Autoimmune Conditions Research Articles

Carvone-loaded chitosan nanoparticles alleviate joint destruction by downregulating the expression of pro, inflammatory cytokines and MMP-13 in adjuvant-induced rat model.

Rheumatoid arthritis is an autoimmune illness causing deformity, edema, and joint tenderness. Its long-term treatment burdens the healthcare system and leads to toxicity, and thus, finding safe, effective, and affordable therapies is essential. The current study aimed to exhibit the anti-arthritic activity of Carvone-loaded chitosan nanoparticles to treat Freund's complete adjuvant (FCA) arthritis in rats. Healthy albino rats (n = 35) were distributed into seven groups. The 1st group worked as normal control, while the 2nd was arthritic control. The 3rd group received methotrexate (10mg/kg/week). The 4th group received Carvone (60mg/kg/day), while the 5th (30mg/kg/day), 6th (45mg/kg/day), and 7th (60mg/kg/day) groups received Carvone-C-NPs, respectively. Nanoparticles, prepared by the ion gelation method, were characterized by zeta size, potential, scanning electron microscopy, and Fourier transform infrared microscopy. NPs have zeta size (78.82 ± 0.02nm) and potential (19.96 ± 0.02mV). A significant reduction was shown in paw swelling (5.52 ± 0.05mm), arthritic score (2.81 ± 0.23), and rheumatoid factor (14.56 ± 0.68IU/L) by Carvone-C-NPs. qRT-PCR results showed significant down-regulation of pro-inflammatory cytokines [TNF-α (0.25 ± 0.03), IL-1β (0.21 ± 0.06), IL-17a (0.16 ± 0.12), and IL-33 (0.15 ± 0.01)] and up-regulation of anti-inflammatory cytokines [IL-4 (0.85 ± 0.06) and IL-10 (0.66 ± 0.04)] in ankle joint of Carvone-C-NPs treated group. The radiographical and histopathological findings showed reduced pannus formation, joint swelling, and synovial hyperplasia in the Carvone-C-NPs treated group. Overall, it is concluded that Carvone-C-NPs have remarkable anti-arthritic activity and promising anti-inflammatory properties.

Age-Dependent Bi-Phasic Dynamics of Ly49+CD8+ Regulatory T Cell Population.

Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4+Foxp3+ regulatory T cells (Tregs) have been well documented. However, the nonredundant Foxp3-CD8+ Tregs were never examined in the context of aging. This study first established clear distinctions between phenotypically overlapping CD8+ Tregs and virtual memory T cells. Then, we elucidated the dynamics of CD8+ Tregs across the lifespan in mice and further extended our investigation to human peripheral blood mononuclear cells (PBMCs). In mice, we discovered a bi-phasic dynamic shift in the frequency of CD8+CD44hiCD122hiLy49+ Tregs, with a steady increase in young adults and a notable peak in middle age followed by a decline in older mice. Transcriptomic analysis revealed that mouse CD8+ Tregs upregulated a selected set of natural killer (NK) cell-associated genes, including NKG2D, with age. Importantly, NKG2D might negatively regulate CD8+ Tregs. Additionally, by analyzing a scRNA-seq dataset of human PBMC, we found a distinct CD8+ Treg-like subset (Cluster 10) with comparable age-dependent frequency changes and gene expression, suggesting a conserved aging pattern in CD8+ Treg across mice and humans. In summary, our findings highlight the importance of CD8+ Tregs in immune regulation and aging.

Lupus and SARS-CoV-2: What have we learned after the pandemic?

After the end of the COVID-19 public health emergency, we analysed the relationship between Systemic Lupus Erythematosous (SLE) and COVID-19 from the virologist's perspective based on recent findings. SLE and COVID-19 co-morbidity present unique challenges, as individuals with SLE may be at increased risk for severe COVID-19 illness due to immune system abnormalities and ongoing therapies. Effective management of both diseases requires careful monitoring, adherence to vaccination programs, preventive measures and approved and patient-tailored therapies. This review covers various aspects, including the clinical outcome of SLE patients infected by SARS-CoV-2, the impact of this infection on SLE onset or flare-ups and the benefits of vaccination for this population. Furthermore, this review presents the most recent recommendations on clinical management of COVID-19 in rheumatic patients, including those with SLE, discussing the currently available therapeutic options. Finally, we explore the most effective tools for SARS-CoV-2 diagnosis in autoimmune conditions and examine prognostic biomarkers in COVID-19 rheumatic patients with potential implications on their clinical oversight. By adopting a comprehensive approach, we address these complexities from the virologist's perspective, aiming to improve health care for this vulnerable population.

