scholarly journals Novel Insights into Molecular Mechanisms of Chronic Pain

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2220
Author(s):  
Ellen Niederberger
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Special Issue ◽  
Different Types ◽  
Chronic Pain Conditions ◽  
Novel Therapeutic Strategies ◽  
Pain Patients ◽  
Novel Therapeutic

Pain is the most frequent cause triggering patients to visit a physician. The worldwide incidence of chronic pain is in the range of 20% of adults, and chronic pain conditions are frequently associated with several comorbidities and a drastic decrease in patients’ quality of life. Although several approved analgesics are available, such therapy is often not satisfying due to insufficient efficacy and/or severe side effects. Therefore, novel strategies for the development of safe and highly efficacious pain killers are urgently needed. To reach this goal, it is necessary to clarify the causes and signal transduction cascades underlying the onset and progression of the different types of chronic pain. The papers in this Special Issue cover a wide variety of mechanisms involved in different pain types such as inflammatory, neuropathic or cancer pain. Therefore, the results summarized here might contribute to a better understanding of the mechanisms in chronic pain and thereby to the development of novel therapeutic strategies for pain patients.

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

scholarly journals Noncoding RNAs

2014 ◽  
Vol 121 (2) ◽  
pp. 409-417 ◽  
Author(s):  
Brianna Marie Lutz ◽  
Alex Bekker ◽  
Yuan-Xiang Tao
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Antisense Rna ◽  
Dorsal Root ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Current Evidence ◽  
Noxious Stimuli ◽  
Chronic Pain Conditions ◽  
Novel Therapeutic Strategies

Abstract Chronic pain, a common clinical symptom, is often treated inadequately or ineffectively in part due to the incomplete understanding of molecular mechanisms that initiate and maintain this disorder. Newly identified noncoding RNAs govern gene expression. Recent studies have shown that peripheral noxious stimuli drive expressional changes in noncoding RNAs and that these changes are associated with pain hypersensitivity under chronic pain conditions. This review first presents current evidence for the peripheral inflammation/nerve injury–induced change in the expression of two types of noncoding RNAs, microRNAs, and Kcna2 antisense RNA, in pain-related regions, particularly in the dorsal root ganglion. The authors then discuss how peripheral noxious stimuli induce such changes. The authors finally explore potential mechanisms of how expressional changes in dorsal root ganglion microRNAs and Kcna2 antisense RNA contribute to the development and maintenance of chronic pain. An understanding of these mechanisms may propose novel therapeutic strategies for preventing and/or treating chronic pain.

scholarly journals Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines

2009 ◽  
Vol 05 (01) ◽  
pp. 40
Author(s):  
Adam Yagui-Beltrán ◽  
Lisa M Coussens ◽  
David M Jablons ◽  
◽  
◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Lung Carcinogenesis ◽  
Respiratory Homeostasis ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumorassociated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

Biologics in Children with Allergic Diseases

2020 ◽  
Vol 16 (2) ◽  
pp. 140-147
Author(s):  
Amelia Licari ◽  
Sara Manti ◽  
Alessia Marseglia ◽  
Maria De Filippo ◽  
Elisabetta De Sando ◽  
...  
Keyword(s):  
Allergic Diseases ◽  
Therapeutic Strategies ◽  
Pediatric Age ◽  
Biologic Therapies ◽  
Biological Drugs ◽  
Health Burden ◽  
Novel Therapeutic Strategies ◽  
Allergic Disorders ◽  
Novel Therapeutic

The prevalence of allergic diseases has been remarkably increased in the last decades. The global health burden of these conditions is substantial, since patients may experience disability, anxiety and emotional distress, social restrictions, and reduced quality of life and productivity, in particular, in the most severe cases. Recent advances in understanding the pathophysiology of allergic disorders have allowed identifying novel therapeutic strategies for the treatment of severe and uncontrolled allergic diseases. Although most studies have been performed in allergic asthma, biological drugs targeting other allergic diseases such as chronic spontaneous urticaria, atopic dermatitis, and food allergy are showing promising results. In this review, the most recent evidence on biologic therapies for allergic diseases, focusing on the pediatric age has been presented.

