Persistent Inflammatory State Research Articles

Insights and Interventions in Age-Associated Inflammation.

Aging is a systemic, complex, and heterogeneous process characterized by a progressive decline in physiological functions, rendering it a major risk factor for various chronic diseases. Chronic inflammation has emerged as both a hallmark and a driver in this complicated process. This persistent inflammatory state arises from a spectrum of stimuli, ranging from external pathogens to internal cellular remnants, to metabolic dysregulation, and to chronic stress. Here, we examine recent mechanistic advances into the driving forces behind age-related chronic inflammation, explore promising anti-inflammatory strategies to mitigate aging, and address current challenges, proposing future directions to propel this evolving field toward translational breakthrough.

Neuroprotective Effects of Dexamethasone in a Neuromelanin-Driven Parkinson’s Disease Model

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra that primarily affects movement control. Neuroinflammation plays a pivotal role in driving the disease’s progression. The persistent inflammatory state in the brain exacerbates neuronal damage, creating a cycle that perpetuates the neurodegenerative process. Glucocorticoids, such as dexamethasone, have potent anti-inflammatory properties and have been studied for their neuroprotective potential in different neurodegenerative diseases. However, their specific impact on PD remains unclear. This study aimed to evaluate the impact of dexamethasone on a neuromelanin (NM)-driven model of PD. We demonstrated that dexamethasone administration significantly improved motor function and preserved dopaminergic neuron compared to untreated controls in our study. These neuroprotective effects were mediated, at least in part, by suppressing reactive microglia and reducing the infiltration of peripheral immune cells into the brain. Our findings underscore the potential therapeutic benefits of dexamethasone in mitigating neuroinflammation and maintaining neuronal integrity in a NM-driven model of PD. These results advocate for further investigation into glucocorticoid-based therapies as adjunctive treatments for PD, particularly in scenarios where neuroinflammation contributes prominently to disease progression.

Photobiomodulation studies on diabetic wound healing: An insight into the inflammatory pathway in diabetic wound healing.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Metabolic and Inflammatory Aspects of Iron Deficiency in Obese

Obesity is a chronic disease with a complex etiology, characterized by a persistent inflammatory state induced by various pro-inflammatory cytokines, including interleukin-6. This condition leads to increased production of hepcidin, a protein hormone responsible for regulating iron homeostasis. Hepcidin's primary function is to inhibit iron absorption by enterocytes, the cells lining the small intestine. Symptoms of iron deficiency, which is crucial for oxygen transport, energy production, and immune system support, can be varied and often nonspecific, such as general weakness, pallor, or concentration difficulties, potentially prolonging the diagnostic process. This article aims to analyze the relationship between obesity and iron deficiency in the metabolic context. Obesity, being one of the most prevalent health issues of the modern world, is associated with numerous complications, including disturbances in iron metabolism. Iron deficiency in obese individuals can lead to anemia, reduced physical performance, and cognitive impairments. Traditional treatment methods for this micronutrient deficiency involve supplementation. However, supplementation shows reduced efficacy in overweight and obese individuals, likely due to elevated hepcidin levels. A more effective approach should include interventions targeting not only the supplementation of the missing micronutrient but also weight reduction.

The Association between IL-1β and IL-18 Levels, Gut Barrier Disruption, and Monocyte Activation during Chronic Simian Immunodeficiency Virus Infection and Long-Term Suppressive Antiretroviral Therapy.

HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of Human Immunodeficiency Virus (HIV) infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption (IEBD). Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for IEBD biomarkers, inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). During the chronic phase of treated SIV infection, elevated levels of plasma IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP). Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10 and 12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV + ART phase along with a trend of increase in the frequencies of activated CD14+CD16+ intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could fuel metabolic syndrome. Further research is needed to understand the mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated metabolic complications, enabling targeted interventions in people with HIV.

From Modic to Disc Endplate Bone Marrow Complex - The Natural Course and Clinical Implication of Vertebral Endplate Changes.

