scholarly journals THIOZOLIDINEDIONES IN THE TREATMENT OF PATIENTS WITH EXTENSIVE PSORIASIS AND CONCOMITANT ALIMENTARY OBESITY

2020 ◽  
Vol 20 (4) ◽  
pp. 30-34
Author(s):  
Ya.O. Yemchenko ◽  
K.Ye. Ishcheikin ◽  
I.P. Kaidashev
Keyword(s):  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Current Data ◽  
The Body ◽  
Internal Organs ◽  
Single View ◽  
Multifactorial Diseases ◽  
Alimentary Obesity ◽  
Inflammatory Processes

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, affected the skin, joints, internal organs and systems of the body. Despite the significant prevalence of psoriasis and a large number of studies devoted this problem there is still no single view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it seems to be reasonable to focus on the common comorbidities or multimorbidities, which may occur in the course of psoriasis, as this issue is still insufficiently studied. Recent reports have proven the evidences of indisputable link between psoriasis and obesity. The scientific literature extensively covers the issues of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and in particularly the role of proinflammatory nuclear transcription factors, thiazolidinediones have been found out as pathogenetically justified medicine of choice for the therapy of these diseases. In this study, we determined the effectiveness of using 30 mg of pioglitazone daily for 6 months in the course of treatment for patients with extensive psoriasis vulgaris of moderate severity, who were also diagnosed as having concomitant grade І-ІІ alimentary obesity that was supported by clinical and immunological findings evidenced of systemic inflammation. Analyzing the results obtained, we have found out the prolonged therapy with pioglitazone leads to a decrease in systemic inflammation and contributes to a milder recurrent course of psoriasis.

scholarly journals APPLICATION OF PIOGLITAZONE IN THE COMPREHENSIVE TREATMENT OF PSORIATIC PATIENTS WITH CONCOMITANT ALIMENTARY OBESITY

2020 ◽  
Vol 24 (5-6) ◽  
pp. 7-10
Author(s):  
Ya.O. Yemchenko ◽  
K.Ye. Ishcheikin ◽  
I.P. Kaidashev
Keyword(s):  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Pathological Process ◽  
Current Data ◽  
The Body ◽  
Comprehensive Treatment ◽  
Single View ◽  
Multifactorial Diseases ◽  
Alimentary Obesity

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, in which the skin, joints, internal organs and systems of the body are involved in the pathological process. Despite the significant prevalence of psoriasis and a large number of studies on this problem, there is still no single view on the pathogenesis of this dermatosis. To objectively understand the pathogenesis of psoriasis, it is necessary to take into account the insufficiently studied comorbidity of this pathology. Recently, an indisputable link between psoriasis and obesity has been proven. The scientific literature widely covers the issue of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and taking into account the role of proinflammatory nuclear transcription factors, thiazolidinediones are the pathogenetically justified drugs of choice for treatment of these diseases. In this study, we determined the effectiveness of using 15 mg of pioglitazone once a day for 6 months in the treatment of patients with extensive psoriasis vulgaris of moderate severity and concomitant grade І-ІІ alimentary obesity by clinical and immunological examination of systemic inflammation. Analyzing the results of the study, it was found that long-term use of pioglitazone, even in small doses, led to a decrease in systemic inflammation and contributed to a milder course of psoriasis in recurrence of the disease.

scholarly journals Glutathione S - transferases class Pi and Mi and their significance in oncology

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Zofia Marchewka ◽  
Agnieszka Piwowar ◽  
Sylwia Ruzik ◽  
Anna Długosz
Keyword(s):  
Redox Homeostasis ◽  
Current Data ◽  
Altered Expression ◽  
Potential Marker ◽  
Inflammatory Processes ◽  
Glutathione S Transferases ◽  
Endogenous Substrates ◽  
Cancer Tissues ◽  
Serum And Urine

In this article the current data, which shows that glutathione S-transferases (GST) class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi) in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

scholarly journals ROLE OF MACROPHAGES IN IMMUNOPATHOGENESIS OF PSORIASIS AND OBESITY

2018 ◽  
Vol 18 (4) ◽  
pp. 122-127 ◽  
Author(s):  
Ya. Yemchenko
Keyword(s):  
Weight Loss ◽  
Systemic Inflammation ◽  
Genetic Factor ◽  
Skin Diseases ◽  
Inflammatory Reactions ◽  
Multifactorial Diseases ◽  
Psoriatic Disease ◽  
Close Relationship ◽  
Unified View