scholarly journals The Roles of Extracellular Vesicles in Malignant Melanoma

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2740
Author(s):  
Ying-Chen Cheng ◽  
Yu-An Chang ◽  
Yi-Jen Chen ◽  
Hsu-Min Sung ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Malignant Melanoma ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Bioactive Molecules ◽  
Different Types ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies

2021 ◽  
Vol 42 (03) ◽  
pp. 392-410
Author(s):  
Olawale Amubieya ◽  
Allison Ramsey ◽  
Ariss DerHovanessian ◽  
Gregory A. Fishbein ◽  
Joseph P. Lynch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Therapeutic Strategies ◽  
Term Survival ◽  
Chronic Lung Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Prevention And Treatment ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

AbstractThe primary factor that limits long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD continues to evolve. Consensus definitions of CLAD and the major CLAD phenotypes were recently updated and clarified, but it remains to be seen whether the current definitions will lead to advances in management or impact care. Understanding the potential differences in pathogenesis for each CLAD phenotype may lead to novel therapeutic strategies, including precision medicine. Recognition of CLAD risk factors may lead to earlier interventions to mitigate risk, or to avoid risk factors all together, to prevent the development of CLAD. Unfortunately, currently available therapies for CLAD are usually not effective. However, novel therapeutics aimed at both prevention and treatment are currently under investigation. We provide an overview of the updates to CLAD-related terminology, clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential strategies to treat and prevent CLAD.

Biologics in Children with Allergic Diseases

2020 ◽  
Vol 16 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Amelia Licari ◽  
Sara Manti ◽  
Alessia Marseglia ◽  
Maria De Filippo ◽  
Elisabetta De Sando ◽  
...  
Keyword(s):  
Allergic Diseases ◽  
Therapeutic Strategies ◽  
Pediatric Age ◽  
Biologic Therapies ◽  
Biological Drugs ◽  
Health Burden ◽  
Novel Therapeutic Strategies ◽  
Allergic Disorders ◽  
Novel Therapeutic

The prevalence of allergic diseases has been remarkably increased in the last decades. The global health burden of these conditions is substantial, since patients may experience disability, anxiety and emotional distress, social restrictions, and reduced quality of life and productivity, in particular, in the most severe cases. Recent advances in understanding the pathophysiology of allergic disorders have allowed identifying novel therapeutic strategies for the treatment of severe and uncontrolled allergic diseases. Although most studies have been performed in allergic asthma, biological drugs targeting other allergic diseases such as chronic spontaneous urticaria, atopic dermatitis, and food allergy are showing promising results. In this review, the most recent evidence on biologic therapies for allergic diseases, focusing on the pediatric age has been presented.

scholarly journals TCR-like antibodies in cancer immunotherapy

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Qinghua He ◽  
Zhaoyu Liu ◽  
Zhihua Liu ◽  
Yuxiong Lai ◽  
Xinke Zhou ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
T Cell Receptor ◽  
Molecular Mechanisms ◽  
Antibody Therapy ◽  
Cell Receptor ◽  
Therapeutic Strategies ◽  
Cell Surfaces ◽  
The Core ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Abstract Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.

scholarly journals The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents

2020 ◽  
Vol 21 (17) ◽  
pp. 6045 ◽  
Author(s):  
Filip Jovanovic ◽  
Kenneth D. Candido ◽  
Nebojsa Nick Knezevic
Keyword(s):  
Chronic Pain ◽  
Signaling Pathway ◽  
Peripheral Tissues ◽  
Chronic Pain Patients ◽  
The Central Nervous System ◽  
Chronic Pain Conditions ◽  
Pain Patients ◽  
Potential Use

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.

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