Review article. A review of literature on the epidemiology, natural course, pathobiology and clinical implications of vertebral endplate changes. A literature search was performed using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the last 10 years were analysed. The searches were performed using Medical Subject Headings terms, and the subheadings used were "Vertebral endplate changes", "Modic changes", "Disc Endplate Bone Marrow complex". The disc, endplate (EP), and bone marrow region of the spine constitute a unified morphological and functional unit, with isolated degeneration of any one structure being uncommon. Disc degeneration causes endplate defects, which result in direct communication and a constant cross-talk between the disc and the vertebral body. This may result in a persistent inflammatory state of the vertebral bone marrow, serving as a major pain generator. This review article focuses on vertebral endplate changes and how the current understanding has progressed from the Modic classification to the Disc Endplate Bone Marrow complex classification. It provides a clear portrayal of the natural course of these alterations and their clinical implications in low back pain. In light of the heightened interest and current prominence of vertebral endplate changes within the spine community, we must progress beyond the Modic changes to achieve a comprehensive understanding. The DEBM complex classification will play a major part in disc degeneration research and clinical care, representing a considerable advancement in our understanding of the vertebral endplate changes over the classical Modic changes.

Research Progress of Pyroptosis in Diabetic Kidney Disease.

Pyroptosis, known as one typical mode of programmed cell death, is generally characterized by the cleaved gasdermin family (GSDMs) forming pores in the cell membrane and inducing cell rupture, and the activation of aspartate-specific proteases (caspases) has also been found during this process. Diabetic Kidney Disease (DKD) is caused by the complication of diabetes in the kidney, and the most important kidney's function, Glomerular Filtration Rate (GFR), happens to drop to less than 90% of its usual and even lead to kidney failure in severe cases. The persistent inflammatory state induced by high blood glucose implies the key pathology of DKD, and growing evidence shows that pyroptosis serves as a significant contributor to this chronic immune-mediated inflammatory disorder. Currently, the expanded discovery of GSDMs, pyroptosis, and its association with innate immunity has been more attractive, and overwhelming research is needed to sort out the implication of pyroptosis in DKD pathology. In this review, we comb both classical studies and newly founds on pyroptosis, prick off the novel awakening of pyroptosis in DKD, and center on the significance of pyroptosis in DKD treatment, aiming to provide new research targets and treatment strategies on DKD.

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy.

HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of HIV infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption and CVD pathogenesis. Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for biomarkers of intestinal epithelial barrier disruption (IEBD), inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). Higher plasma levels of IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP), during the chronic phase of treated SIV infection. Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10-12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV+ART phase along with a trend of increase in frequencies of activated CD14 + CD16 + intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could accelerate CVD pathogenesis. Further research is needed to understand mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated CVD and metabolic complications, enabling targeted interventions in people with HIV.

CGAS-STING signaling in cardiovascular diseases.

Sterile inflammation, characterized by a persistent chronic inflammatory state, significantly contributes to the progression of various diseases such as autoimmune, metabolic, neurodegenerative, and cardiovascular disorders. Recent evidence has increasingly highlighted the intricate connection between inflammatory responses and cardiovascular diseases, underscoring the pivotal role of the Stimulator of Interferon Genes (STING). STING is crucial for the secretion of type I interferon (IFN) and proinflammatory cytokines in response to cytosolic nucleic acids, playing a vital role in the innate immune system. Specifically, research has underscored the STING pathway involvement in unregulated inflammations, where its aberrant activation leads to a surge in inflammatory events, enhanced IFN I responses, and cell death. The primary pathway triggering STING activation is the cyclic GMP-AMP synthase (cGAS) pathway. This review delves into recent findings on STING and the cGAS-STING pathways, focusing on their regulatory mechanisms and impact on cardiovascular diseases. It also discusses the latest advancements in identifying antagonists targeting cGAS and STING, and concludes by assessing the potential of cGAS or STING inhibitors as treatments for cardiovascular diseases.

