies, and both the private and the public sector are investing to provide patients with improved immune-based agents and to extend the indications of already marketed products. Although recent achievements ...
Source: Advances in Experimental Medicine and Biology - February 7, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Constituents of Cannabis sativa.
Authors: Echeverry C, Reyes-Parada M, Scorza C Abstract Cannabis sativa L. is a psychoactive plant that contains more than 500 chemical components. Even though the consumption (in the form of marijuana, hashish, or hashish oil) for recreational purposes, is the most popular way of using the plant, the knowledge of its components has also led to classify Cannabis sativa L. is a plant with medicinal or therapeutical use. Several comprehensive reviews have already been published focused on the chemical composition of Cannabis sativa. In this chapter, we will summarize relevant information about those components, which...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Synthetic and Natural Derivatives of Cannabidiol.
Authors: Morales P, Jagerovic N Abstract The non-psychoactive component of Cannabis Sativa, cannabidiol (CBD), has centered the attention of a large body of research in the last years. Recent clinical trials have led to the FDA approval of CBD for the treatment of children with drug-resistant epilepsy. Even though it is not yet in clinical phases, its use in sleep-wake pathological alterations has been widely demonstrated.Despite the outstanding current knowledge on CBD therapeutic effects in numerous in vitro and in vivo disease models, diverse questions still arise from its molecular pharmacology. CBD has been sh...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Clinical Pharmacokinetics of Cannabinoids and Potential Drug-Drug Interactions.
Authors: Vázquez M, García-Carnelli C, Maldonado C, Fagiolino P Abstract Over the past few years, considerable attention has focused on cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the two major constituents of Cannabis sativa, mainly due to the promising potential medical uses they have shown. However, more information on the fate of these cannabinoids in human subjects is still needed and there is limited research on the pharmacokinetic drug-drug interactions that can occur in the clinical setting and their prevalence. As the use of cannabinoids is substantially increasing for many ind...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cannabinoid Receptors and Ligands: Lessons from CNS Disorders and the Quest for Novel Treatment Venues.
Authors: Vecchini Rodríguez CM, Escalona Meléndez Y, Flores-Otero J Abstract The potential use of cannabinoids for therapeutic purposes is at the forefront of cannabinoid research which aims to develop innovative strategies to prevent, manage and treat a broad spectrum of human diseases. This chapter briefly reviews the pivotal role of the endocannabinoid system in modulating the central nervous system and its roles on neurodegenerative diseases and brain disorders. Ligand-induced modulation of cannabinoid 1 and 2 receptors to modulate immune response, decrease neurodegeneration and pain are aspe...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Sleep-Wake Neurobiology.
Authors: Vanini G, Torterolo P Abstract Sleep and wakefulness are complex, tightly regulated behaviors that occur in virtually all animals. With recent exciting developments in neuroscience methodologies such as optogenetics, chemogenetics, and cell-specific calcium imaging technology, researchers can advance our understanding of how discrete neuronal groups precisely modulate states of sleep and wakefulness. In this chapter, we provide an overview of key neurotransmitter systems, neurons, and circuits that regulate states of sleep and wakefulness. We also describe long-standing models for the regulation of sleep/w...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cannabinoids and Sleep/Wake Control.
Authors: Méndez-Díaz M, Ruiz-Contreras AE, Cortés-Morelos J, Prospéro-García O Abstract The sleep-wake cycle is a complex process that includes wake (W), non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Each phase is regulated by specialized brain structures that, by means of different neurotransmitters, maintain the constant expression of the sleep-wake cycle. Molecules like orexin, serotonin, noradrenaline, histamine, for waking; GABA, adenosine, prostaglandins, for NREM sleep and acetylcholine and glutamate for REM sleep, among other molecules are responsible f...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Effects of Cannabinoid Agonists and Antagonists on Sleep in Laboratory Animals.
Authors: Petrunich-Rutherford ML, Calik MW Abstract The cannabinoids are a family of chemical compounds that can be either synthesized or naturally derived. These compounds have been shown to modulate a wide variety of biological processes. In this chapter, the studies detailing the effects of cannabinoids on sleep in laboratory animals are reviewed. Both exogenous and endogenous cannabinoids generally appear to decrease wakefulness and alter rapid eye movement (REM) and non-REM sleep in animal models. In addition, cannabinoids potentiate the effects of sedative-hypnotic drugs. However, the individual contributions...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Modulation of Noradrenergic and Serotonergic Systems by Cannabinoids: Electrophysiological, Neurochemical and Behavioral Evidence.