Higher risk profile among patients with TET2-mutated giant cell arteritis: a cluster analysis

ObjectiveWe aimed to assess the prevalence of clonal haematopoiesis (CH) in patients with giant cell arteritis (GCA) compared with controls and individuals with other autoimmune diseases (AIDs) and to identify...

Effectiveness of Bacterial Lysates as Immune-Boosting Supplements: Evaluating a Novel Approach to Immune Health

The increasing prevalence of recurrent infections and immune-related disorders has intensified the search for effective immune-modulating interventions. Bacterial lysates, derived from inactivated bacterial components, have emerged as promising immune-boosting supplements. These lysates activate both innate and adaptive immune responses by interacting with pattern recognition receptors such as Toll-like receptors (TLRs), triggering signaling pathways that enhance immune surveillance and pathogen recognition. Among the most extensively studied is OM-85, which has demonstrated efficacy in reducing the frequency and severity of respiratory tract infections (RTIs) and modulating immune pathways involved in asthma and allergic rhinitis. This review evaluates the mechanisms of action, clinical efficacy, and safety profiles of bacterial lysates, particularly focusing on their role in preventing RTIs and managing chronic inflammatory diseases. Evidence supports their potential to reduce antibiotic use and improve overall clinical outcomes in both pediatric and adult populations. Despite their general safety, certain contraindications exist, especially in patients with hypersensitivity or autoimmune conditions. Further research is required to optimize their use, particularly in immunocompromised populations and for broader applications, such as viral infections. Bacterial lysates represent a novel, cost-effective approach to enhancing immune health and reducing the global reliance on antibiotics.

Effective management of Kitibha Kushta (Scalp Psoriasis) through Ayurveda: A Case Report

Introduction:- In today’s era where the lifestyle scenario became more sedentary, including improper habit of eating food, lack of physical exercise, unhygienic conditions which leads to risk of many skin diseases like psoriasis. Psoriasis is a long term auto-immune dermatological condition in which there is itching all over the body, dryness & redness of skin and scaling appears on the affected site. In Ayurveda psoriasis can be correlated with Kitibha Kushta is a type of Kshudra Kushta exhibiting in the form of lesions with Shyava Varnata, Kina-Khara Sparsha, Parushata etc. Methodology: A 48 years old female patient came with the chief complaints of flaky skin lesions over the scalp, ears and eyebrows since 2-3 years, associated with severe itching on the lesions. The case was diagnosed as Kitibha Kushta and managed with Samshodhana and Samshamana Chiktsa successfully. Result: The patient reported a significant improvement in the complaints. Conclusion: Kitibha Kushta is a Vata- Kapha Pradhana Tridosaja Vyadhi Classical Vamana Karma was done with Madanaphala, Indrayava, Yastimadhu, Patola, Nimba. Classical Vamana karma is very effective in Kitibha Kushta due to its Sodhana property.

Decoding Dystonia in Autoimmune Disorders: A Scoping Review.