Association Between `Life's Essential 8’ and Periodontitis: A Cross-Sectional Study From the NHANES Database

BackgroundPeriodontitis as a chronic inflammatory disease, and its persistent inflammatory state can lead to the cardiovascular system damage. Studies have shown that life's essential 8 (LE8), as an indicator of cardiovascular health, was associated with the risk of several inflammatory diseases. This study aimed to assess the association between LE8 and its subscales and the risk of periodontitis. MethodsData of participants who accepted the periodontitis examinations were extracted from the National Health and Nutrition Examination Surveys (NHANES) database (2009-2014). LE8 contains four health behaviors (diet, physical activity, nicotine exposure, sleep health) and four health factors (BMI, blood lipids, blood glucose and blood pressure) and was categorized into low (0-49), moderate (50-79), and high (80-100) level. Covariates included demographic information, laboratory values, diseases history and medications history. The weighted univariate and multivariate logistic regression models were performed to assess the association between LE8 and periodontitis, with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender and cardiovascular disease (CVD) history were further assessed the association. ResultsTotal 5,106 adults were included, of whom 2,606 (51.04%) had periodontitis. After adjustment for age, gender, race, PIR, education level, marital status, drinking, CVD, nonsteroidal anti-inflammatory agents, waist circumference (WC), vitamin D (VD) and dental floss/device, high LE8 score (OR=0.48, 95%CI: 0.32-0.73), higher health behaviors score (OR=0.56, 95%CI: 0.42-0.73) and higher health factors score (OR=0.71, 95%CI: 0.51-0.99) were associated with the lower occurrence of periodontitis, especially in adults with male, aged <60 years and without CVD history. Moreover, the occurrence of periodontitis was decreased when score of total LE8, health factors and health behaviors increased every 10 scores. ConclusionLE8 score and its subscales scores were associated with the lower odds of periodontitis. Promoting adherence to high cardiovascular health levels may be beneficial to reduce the burden of periodontitis.

Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity.

The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging. This chronic inflammatory state, also known as inflammaging, induced by the chronic activation of the innate immune system via the macrophage, is controlled by the gut microbiota, which links nutrition, metabolism, and the innate immune response. Here, we present the functional roles of prebiotics, probiotics, synbiotics, and postbiotics as bioactive compounds by underscoring their putative contributions to (1) the reduction in gut hyperpermeability due to lipopolysaccharide (LPS) inactivation, (2) increased intestinal barrier function as a consequence of the upregulation of tight junction proteins, and (3) inhibition of proinflammatory pathways, overall leading to the alleviation of chronic inflammation in the management of obesity.

Atrial Fibrillation and Adipokines: A Pathophysiological Perspective

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria. Adipokines are bioactive molecules that are secreted by adipose tissue, and exert diverse effects on health and disease. Obesity is a complex condition influenced by multiple interconnected factors, and the specific mechanisms linking obesity to AF may vary among individuals. Obesity contributes to the development of atrial arrhythmia. Moreover, obesity plays major roles in the pathophysiology of AF and its associated complications by inducing systemic changes, including altered hemodynamics, heightened sympathetic tone, and a persistent low-grade inflammatory state. Although the associations between overweight or obesity and elevated risk of AF have been established, the underlying mechanisms remain incompletely characterized. This article highlights the pathophysiological aspects of adipokines, such as Angiopoietin-like protein 2, Fibroblast growth factor 21, Lipocalin, Vaspin, Visfatin, and Nesfatin-1, in AF and concludes that adipokines play major roles in AF pathogenesis.

