scholarly journals The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

2021 ◽  
Vol 22 (23) ◽  
pp. 12793
Author(s):  
Rohan Singh ◽  
Sindhuja Koppu ◽  
Patrick O. Perche ◽  
Steven R. Feldman

Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.


2020 ◽  
Vol 16 (6) ◽  
pp. 860-865
Author(s):  
Sedigheh Tavakoli-Dastjerdi ◽  
Mandana Tavakkoli-Kakhki ◽  
Ali R. Derakhshan ◽  
Azam Teimouri ◽  
Malihe Motavasselian

Background: Anal fissure (AF) is a common disease associated with severe pain and reduced quality of life. Factors related to lifestyle, including diet and bowel habits, play a pivotal role in its pathogenesis. Most of the chronic fissures are not responsive to drugs and more likely to recur. Given the significance of diet in Persian medicine (PM), investigation on physiopathology and appropriate foods can be useful for decreases in AF symptoms and consequences. Objective: This study was intended to evaluate the role of diet in the formation and progression of AF from the perspective of PM. Methods: In this study, the most important resources of PM dating back to thousands of years were reviewed. All these textbooks contained a section on AF, its causes, and treatment. Further analysis was performed on these resources in comparison with databank and resources of modern medicine to develop a food-based strategy for AF management. Results: From the view of PM, the warmth and dryness of anus temperament accounted for AF. Both Persian and modern medicine identified constipation as another cause for AF. Therefore, avoidance from some foods and commercial baked goods was recommended. Both Persian and modern medicine forbad the following foods: potato, cabbage, cauliflower, pasta, beef, fish, and so forth. High fiber and oligo-antigen diets with some limitations have garnered more attention. Conclusion: An integrative approach is recommended employing both Persian and modern medicine for AF. There have been some evidence in this regard, however standardized clinical trials are required for future research.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Marcin Sochal ◽  
Piotr Bialasiewicz ◽  
Agata Gabryelska ◽  
Renata Talar-Wojnarowska ◽  
Jakub Fichna ◽  
...  

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.


2018 ◽  
Vol 08 (01) ◽  
pp. e50-e54
Author(s):  
Vitchayaporn Saengow ◽  
Sirikarn Tangcheewinsirikul

Introduction Migraine is the most common primary headache in children which leads to disturbance of school performance and impaired quality of life. The prevalence of migraine is different between countries and ethnicities; this study determines the prevalence and precipitating factors of migraine in Thailand. Method This cross-sectional school-based study was conducted in Nakhon Ratchasima. The children aged between 12 and 18 years from four secondary schools were selected by stratified randomization method. The screening questionnaire and directed interview with physical examination were done and migraine was diagnosed based on the criteria of International Classification of Headache Disorders III. The prevalence of migraine was identified and baseline characteristic of disease with precipitating factors was evaluated. Results A total of 2,744 students aged between 12 and 18 years (900 males, 1,844 females) were recruited; mean age was 14.3 ± 1.75 years. Fifty-five students were diagnosed with migraine (20 males [36.36%], 35 females [63.64%], mean age: 15.1 ± 1.6 years). The prevalence of migraine was 1.98%. Migraine prevalence was predominant in female adolescents with a common feature being migraine without aura. The important precipitating factor in this study was stress from academic achievement. Conclusion Migraine is a common disease in children and under-recognized in school students, and stress is the major precipitating factor.


Author(s):  
Viktor Dmytryk ◽  
Tetiana Luhovska ◽  
Pavel Yakovlev ◽  
Olexiy Savchuk ◽  
Ludmila Ostapchenko ◽  
...  

Bladder Cancer (BC) is a common disease worldwide. Chronic inflammation is one of the key mechanisms for the development of BC. This study enrolled 40 patients. Preoperative plasma levels of IL-1β, IL-4, IL-6, IL-10, IL-12β, TNF-α and IFN-γ were determined by ELISA. In our study, we observed diverse changes in the levels of cytokines in patients with BC Stage I, II, III and IV. The levels of IL-1β was increased for stage I, stage II, and stage III. The level of TNF-α was increased for stage II, stage III, stage IV. The levels of IL-4, IL-6, IL-10 and IL-12β were increased in patients with stage III and IV only. The levels of IFN- γ declined for stage II, stage III and stage IV with the lowest levels in patients with Stage IV. In our study, we investigated alteration in levels of Th-1 and Th-2-like cytokine profile, but some deficiency in Th1- status discovered in patients with BC.