Psoriasis is one of the most common chronic recurrent multifactorial diseases of the skin with a predominance of genetic factor. The disease is characterized by hyperproliferation of epidermal cells, impairment in the keratinisation process against inflammatory reactions in the dermis, and by lesions on the nails, joints and scalp. According to the results of clinical and epidemiological research, about 3-4% of the population of our planet has psoriasis, regardless of gender, age and ethnic group, while the share of this pathology in the overall structure of skin diseases reaches from 1% - to 40% [4, 5], according to various data. However, despite the widespread of psoriasis and the large number of works on this problem, there is still no unified view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it is necessary to take into account the insufficiently studied comorbidities typically associated with this pathology. Recently, there has been a tendency towards the growth of psoriatic disease and obesity in the pathogenesis of which a significant role is assigned to systemic inflammation and macrophages. According to the results of this research, it has been found out that obesity and psoriasis has a common link of the pathogenesis, systemic inflammation, which manifests itself in the increased number of macrophages producing a large number of proinflammatory cytokines. Thus, obesity and inflammation causes a vicious circle of cause-and-effect relationships. Obesity provokes inflammation, and inflammation, in turn, increases obesity and prevents weight loss. The close relationship between psoriasis and obesity is extremely important in selecting patient-centred therapy. Therefore, the goal of further research is to carry out detailed study of the psoriatic comorbidities that will contribute into revealing new targets for the treatment of this dermatosis.

scholarly journals Molecular mechanisms of control of differentiation of regulatory t-lymphocytes by exogenous melatonin

2019 ◽  
Vol 484 (2) ◽  
pp. 224-227
Author(s):  
N. S. Glebezdina ◽  
A. A. Olina ◽  
I. V. Nekrasova ◽  
E. M. Kuklina
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
The Body ◽  
Membrane Receptors ◽  
Cell Subpopulation ◽  
Exogenous Melatonin ◽  
Regulatory T Lymphocytes ◽  
Treg Differentiation

We investigated the role of epiphyseal hormone melatonin in the differentiation of naive CD4+T cells into regulatory T cells (Treg). The hormone at physiological and pharmacological concentrations inhibited Treg differentiation, decreasing both the proportion of CD4+FOXP3+ cells in the culture and the level of TGF‑β, the key cytokine for this T cell subpopulation. The inhibitory effect of exogenous melatonin was due to its interaction with the membrane receptors MT1 and MT2. At the same time, the signals realized through RORa — the nuclear receptor for melatonin — stimulated Treg formation; however, they were considerably weaker than the signals from the membrane receptors and were overlapped by the latter. Since the Treg subpopulation plays an important role in physiological and pathological processes in the body, the revealed effects of melatonin should be taken into account in its therapeutic use.

scholarly journals Cellular Responses to Proteasome Inhibition: Molecular Mechanisms and Beyond

2019 ◽  
Vol 20 (14) ◽  
pp. 3379 ◽  
Author(s):  
Nicolas Albornoz ◽  
Hianara Bustamante ◽  
Andrea Soza ◽  
Patricia Burgos
Keyword(s):  
Side Effects ◽  
Inclusion Bodies ◽  
Molecular Mechanisms ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Cellular Responses ◽  
Cell Responses ◽  
Different Types ◽  
Inflammatory Processes

Proteasome inhibitors have been actively tested as potential anticancer drugs and in the treatment of inflammatory and autoimmune diseases. Unfortunately, cells adapt to survive in the presence of proteasome inhibitors activating a variety of cell responses that explain why these therapies have not fulfilled their expected results. In addition, all proteasome inhibitors tested and approved by the FDA have caused a variety of side effects in humans. Here, we describe the different types of proteasome complexes found within cells and the variety of regulators proteins that can modulate their activities, including those that are upregulated in the context of inflammatory processes. We also summarize the adaptive cellular responses activated during proteasome inhibition with special emphasis on the activation of the Autophagic-Lysosomal Pathway (ALP), proteaphagy, p62/SQSTM1 enriched-inclusion bodies, and proteasome biogenesis dependent on Nrf1 and Nrf2 transcription factors. Moreover, we discuss the role of IRE1 and PERK sensors in ALP activation during ER stress and the involvement of two deubiquitinases, Rpn11 and USP14, in these processes. Finally, we discuss the aspects that should be currently considered in the development of novel strategies that use proteasome activity as a therapeutic target for the treatment of human diseases.