Dystonia is a common hyperkinetic movement disorder observed in various genetic, infective, drug-induced, and autoimmune disorders. Autoimmune disorders can present with isolated or combined acute or subacute dystonia. The pattern and approach to dystonia in autoimmune disorders are poorly described and have never been established in a structured manner. This scoping review aims to summarize all available clinical literature and formulate a pattern and approach to dystonia in different autoimmune disorders. We included one hundred and three articles in this scoping review. Most articles identified were case reports or case series. In this review, we analysed data from 103 articles and summarized the epidemiological, clinical, and diagnostic features of dystonia associated with different autoimmune diseases. We highlight that dystonia can be isolated or combined in various autoimmune conditions and is responsive to immunotherapy. We point out the patterns of dystonia and associated neurological features and investigations that can suggest the underlying autoimmune nature, which can guide the most appropriate treatment. The clinical pattern of dystonia can be a unique feature in many autoimmune disorders. In isolated subacute dystonia, the presence of autoantibodies could have a temporal association, or this is just an epiphenomenon to be evaluated in further research. Many autoimmune disorders can present with isolated or combined dystonia.Subacute onset focal or segmental dystonia (craniocervical dystonia or limb dystonia) or hemidystonia could be secondary to an autoimmune condition and warrants investigations.They have a relapsing or progressive course.They usually have a good response to early immunotherapy.Symptomatic treatment, including botulinum toxin, can be useful in focal dystonia.

Resolution of acute motor axonal neuropathy in a patient after treatment with efgartigimod: A case report.

Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy characterized by progressive muscle weakness, often caused by immunoglobulin G (IgG) autoantibodies. There are several subtypes of GBS, of which acute motor axonal neuropathy (AMAN) is one of the most severe subtypes associated with axonal damage. It is well known that the current clinical standard of treatment is intravenous immunoglobulin (IVIg) and plasma exchange (PLEX), but some patients often show limited response or experience persistent disability. Efgartigimod, an Fc fragment of human IgG antibody, provides a way to target and reduce pathogenic IgG antibodies as a natural ligand Fc receptor (FcRn). The purpose of this study was to observe the therapeutic effect of efgartigimod on axonal GBS, which is expected to be a potential therapeutic method for GBS and AMAN. We present a case of a 58-year-old man diagnosed with AMAN, presenting with ascending symmetrical limb weakness, flaccid paralysis, and multiple cranial nerve palsies. Electromyography confirmed the axonal subtype of GBS. Despite receiving IVIg and PLEX, the patient showed suboptimal recovery. Subsequently, he was treated with efgartigimod at a dose of 10 mg/kg weekly for 4 weeks, demonstrating significant improvement in both clinical symptoms and electromyographic findings, with good tolerability. This case highlights the potential efficacy and safety of a 4-dose efgart-igimod regimen in AMAN, particularly for patients with inadequate response to conventional therapies. By targeting FcRn and promoting IgG degradation, efgartigimod offers a novel mechanism to modulate the aberrant immune response underlying AMAN. Efgartigimod at a dose of 10 mg/kg weekly for 4 weeks demonstrated promising results in this case of AMAN. While further research is warranted, our findings suggest that efgartigimod may represent a valuable addition to the therapeutic armamentarium for AMAN and potentially other autoimmune neurological conditions. Well-designed clinical trials are crucial to confirm these findings and establish optimal treatment protocols for efgartigimod in AMAN.

Herpes simplex virus type 2 in sub-Saharan Africa and the potential impact of helminth immune modulation.

Herpes simplex virus type 2 (HSV-2) and helminth infections are among the most widespread infectious diseases in sub-Saharan Africa (SSA). Helminths are known to modulate host immune responses and consequently impact the severity and outcomes of unrelated diseases, including allergies, autoimmune conditions, and infectious diseases. In this way, helminths may modulate essential immune responses against HSV-2 during co-infection and may alter susceptibility to and pathology of HSV-2. However, the epidemiology of STH/HSV-2 co-infections is understudied, and whether helminths influence the host immune response to HSV-2 is not well understood. In this perspective piece, we briefly examine the current knowledge on helminth immune modulation of important pathogens that are endemic to SSA, arguing that it is important to explore HSV-2 and helminth co-infections to elucidate potential interactions between HSV-2 and helminths. This is particularly relevant in SSA, where both pathogens are highly prevalent.