Psoriasis as a Risk Factor for Skin Cancer: An International, Propensity-Matched Retrospective Cohort Study

Psoriasis, a chronic immune-mediated skin disorder impacting millions globally, is increasingly recognized for its links to various disease processes. As our understanding of immune dysregulation in psoriasis progresses, acknowledging the pivotal role of dysregulated T-cells in the pathogenic development of the persistent inflammatory state becomes crucial. This immune dysregulation and the resulting prevalent inflammatory state have raised concerns about psoriasis potentially serving as a significant comorbidity in cancer development among patients. To contribute to this discussion, we conducted a global retrospective cohort study with propensity score matching (PSM) using the TriNetX Analytics platform. The study aimed to investigate whether patients diagnosed with psoriasis face an elevated risk in the development of cutaneous malignancies, encompassing both melanoma and non-melanoma skin cancers. Our findings confirmed a noteworthy concern, revealing a significantly increased risk of developing cutaneous neoplasms in individuals with psoriasis. In conclusion, our study underscores the importance of heightened awareness and the necessity for routine skin cancer screenings in this unique patient population. The observed association between psoriasis and an increased risk of cutaneous neoplasms highlights the need for proactive medical interventions and emphasizes the potential impact of psoriasis as a comorbidity in the context of cancer development.

Intravenous Injection of PEI-Decorated Iron Oxide Nanoparticles Impacts NF-kappaB Protein Expression in Immunologically Stressed Mice.

Nanoparticle-based formulations are considered valuable tools for diagnostic and treatment purposes. The surface decoration of nanoparticles with polyethyleneimine (PEI) is often used to enhance their targeting and functional properties. Here, we aimed at addressing the long-term fate in vivo and the potential "off-target" effects of PEI decorated iron oxide nanoparticles (PEI-MNPs) in individuals with low-grade and persistent systemic inflammation. For this purpose, we synthesized PEI-MNPs (core-shell method, PEI coating under high pressure homogenization). Further on, we induced a low-grade and persistent inflammation in mice through regular subcutaneous injection of pathogen-associated molecular patterns (PAMPs, from zymosan). PEI-MNPs were injected intravenously. Up to 7 weeks thereafter, the blood parameters were determined via automated fluorescence flow cytometry, animals were euthanized, and the organs analyzed for iron contents (atomic absorption spectrometry) and for expression of NF-κB associated proteins (p65, IκBα, p105/50, p100/52, COX-2, Bcl-2, SDS-PAGE and Western blotting). We observed that the PEI-MNPs had a diameter of 136 nm and a zeta-potential 56.9 mV. After injection in mice, the blood parameters were modified and the iron levels were increased in different organs. Moreover, the liver of animals showed an increased protein expression of canonical NF-κB signaling pathway members early after PEI-MNP application, whereas at the later post-observation time, members of the non-canonical signaling pathway were prominent. We conclude that the synergistic effect between PEI-MNPs and the low-grade and persistent inflammatory state is mainly due to the hepatocytes sensing infection (PAMPs), to immune responses resulting from the intracellular metabolism of the uptaken PEI-MNPs, or to hepatocyte and immune cell communications. Therefore, we suggest a careful assessment of the safety and toxicity of PEI-MNP-based carriers for gene therapy, chemotherapy, and other medical applications not only in healthy individuals but also in those suffering from chronic inflammation.

Neutrophils' Contribution to Periodontitis and Periodontitis-Associated Cardiovascular Diseases.

Neutrophils represent the primary defense against microbial threats playing a pivotal role in maintaining tissue homeostasis. This review examines the multifaceted involvement of neutrophils in periodontitis, a chronic inflammatory condition affecting the supporting structures of teeth summarizing the contribution of neutrophil dysfunction in periodontitis and periodontal-related comorbidities. Periodontitis, a pathological condition promoted by dysbiosis of the oral microbiota, is characterized by the chronic inflammation of the gingiva and subsequent tissue destruction. Neutrophils are among the first immune cells recruited to the site of infection, releasing antimicrobial peptides, enzymes, and reactive oxygen species to eliminate pathogens. The persistent inflammatory state in periodontitis can lead to aberrant neutrophil activation and a sustained release of proinflammatory mediators, finally resulting in tissue damage, bone resorption, and disease progression. Growing evidence now points to the correlation between periodontitis and systemic comorbidities. Indeed, the release of inflammatory mediators, immune complexes, and oxidative stress by neutrophils, bridge the gap between local and systemic immunity, thus highlighting neutrophils as key players in linking periodontal inflammation to chronic conditions, including cardiovascular diseases, diabetes mellitus, and rheumatoid arthritis. This review underscores the crucial role of neutrophils in the pathogenesis of periodontitis and the complex link between neutrophil dysfunction, local inflammation, and systemic comorbidities. A comprehensive understanding of neutrophil contribution to periodontitis development and their impact on periodontal comorbidities holds significant implications for the management of oral health. Furthermore, it highlights the need for the development of novel approaches aimed at limiting the persistent recruitment and activation of neutrophils, also reducing the impact of periodontal inflammation on broader health contexts, offering promising avenues for improved disease management and patient care.