scholarly journals THE ROLE OF INTERLEUKIN-6 SIGNALING IN DEVELOPMENT OF SYSTEMIC INFLAMMATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

2018 ◽  
Vol 1 (69) ◽  
pp. 97-106 ◽  
Author(s):  
Татьяна Виткина ◽  
Tatyana Vitkina ◽  
К Сидлецкая ◽  
K Sidleckaya
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Systemic Inflammation ◽  
Interleukin 6 ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Damage Initiation

The review focuses on the role of interleukin-6 (IL-6) signaling in the development of a systemic inflammatory process in chronic obstructive pulmonary disease (COPD). In most researches the attention is paid to local inflammation in COPD. However, it is known that the pathology is characterized by a systemic inflammatory process, which is manifested in the increased levels of proinflammatory mediators in blood flow, and the study of the molecular mechanisms of its development is very important for the therapy of the disease. One of the key mediators of systemic inflammation is cytokine IL-6 which has pro- and antiinflammatory properties. Its effect on the cells is determined by the type of signaling. Nowadays three types of IL-6 signaling are identified: transsignaling, classical and cluster signaling. The review presents the known pathophysiological mechanisms of the development of systemic inflammation in COPD involving IL-6. As a proinflammatory cytokine, IL-6 performs the following functions: transmission of a signal on lung tissue damage, initiation of leukocyte migration into the inflammation site, inhibition of T-cell apoptosis into the inflammation site, influence on T helper differentiation, participation in pathophysiological reactions of development of emphysema and fibrosis. The significance of IL-6 transsignaling for the development of inflammation in COPD has been confirmed by many studies, while there are practically no works devoted to the study of classical IL-6 signaling in COPD. The data presented in the review indicate the need for further study of the role of different types of IL-6 signaling, especially classical signaling, in the regulation of systemic inflammation in COPD.

scholarly journals Potential therapeutic manipulations of the CXCR3 chemokine axis for the treatment of inflammatory fibrosing diseases

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1197
Author(s):  
Morgan K. Groover ◽  
Jillian M. Richmond
Keyword(s):  
Wound Healing ◽  
Tumor Metastasis ◽  
Ex Vivo ◽  
Experimental Models ◽  
The Body ◽  
Human Tissues ◽  
Inflammatory Processes ◽  
Opinion Article ◽  
Different Tissues

Chemokines play important roles in homeostasis and inflammatory processes. While their roles in leukocyte recruitment are well-appreciated, chemokines play additional roles in the body, including mediating or regulating angiogenesis, tumor metastasis and wound healing. In this opinion article, we focus on the role of CXCR3 and its ligands in fibrotic processes. We emphasize differences of the effects of each ligand, CXCL9, CXCL10 and CXCL11, on fibroblasts in different tissues of the body. We include discussions of differences in signaling pathways that may account for protective or pro-fibrotic effects of each ligand in different experimental models and ex vivo analysis of human tissues. Our goal is to highlight potential reasons why there are disparate findings in different models, and to suggest ways in which this chemokine axis could be manipulated for the treatment of fibrosis.

scholarly journals Type 3 Innate Lymphoid Cells as Regulators of the Host-Pathogen Interaction

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Valle-Noguera ◽  
Anne Ochoa-Ramos ◽  
Maria José Gomez-Sánchez ◽  
Aranzazu Cruz-Adalia
Keyword(s):  
Transgenic Mice ◽  
Molecular Mechanisms ◽  
Specific Activity ◽  
Innate Lymphoid Cells ◽  
The Body ◽  
Lymphoid Cells ◽  
Intracellular Pathogens ◽  
Host Pathogen Interaction ◽  
Type 3

Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals Peripheral Mechanisms of Dental Pain: The Role of Substance P

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Paola Sacerdote ◽  
Luca Levrini
Keyword(s):  
Substance P ◽  
Molecular Mechanisms ◽  
Dental Pain ◽  
Therapeutic Strategies ◽  
Current Evidence ◽  
Trigeminal Ganglia ◽  
Clinical Observations ◽  
P Concentration ◽  
Inflammatory Processes

Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

Sign in / Sign up

Export Citation Format

Share Document