Association between Rheumatoid Arthritis Disease Activity and Comorbidities

Background and objectives: Rheumatoid arthritis is an autoimmune condition marked by chronic joint inflammation, frequently resulting in substantial impairment and diminished quality of life. However, rheumatoid arthritis rarely occurs in isolation, as individuals with this condition frequently present with comorbidities, such as cardiovascular disease, diabetes, and osteoporosis. Understanding the role of comorbidities in Rheumatoid Arthritis is critical for comprehensive patient care. The aim of this study was to investigate the impact of various comorbidities on disease activity of rheumatoid arthritis. Methods: Patient data for this cross-sectional study was collected at rheumatology outpatient of Rizgary teaching hospital in Erbil city of Kurdistan-Iraq from August 2022 August 2023. Study participants included patients with rheumatoid arthritis with (n=60) and without (n=60) comorbidities and they were matched for age and sex. Results: Our findings revealed that among patients with rheumatoid arthritis, hypertension is the most frequent comorbidity, affecting 27 patients (45%) of them. This is followed by the coexistence of hypertension and diabetes mellitus in 9 (15%) of cases, and hypothyroidism in 8 (13.3%) of cases. Furthermore, the study establishes a strong and statistically significant link between patient age and the presence of comorbidities (p<0.001). Additionally, it demonstrates a significant correlation between the high activity of RA disease and comorbidities (p=0.03). Conclusions: This research is providing insights into the ways in which these accompanying medical conditions affect the activity of rheumatoid arthritis. The results of this current study have important implications for making treatment choices, assessing risks, and crafting customized approaches to managing this disease.

The Role of Chronic Infections in Immune System Dysregulation and Autoimmune Diseases

Chronic infections significantly impact the immune system, contributing to dysregulation and the development of autoimmune diseases. Persistent pathogens, such as viruses and bacteria, can evade immune clearance, leading to a sustained inflammatory response that disrupts the delicate balance of immune tolerance and activation. This review explores the mechanisms through which chronic infections influence immune system dynamics, focusing on the role of cytokines, immune cell modulation, and the alteration of immune signaling pathways. Infections like hepatitis C, Epstein-Barr virus, and others have been linked to autoimmune conditions such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The persistent presence of these pathogens may lead to molecular mimicry, epitope spreading, and the activation of autoreactive T and B cells, driving the pathogenesis of autoimmunity. Additionally, we discuss the implications of chronic infections on therapeutic strategies for autoimmune diseases, emphasizing the need for a comprehensive understanding of the interplay between infections and autoimmune dysregulation. By elucidating the complex relationships between chronic infections and the immune system, this review aims to highlight potential avenues for developing targeted interventions and improving patient outcomes in autoimmune disorders. Keywords: Chronic Infections, Immune Dysregulation, Autoimmune Diseases, Cytokines, Pathogenesis

Cystatin D serum level in rheumatoid arthritis and its relation to disease activity

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune condition that causes synovitis and functional impairment. Currently, the most often utilized biomarkers for monitoring disease activity and severity are acute phase proteins, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).However, discrepancies have been found between the clinical inflammation and their levels. Therefore, there is a strong need for a novel biomarker to forecast how RA will proceed clinically and monitor the response to therapy. This study assessed the diagnostic value of serum cystatin D in RA patients and its potential as a biomarker for disease activity monitoring.ResultsRA patients had considerably greater serum levels of cystatin D than the control group. These values showed a positive correlation with Disease Activity Score-28 (DAS28), ESR, CRP, grayscale synovitis, power Doppler synovitis, grayscale tenosynovitis (p < 0.001), and erosions, sum scores (p < 0.05). Nonetheless, no noteworthy association was observed between the serum cystatin D levels and sociodemographic data, rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP).ConclusionCystatin D serum levels are higher in RA patients compared to healthy subjects and are strongly correlated with the activity of RA. It can be a valuable biomarker for evaluating RA disease activity.

Immune Checkpoint Inhibitor-Associated Celiac Disease: A Retrospective Analysis and Literature Review

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade, which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. A comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-induced celiac disease. Regarding pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to a rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and the discontinuation of antineoplastic immunotherapy.