2013 ◽  
Vol 61 (2) ◽  
pp. 209-219 ◽  
Author(s):  
Janko Mrkun ◽  
Marjan Kosec ◽  
Petra Zrimšek

The aim of this study was to address the question whether changes in boar semen quality after short-term storage could be predicted on the basis of standard semen parameters and TNF-α level determined on the day of semen collection under commercial conditions. Progressive motility showed the highest positive correlation with morphology on day 0 of collection, and progressive motility on day 3 (P < 0.05) showed a negative correlation with acrosome abnormalities (P < 0.05). According to the area under receiver operating characteristics (ROC) curves (AUCs), progressive motility could also be used in predicting semen quality after 3 days of storage (AUC > 0.5; P < 0.05). TNF-α in seminal plasma is the only parameter measured on day 0 to show a significant correlation with the percentage of viable spermatozoa after 3 days of semen storage (r = 0.495, P < 0.05). ROC analysis shows that TNF-α level is helpful in discriminating viability outcome after semen storage (AUC = 0.94, P < 0.001). We can predict with 92.35% certainty that fresh semen samples with more than 150 pg/ml of TNF-α in the seminal plasma will retain more than 85% of viable spermatozoa after 3 days of storage. Thus, TNF-α can contribute to predicting the quality of short-term stored semen.


2018 ◽  
Vol 34 (5) ◽  
pp. 498-506 ◽  
Author(s):  
Olina Efthymiadou ◽  
Jean Mossman ◽  
Panos Kanavos

Objectives:Health-related quality of life (HRQoL) data generated by generic, preference-based instruments (i.e., EQ-5D) are highly demanded in health policy decision making, because they allow for direct comparisons of HRQoL outcomes between disease areas. We aimed to quantify HRQoL outcomes in breast cancer (BC), rheumatoid arthritis (RA), multiple sclerosis (MS), rare cancers (RC), and rare disease (RD) patients and understand the patterns that differentiate HRQoL outcomes between these disease areas, and more specifically between rare and more common disease population groups.Methods:An international, Web survey of patients measured HRQoL (EQ-5D-5L), self-perceived health (EQ-5D-5L Visual Analogue Scale), and additional QoL dimensions, such as patient disability level.Results:We received 675 completed responses. Average utility loss was 53.5 percent, 32.5 percent, and 33.3 percent for RD, RA, and MS patients, respectively, in contrast to 18.6 percent for BC and RC patients. Statistically significant differences (p < .05) were observed between disease groups in all EQ-5D-5L domain outcomes, apart from that of “Anxiety/Depression.” Severe and/or extreme problems were reported in performing usual activities for RD and RC (34 percent and 13 percent of overall problems reported respectively), mobility for MS (18 percent), pain/discomfort for RA (13 percent), and anxiety/depression for BC (7 percent) patients.Conclusions:We demonstrated significant differences in the dimensions that drive HRQoL outcomes between rare and more common diseases and showcased that the same EQ-5D utility may reflect very different severities depending on the patient population under investigation. Future research should examine whether outcomes in other, critical HRQoL domains not included in generic measures also highlight significant differences across disease areas.


Author(s):  
Margaret S. Herridge ◽  
Jane Batt

Critical illness is an important life event with a lasting legacy. Patients acquire new nerve, brain, and muscle injury, and sustain important functional dependencies that have clear consequences for subsequent health-related quality of life. Intensive care unit (ICU)-acquired weakness is a prevalent and likely ubiquitous consequence of severe illness. Patients degrade their skeletal muscle within hours of ICU admission through upregulation of different proteolytic pathways, regardless of the inciting aetiology. This may support an approach to muscle injury, sustained disability and subsequent approach to rehabilitation that is aetiologically neutral, and linked to molecular pathophysiology and associated functional outcome. The physical devastation of critical illness affects the entire family unit and family caregivers need to be acknowledged as important risk modifiers for outcome and have their needs addressed as part of an interprofessional rehabilitation intervention.


Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1144 ◽  
Author(s):  
Alexandra J Malbon ◽  
Sonja Fonfara ◽  
Marina L Meli ◽  
Shelley Hahn ◽  
Herman Egberink ◽  
...  

Feline infectious peritonitis (FIP) is a fatal immune-mediated disease of cats, induced by feline coronavirus (FCoV). A combination of as yet poorly understood host and viral factors combine to cause a minority of FCoV-infected cats to develop FIP. Clinicopathological features include fever, vasculitis, and serositis, with or without effusions; all of which indicate a pro-inflammatory state with cytokine release. As a result, primary immune organs, as well as circulating leukocytes, have thus far been of most interest in previous studies to determine the likely sources of these cytokines. Results have suggested that these tissues alone may not be sufficient to induce the observed inflammation. The current study therefore focussed on the liver and heart, organs with a demonstrated ability to produce cytokines and therefore with huge potential to exacerbate inflammatory processes. The IL-12:IL-10 ratio, a marker of the immune system’s inflammatory balance, was skewed towards the pro-inflammatory IL-12 in the liver of cats with FIP. Both organs were found to upregulate mRNA expression of the inflammatory triad of cytokines IL-1β, IL-6, and TNF-α in FIP. This amplifying step may be one of the missing links in the pathogenesis of this enigmatic disease.


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