scholarly journals Rheumatic pain management: molecular aspects

2020 ◽  
Vol 14 (1) ◽  
pp. 93-100
Author(s):  
E. V. Chetina ◽  
E. P. Sharapova
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Pain Treatment ◽  
Inflammatory Diseases ◽  
Significant Proportion ◽  
Pharmacological Agents ◽  
Rheumatic Pain ◽  
Relieve Pain ◽  
Autoimmune Processes ◽  
Molecular Aspects

Rheumatic diseases (RDs), including osteoarthritis and rheumatoid arthritis, are non-infectious slowly progressive incurable inflammatory diseases that lead to prolonged disability due to damage to the musculoskeletal system. Pain is a dominant symptom at any stage of these diseases, is directly related to joint functioning, and determines the quality of life in patients. Moreover, despite the significant successes of studying the role of inflammation and regulation of autoimmune processes, the pathogenetic mechanisms for the development and maintenance of pain in RDs are little investigated. The nociceptive mechanisms due to inflammation and/or joint structural impairment are involved in the development of rheumatic pain. In addition, the latter is also associated with impaired signaling in the nervous system and with psychological problems in patients.At the present stage, pain treatment includes non-pharmacological interventions, as well as the use of certain pharmacological agents, in particular opioids and narcotic drugs. However, despite significant successes in the design of drugs that relieve pain, at present, a significant proportion of patients with RDs still experience pain after therapy. When designing novel drugs for the treatment of pain, it is necessary to take into account the molecular mechanisms of its development in RDs. This review considers the features of the manifestations of pain, its molecular markers and mechanisms at different stages of the disease in patients with the two most common RDs, such as rheumatoid arthritis and osteoarthritis. 

scholarly journals Molecular Aspects of Regional Pain Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Manuela Baronio ◽  
Hajra Sadia ◽  
Stefano Paolacci ◽  
Domenico Prestamburgo ◽  
Danilo Miotti ◽  
...  
Keyword(s):  
Skin Color ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Inflammatory Diseases ◽  
Treatment Options ◽  
Chronic Phase ◽  
Pain Syndrome ◽  
Promising Technique ◽  
Molecular Aspects ◽  
Trauma Stress

The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61–70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway.

Rheumatoid Arthritis: History, Stages, Epidemiology, Pathogenesis, Diagnosis and Treatment

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Abeer Fauzi Al-Rubaye ◽  
Mohanad Jawad Kadhim ◽  
Imad Hadi Hameed
Keyword(s):  
Rheumatoid Arthritis ◽  
Medicinal Plants ◽  
Systemic Disease ◽  
Modern Medicine ◽  
Whole Body ◽  
Internal Organs ◽  
Synthetic Drugs ◽  
Relieve Pain ◽  
Medicinal Treatment ◽  
Natural Drugs

The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs. Rheumatoid arthritis is chronic, progressive, disabling autoimmune disease characterized by systemic inflammation of joints, damaging cartilage and bone around the joints. It is a systemic disease which means that it can affect the whole body and internal organs such as lungs, heart and eyes. Although numbers of synthetic drugs are being used as standard treatment for rheumatoid arthritis but they have adverse effect that can compromise the therapeutic treatment. Unfortunately, there is still no effective known medicinal treatment that cures rheumatoid arthritis as the modern medicine can only treat the symptoms of this disease that means to relieve pain and inflammation of joints. It is possible to use the herbs and plants in various forms in order to relieve the pain and inflammation in the joints. There are so many medicinal plants that have shown anti rheumatoid arthritis properties. So the plants and plant product with significant advantages are used for the treatment of rheumatoid arthritis. The present review is focused on the medicinal plants having anti rheumatoid arthritis activity

EVALUATION OF THE EFECTS OF ELECTRONIC ACUPUNCTURE COMBINED WITH “TAM TY THANG” REMEDY IN THE TREATMENT OF RHEUMATOID ARTHRITIS BY WIND-COLD-DAMP

2017 ◽  
pp. 122-127
Author(s):  
Thi Luu Nguyen ◽  
Thi Tan Nguyen
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Prospective Study ◽  
Key Words Rheumatoid Arthritis ◽  
Good Effect ◽  
Good Level ◽  
Relieve Pain ◽  
Level Of Activity ◽  
Before And After ◽  
The Moment

Objectives: To assess the effect of electronic acupuncture combined with “Tam ty thang” remedy in the treatment of rheumatoid arthritis by wind-cold-damp. Materials and methods: prospective study, comparing before and after treatment, including 43 patients who were diagnosed with rheumatoid arthritis by wind-cold-damp according to traditional medicine. Results: good level occupied 69,8%, and fair good level occupied 30,2%.The improved motor function accounted for 95.3%, to relieve pain up to 95,3%, reducing inflammation of VSS in 1 hour at the moment No 31,65, N28 17,88. The improvement in the level of activity of the hand reached 48,8% for good level. Conclusions: The method of electronic acupuncture combined with “Tam ty thang” remedy have a good effect in the treatment of rheumatoid arthritis by wind-cold-damp and it didn’t cause significantly side effects in clinic. Key words: rheumatoid arthritis, electronic acupuncture, “Tam ty thang” remedy

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

scholarly journals Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Scott A. Scarneo ◽  
Liesl S. Eibschutz ◽  
Phillip J. Bendele ◽  
Kelly W. Yang ◽  
Juliane Totzke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Bone Formation ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Cartilage Damage ◽  
Cytokine Signaling ◽  
Periosteal Bone Formation ◽  
Bone Width

Abstract Objectives To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. Methods Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). Results Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Conclusion Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.

scholarly journals Molecular remission at T cell level in patients with rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Inamo ◽  
Katsuya Suzuki ◽  
Masaru Takeshita ◽  
Yasushi Kondo ◽  
Yuumi Okuzono ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Disease Control ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Principal Component ◽  
Cell Level ◽  
Molecular Remission ◽  
Signature Genes

AbstractWhile numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

scholarly journals Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology

2021 ◽  
Vol 22 (14) ◽  
pp. 7311
Author(s):  
Mateusz Wawro ◽  
Jakub Kochan ◽  
Weronika Sowinska ◽  
Aleksandra Solecka ◽  
Karolina Wawro ◽  
...  
Keyword(s):  
Family Member ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Psoriasis Patient ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Transcript Levels

The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts.

scholarly journals Expression and function of Smad7 in autoimmune and inflammatory diseases

2021 ◽  
Author(s):  
Yiping Hu ◽  
Juan He ◽  
Lianhua He ◽  
Bihua Xu ◽  
Qingwen Wang
Keyword(s):  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Signaling Mechanism ◽  
And Function

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.

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