Authors: Mendiguren A, Aostri E, Pineda J Abstract The main noradrenergic and serotonergic nuclei in the central nervous system (CNS) are the locus coeruleus (LC) and the dorsal raphe nucleus (DRN). These brain areas, located in the brainstem, play a pivotal role in the control of various functions and behaviors that are altered by cannabinoids (i.e., pain, arousal, mood, anxiety, or sleep-wake cycle). Anatomical, neurochemical, and functional data suggest that cannabinoids regulate both central noradrenergic and serotonergic neurotransmission. Thus, strong evidence has shown that the firing activity of LC and DRN ...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Natural Cannabinoids as Templates for Sleep Disturbances Treatments.
Authors: Murillo-Rodríguez E, Machado S, Imperatori C, Yamamoto T, Budde H Abstract The sleep-wake cycle is a complex composition of specific physiological and behavioral characteristics. In addition, neuroanatomical, neurochemical and molecular systems exerts influences in the modulation of the sleep-wake cycle. Moreover, homeostatic and circadian mechanisms interact to control the waking or sleeping states. As many other behaviors, sleep also develops pathological features that include several signs and symptoms corresponding to medical conditions known as sleep disorders.In addition to the neurobiological...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Effect of Cannabinoids on the Brain's Circadian Clock.
Authors: Acuna Goycolea C Abstract The circadian rhythm is without a doubt the main element influencing the way human lead their lives. Emerging evidence indicate that cannabinoids affect these routines by regulating neuronal firing within the suprachiasmatic nucleus, the master circadian pacemaker in the brain. These actions of cannabinoids on the brain's clock may also underlie time-wraps commonly experienced by marijuana users. PMID: 33537942 [PubMed - in process] (Source: Advances in Experimental Medicine and Biology)
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Effects of Cannabis Consumption on Sleep.
Authors: Mondino A, Cavelli M, González J, Murillo-Rodriguez E, Torterolo P, Falconi A Abstract Despite the fact that medical properties of Cannabis have been recognized for more than 5000 years, the use of Cannabis for medical purposes have recently reemerged and became more accessible. Cannabis is usually employed as a self-medication for the treatment of insomnia disorder. However, the effects of Cannabis on sleep depend on multiple factors such as metabolomic composition of the plant, dosage and route of administration. In the present chapter, we reviewed the main effect Cannabis on sleep. We focused on ...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Addiction and Sleep Disorders.
Authors: Ek J, Jacobs W, Kaylor B, McCall WV Abstract Shared neurophysiology of addiction and sleep disorders results in a bidirectional interplay. Diagnosing and treating primary sleep disorders, particularly in adolescents, can prevent the development of addiction in susceptible individuals. Addressing sleep issues in early recovery, and throughout maintenance, can prevent relapse. Cannabis use for insomnia shows mixed results; assisting with onset sleep latency in early use, this subsides with chronic use and holds addiction risk. Insomnia is a primary complaint of cannabis withdrawal syndrome and a primary caus...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Cannabis for Restless Legs Syndrome.
Authors: Ghorayeb I Abstract Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by an urge to move the legs. This urge is often accompanied by pain or other uncomfortable and unpleasant sensations, it either occurs or worsens during rest, particularly in the evening and/or at night, and temporarily improves with activity. Affecting nearly 3% of the North American and European populations in its moderate-to-severe form, RLS has a considerable negative impact on the quality of life, and sleep and is associated with significant morbidity. Although new developments have deepened our understan...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Protein Kinase-Mediated Decision Between the Life and Death.
Authors: Engin A Abstract Protein kinases are intracellular signaling enzymes that catalyze the phosphorylation of specific residues in their target substrate proteins. They play important role for regulation of life and death decisions. The complexity of the relationship between death receptors and protein kinases' cell death decision-making mechanisms create many difficulties in the treatment of various diseases. The most of fifteen different cell death pathways, which are reported by Nomenclature Committee on Cell Death (NCCD) are protein kinase signal transduction-mediated negative or positive selections. Tumor...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Aging and Protein Kinases.
Authors: Engin AB, Engin A Abstract Recently, aging has been tried to be explained with large numbers of theories, but none of them can elucidate the changes occurring in the aging process alone. A unified theory encompassing the mechanisms of genetic factors and repair systems in aging is becoming increasingly required. Almost 37 protein kinases contribute to all processes of aging and senescence. Furthermore, these kinases not only regulate the large number of metabolic pathways related to aging processes, but also control these pathways through 12 checkpoints. Thus, in this chapter, the metabolic targets of prot...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

The Connection Between Cell Fate and Telomere.