Microfluidic Nanobioplatform-Based Immunosensor for Monitoring of 25-Hydroxy Vitamin-D3

Abstract Measurement of 25-hydroxyvitamin-D3 (25-VitD3) is crucial because its deficiency is linked to a variety of disorders, including osteoporosis, diabetes, depression, some autoimmune conditions, and even Covid-19. Hence, it is important to find new methods for efficient rapid testing for clinical diagnosis and public health prevention. Here, a new nanomaterial-based microfluidic electrochemical immunosensor towards the determination of 25-VitD3 using microwave synthesized gadolinium oxide nanoparticles (GdNPs) is presented. Mask-less lithography was used to create a micro-fluidic nano-bioplatform (MNBP) and three-electrode immunosensor on a transparent indium tin oxide (ITO) coated glass substrate. To fabricate MNBP (BSA/AB-25VitD3/CS@GdNPs/ITO), the working electrodes were functionalized with GdNPs, AB-25VitD3, and BSA (bovine serum albumin) in that order. The electrochemical response induced by the immunocomplex was measured in individual 25-VitD3 concentrations (1-100 ng mL-1). This immunosensor exhibited a higher sensitivity of 5.99 ng mL-1, limits of detection of 4.5 ng mL-1, and an analysis time of 30 minutes. In addition, clinical serum samples from three healthy people were used to validate the MNBP-based immunosensor, which showed a strong correlation with traditional enzyme-linked immunosorbent assays. The use of proposed immunosensor to serum samples would allow early detection of 25-VitD3 deficiency, particularly in rural and resource-constrained settings.

Hematological ratios as an indicator of severity in alopecia areata: A retrospective nationwide study.

Alopecia Areata (AA) is an autoimmune condition where the activation of Th1, Th2, and Th17 responses is known to stimulate other white blood cells, potentially affecting hematopoietic lineages. However, previous studies on AA have found no utility in hematological ratios. Our goals were to compare neutrophils-to-lymphocytes ratio (NLR), platelets-to-lymphocytes ratio (PLR), eosinophils-to-lymphocytes ratio (ELR), eosinophils-to-neutrophils ratio (ENR), and eosinophils-to-monocytes ratio (EMR) between patients with AA and controls, as well as between mild and moderate-severe AA cases. We performed a retrospective, population-based cohort study involving adult patients enrolled in the largest national health maintenance organization in Israel. The study comprised 147,020 AA patients and 141,598 healthy controls. AA patients exhibited a higher likelihood of elevated NLR and ELR compared to controls. Upon further classification based on severity, moderate-severe AA patients displayed higher values of NLR, PLR, ELR, and EMR compared to mild AA individuals OR = 1.11 [1.09-1.1], P<0.001; OR = 1.09 [1.05-1.13], P<0.001; OR = 2.06 [1.67-2.53], P<0.001; OR = 1.07 [1.03-1.07)], P<0.001, respectively). Similar trends were observed 12 to 18 months before diagnosis. Our results not only deviate from the current literature but also offer a cost-effective, accessible, and efficient tool for enhanced disease prediction and management.

Regulatory Impact of Selected U.S. FDA Postmarketing Safety Registries Conducted for Drugs Used to Treat Inflammatory or Autoimmune Conditions.

Assess the regulatory impact of selected FDA postmarketing safety registries on drug product labeling updates. Postmarketing safety studies were identified in internal record repositories for the Center for Drug Evaluation and Research, U.S. FDA, in March and September 2021. Studies eligible for review included prospectively enrolling patient registry studies conducted to assess the safety of drug products used to treat inflammatory or autoimmune conditions. These studies were requested between 1999 and 2011. This paper analyzed 10 safety (non-pregnancy) registries and four pregnancy registries (n = 14). Only four safety registry studies were successful in reaching their targets for both patient enrollment and patient follow-up or drug exposure. These registries were either multi-center, multinational studies or studies using participants from a health insurance or health maintenance organization. None of the safety registries led to safety labeling updates, regardless of targets' achievement for study enrollment and follow-up: six did not detect a new safety signal and four provided inconclusive results. Two pregnancy registries reached their targets for patient enrollment, and all four resulted in safety labeling updates, as required by the Pregnancy and Lactation Labeling Rule guidance. While six non-pregnancy registries did not detect a new safety signal, four did not produce safety results considered sufficiently robust to warrant specific regulatory action including safety-related labeling updates. The lack of safety signal detection in these observational studies should not imply the absence of safety signals. Appropriately designed, prospective, randomized controlled safety studies are the most reliable way to obtain interpretable safety data.