High Levels of IL-1β, TNF-α and MIP-1α One Month after the Onset of the Acute SARS-CoV-2 Infection, Predictors of Post COVID-19 in Hospitalized Patients.

The pandemic caused by SARS-CoV-2 infection has left behind a new symptomatology called post COVID-19, or "long COVID". The pathophysiological mechanisms still remain controversial; however, a link between persistent inflammation and these sequelae has been suggested. Herein, we longitudinally assessed up- and downstream molecules of the NLRP3 inflammasome's pathway in three study groups: healthy donors (HC, n = 14) and donors with a confirmed SARS-CoV-2 infection who had been hospitalized, the latter divided into post COVID-19 (PC, n = 27) and non-post COVID-19 patients (nPC, n = 27) based on the presence or absence of symptomatology at month 6, respectively. Plasma cytokines (IL-1β, IL-3, IL-6, IL-8, IL-18, IP-10, MIG, TNF-α, IFN-γ, MIP-1α and MIP-1β) and total peroxide (TPX) levels were quantified at baseline and at months 1 and 6 after the onset of the infection. Baseline values were the highest for both TPX and cytokines that progressively decreased thereafter the acute infection. IL-1β, MIP-1α and TNF-α at month 1 were the only cytokines that showed a significant difference between nPC and PC. These findings suggest that a persistent inflammatory state one month after the onset of SARS-CoV-2 infection related to specific cytokines (IL-1β, MIP-1α, and TNF-α) might guide to predicting post COVID-19 symptomatology.

AMPK activators suppress cholesterol accumulation in macrophages via suppression of the mTOR pathway

Atherosclerosis is a persistent inflammatory state that contributes significantly to cardiovascular disease, a primary cause of mortality worldwide. Enhanced lipid uptake by macrophages and their transformation into foam cells play a key role in the development of atherosclerosis. Recent studies using in vivo mouse models indicated that activation of AMPK has anti-atherosclerotic effects by upregulating the expression of cholesterol efflux transporters in foam cells and promoting cholesterol efflux. However, the pathway downstream of AMPK that contributes to elevated expression of cholesterol efflux transporters remains unclear. In this study, we found that activation of AMPK by AICAR and metformin inhibits foam cell formation via suppression of mTOR in macrophages. Specifically, activation of AMPK indirectly reduced the phosphorylation level of mTOR at Ser2448 and promoted the expression of cholesterol efflux transporters and cholesterol efflux. These inhibitory effects on foam cell formation were counteracted by mTOR activators. Metformin, a more nonspecific AMPK activator than AICAR, appears to inhibit foam cell formation via anti-inflammatory effects in addition to suppression of the mTOR pathway. The results of this study suggest that the development of new drugs targeting AMPK activation and mTOR inhibition may lead to beneficial results in the prevention and treatment of atherosclerosis.