Authors: Engin AB, Engin A Abstract Abolition of telomerase activity results in telomere shortening, a process that eventually destabilizes the ends of chromosomes, leading to genomic instability and cell growth arrest or death. Telomere shortening leads to the attainment of the "Hayflick limit", and the transition of cells to state of senescence. If senescence is bypassed, cells undergo crisis through loss of checkpoints. This process causes massive cell death concomitant with further telomere shortening and spontaneous telomere fusions. In functional telomere of mammalian cells, DNA contains double-stra...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Dark-Side of Exosomes.
Authors: Engin A Abstract Exosomes are nanoscale extracellular vesicles that can transport cargos of proteins, lipids, DNA, various RNA species and microRNAs (miRNAs). Exosomes can enter cells and deliver their contents to recipient cell. Owing to their cargo exosomes can transfer different molecules to the target cells and change the phenotype of these cells. The fate of the contents of an exosome depends on its target destination. Various mechanisms for exosome uptake by target cells have been proposed, but the mechanisms responsible for exosomes internalization into cells are still debated. Exosomes exposed cell...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Signal Transduction in Immune Cells and Protein Kinases.
Authors: Neagu M, Constantin C Abstract Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner.In innate system, Toll-like receptor signaling is the main molecular event triggering effector functi...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Role of Protein Kinase C in Immune Cell Activation and Its Implication Chemical-Induced Immunotoxicity.
Authors: Corsini E, Buoso E, Galbiati V, Racchi M Abstract Protein kinase C (PKCs) isoforms play a key regulatory role in a variety of cellular functions, including cell growth and differentiation, gene expression, hormone secretion, etc. Patterns of expression for each PKC isoform differ among tissues, and it is also clear that different PKCs are often not functionally redundant, for example specific PKCs mediate specific cellular signals required for activation, proliferation, differentiation and survival of immune cells. In the last 20 years, we have been studying the role of PKCs, mainly PKCβ and its ...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Combined Toxicity of Metal Nanoparticles: Comparison of Individual and Mixture Particles Effect.
Authors: Engin AB Abstract Toxicity of metal nanoparticles (NPs) are closely associated with increasing intracellular reactive oxygen species (ROS) and the levels of pro-inflammatory mediators. However, NP interactions and surface complexation reactions alter the original toxicity of individual NPs. To date, toxicity studies on NPs have mostly been focused on individual NPs instead of the combination of several species. It is expected that the amount of industrial and highway-acquired NPs released into the environment will further increase in the near future. This raises the possibility that various types of NPs co...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.
Authors: Engin AB, Engin A Abstract Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and β-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, β-cell dysfunction or β-cell death initiates the deleterious vicious cycle observed in T2D. Although the primary cause is still unknown, overnutrition that contributes to the induction of the state of low-grade inflammation, and the activation of various protein kinases-related metabolic pathways are main factors leading ...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

Bile Acid Toxicity and Protein Kinases.
Authors: Engin A Abstract If the bile acids reach to pathological concentrations due to cholestasis, accumulation of hydrophobic bile acids within the hepatocyte may result in cell death. Thus, hydrophobic bile acids induce apoptosis in hepatocytes, while hydrophilic bile acids increase intracellular adenosine 3',5'-monophosphate (cAMP) levels and activate mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways to protect hepatocytes from apoptosis.Two apoptotic pathways have been described in bile acids-induced death. Both are controlled by multiple protein kinase signaling pathways. ...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research

N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.
Authors: Engin A, Engin AB Abstract Although stroke is very often the cause of death worldwide, the burden of ischemic and hemorrhagic stroke varies between regions and over time regarding differences in prognosis, prevalence of risk factors, and treatment strategies. Excitotoxicity, oxidative stress, dysfunction of the blood-brain barrier, neuroinflammation, and lysosomal membrane permeabilization, sequentially lead to the progressive death of neurons. In this process, protein kinases-related checkpoints tightly regulate N-methyl-D-aspartate (NMDA) receptor signaling pathways. One of the major hallmarks of cerebra...
Source: Advances in Experimental Medicine and Biology - February 6, 2021 Category: Research Tags: Adv Exp Med Biol Source Type: research