The West: An autoimmune disease?

ContextThis work explores the paradoxical stress mechanisms in Western societies, marked by consumption and comfort. Despite the perceived well-being of modern capitalist societies, a profound psychosomatic discontent manifests, reflected in the rise of stress-induced illnesses, autoimmune diseases, and psychiatric disorders. The article uses the metaphor of autoimmunity to describe Western societal dysfunction, drawing parallels between biological self-destruction and societal self-harm driven by hyper-individualism, economic pressures, and digital dependencies. ObjectivesThis study aims to analyze the mechanisms through which Western societies contribute to self-destructive processes, paralleling the way autoimmune diseases function within the body. It seeks to demonstrate how excessive control, consumerism, and the digital environment exacerbate stress, which in turn contributes to both physical and psychological deterioration. The philosophical question underpinning this analysis is whether the societal and economic systems in the West are undermining the self-defense mechanisms of their members, akin to an autoimmune response. MethodThe article adopts a qualitative and theoretical approach, integrating concepts from psychology, psychoneuroimmunology, and epidemiology. The author incorporates clinical observations, epidemiological data, and philosophical reflections to explore the effects of chronic stress on mental and physical health. Drawing on psychoneuroimmunology, the research explores the bi-directional interaction between the mind, nervous system, and immune function, focusing on the relationship between stress, inflammation and autoimmune diseases. ResultsOur exploration reveals a significant correlation between the rise of autoimmune diseases and the psychosocial stresses of Western capitalist societies. Epidemiological data support the link between chronic stress, psychiatric disorders, and autoimmune conditions. The article also highlights how the digital economy's manipulation of stress and fear (such as through FOMO) contributes to widespread psychological distress. This stress, in turn, disrupts immune function, leading to a cycle of physical and psychological degeneration. InterpretationWestern societies, through their relentless pursuit of control, comfort, and consumption, create environments of heightened stress that mirror the dysfunctions of autoimmune diseases, where the body turns against itself. The research suggests that modern capitalist structures are pathogenic, exacerbating stress, weakening immune resilience, and fostering mental health crises. The article concludes that a holistic approach is necessary to address this systemic dysfunction, advocating for a reconceptualization of health that integrates mental, physical, and societal well-being.

Ferroptosis: mechanisms and therapeutic targets.

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis-targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6-methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis-targeted therapies in the context of human health and disease.

Association Between Interleukin 27 and Different Types of Autoimmune and Dermatological Conditions: A Systematic Review

Association Between Interleukin 27 and Different Types of Autoimmune and Dermatological Conditions: A Systematic Review

Rheumatoid arthritis: a review of the key clinical features and ongoing challenges of the disease.

Rheumatoid arthritis (RA) is an autoimmune inflammatory condition that primarily affects the joints and periarticular soft tissue. The development of joint swelling is traditionally regarded as the starting point of the disease. Emerging evidence indicates that RA patients often experience a preclinical stage characterized by immunological and inflammatory changes before developing the disease. The review discusses ongoing efforts to predict the transition from this preclinical phase to clinical RA and describes studies aimed at preventing the onset of RA in individuals at risk. Over the past two decades, there have been significant advancements in RA management and outcomes. An increasing number of patients can now achieve disease remission, and in some cases, this remission persists without ongoing treatment, which is effectively a cure. As new therapies and evolving scientific evidence emerge, recommendations for RA management are continuously evolving. Despite these improvements in the management of RA, many patients still do not respond to multiple conventional or more advanced therapies, including biologic and targeted synthetic disease modifying anti-rheumatic drugs, or experience disease flares when treatments are tapered or discontinued. This situation underscores the need for reliable biomarkers to guide therapy more effectively, improve personalized treatment approaches and monitoring strategies (i.e. precision medicine). In conclusion, this review provides a comprehensive overview of RA, covering new research on the 'pre-clinical' phase of the disease, as well as its epidemiology, pathogenesis, clinical manifestations, diagnosis, imaging, and management strategies. It highlights key clinical aspects of RA and addresses ongoing challenges in disease management, particularly in the areas of prevention and treatment.