New Insights into Pathogenesis, Diagnosis and Treatment of Psoriatic Arthritis

Introduction: Psoriatic Arthritis (PSA) is an inflammatory musculoskeletal disorder characterized by significant dysfunction in synovial tissue, tendons and axial sites. PSA is associated with metabolic comorbidities such as diabetes, obesity, congestive heart failure, fatty liver disease, depression and/or anxiety. Due to differences in the clinical manifestations of PSA, some patients are not diagnosed through clinical examination. Delayed psoriatic arthritis diagnosis or consultation has been related to low quality of life and increased frequency of comorbidities and persistent inflammatory state. The aim of the present study was to explore multiple etiologies of PSA, screening tools, and pharmaceutical therapy. Articles were searched from international databases including Magiran, Scopus, Google Scholar, PubMed, and Springer. The keywords of Psoriatic Arthritis, Screening tools, pathogenesis, treatment, and Biomarkers were used to extract articles.&#x0D; Conclusion: Our study showed that heterogeneity in the etiology of PSA was a major reason for classification problems within this disease spectrum. The explanation for this disease heterogeneity may be focused on variations in genetic and environmental factors. Screening strategies (ex: CASPAR criteria and biomarkers) are a significant first step in early treatment. Moreover, many types of therapy are available to help decreased joint problems, muscle weakness, and disease severity. Detection of dependent factors related to PSA might help in the early intervention of these patients to address clinical and para-clinical issues.&#x0D; Here we have provided an updated review of the early diagnosis, clinical features, pathogenesis, screening tools, biomarkers, and treatment recommendations, such as new biologic medications, for Psoriatic Arthritis.

Defining biological remission in Crohn's disease: interest, challenges and future directions.

In Crohn's disease, the treat-to-target strategy has been highly encouraged and became a standard of care. In this context, defining the target (remission) constitutes a major stake which fuels the literature. Currently, clinical remission (symptoms control) is no longer the only objective of treatments since it does not allow to well control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target was clearly a progress but this examination remains invasive, costly, not well accepted by patients and does not allow a tight control of disease activity. More fundamentally, morphological techniques (eg, endoscopy, histology, ultrasonography) are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggest that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalisation of inflammatory markers (C-reactive protein and faecal calprotectin): absence of biological signs associated with the risk of short-term relapse and mid/long-term relapse. The risk of short-term relapse seems essentially characterised by a persistent inflammatory state while the risk of mid/long-term relapse implicates a more heterogeneous biology. We discuss the interest of our proposal (guiding treatment maintenance, escalation or de-escalation) but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission.

Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar-Kyoto rats.

Chronic pain is often associated with comorbid anxiety and cognitive dysfunction, negatively affecting therapeutic outcomes. The influence of genetic background on such interactions is poorly understood. The stress-hyperresponsive Wistar-Kyoto (WKY) rat strain, which models aspects of anxiety and depression, displays enhanced sensitivity to noxious stimuli and impaired cognitive function, compared with Sprague-Dawley (SD) counterparts. However, pain- and anxiety-related behaviors and cognitive impairment following induction of a persistent inflammatory state have not been investigated simultaneously in the WKY rats. Here we compared the effects of complete Freund's adjuvant (CFA)-induced persistent inflammation on pain-, negative affect- and cognition-related behaviors in WKY vs. SD rats. Male WKY and SD rats received intra-plantar injection of CFA or needle insertion (control) and, over the subsequent 4 weeks, underwent behavioral tests to assess mechanical and heat hypersensitivity, the aversive component of pain, and anxiety- and cognition-related behaviors. The CFA-injected WKY rats exhibited greater mechanical but similar heat hypersensitivity compared to SD counterparts. Neither strain displayed CFA-induced pain avoidance or anxiety-related behavior. No CFA-induced impairment was observed in social interaction or spatial memory in WKY or SD rats in the three-chamber sociability and T-maze tests, respectively, although strain differences were apparent. Reduced novel object exploration time was observed in CFA-injected SD, but not WKY, rats. However, CFA injection did not affect object recognition memory in either strain. These data indicate exacerbated baseline and CFA-induced mechanical hypersensitivity, and impairments in novel object exploration, and social and spatial memory in WKY vs. SD rats.