Non-infectious Diseases Research Articles

The Integrated Impact of Metabolic, Dietary, Environmental, and Psychological Factors on Psoriasis – An Interdisciplinary Perspective on an Inflammatory Skin Disease

Introduction, purpose: Psoriasis is a chronic, non-infectious skin disease. It is estimated that approximately 2–3% of the global population is affected by this condition. Its prevalence varies geographically — higher rates are observed in Europe and North America, while lower rates are noted in Asia and Africa. The development of psoriasis is influenced by genetic predisposition, immune system dysfunction, as well as environmental factors. Psoriasis is not only a dermatological issue characterized by excessive keratinocyte proliferation, but also a systemic inflammatory disease that impacts the patient’s psycho-emotional well-being and carries an increased risk of numerous complications. Materials and methods: A literature review was conducted using the PubMed database to analyze the impact of patients' lifestyle on the course of psoriasis and the development of complications associated with this condition. Basic results: A holistic approach to patient care, which takes into account the various factors influencing the course of the disease and identifies areas of life that can be modified to enhance the overall health of the patient, is of significant importance in the pathogenesis of psoriasis. Conclusions: Although topical and systemic medications remain the cornerstone of psoriasis treatment, lifestyle modifications and health-promoting behaviors can contribute to a milder disease course, reduce the frequency of relapses, and lower the risk of comorbidities.

Advantages of using complement components in preventive and therapeutic vaccine strategies for infectious and non-infectious diseases.

The complement system, a vital component of innate immunity, is indispensable to our immune defence mechanisms against microbial infections. Acting as a surveillance mechanism, it identifies and eliminates pathogens by activating several complement components and associated signalling pathways, which are also implicated in various diseases and disorders. Beyond its defensive role, the complement system has emerged as a promising target for vaccine development in therapeutic and preventive regimens, offering new vaccine strategies to combat non-infectious and infectious diseases. Activation of the complement pathways by various natural and synthetic adjuvants enhances protective immune responses, highlighting its utility in vaccine design. This approach could be useful for targeting autoimmune diseases, infectious diseases, cancer and neurological disorders.

CD8+ T cell-based immunotherapy: Promising frontier in human diseases.

CD8+ T cell-based immunotherapy: Promising frontier in human diseases.

Case Report on Clinical Presentation of Foodborne Botulism

Botulism is an extremely dangerous infection caused by consuming food containing the botulinum toxin. It is classified as a foodborne toxic infection. Although botulism is relatively rare, it remains a significant health concern because it is difficult to diagnose, often resulting in late diagnoses and frequent fatal outcomes. Paresis and paralysis of smooth and skeletal muscles during botulinum toxin exposure often confuse healthcare professionals, leading to misdiagnosis and incorrect treatment. The article presents a case report of botulism in a female patient who was admitted to the intensive care unit (ICU) at the Botkin Clinical Infectious Diseases Hospital in 2024. The report clearly illustrates the clinical and laboratory challenges of diagnosing and treating this disease. The clinical presentation of botulism is similar to that of various infectious and non-infectious diseases. This underscores the importance of raising awareness and organizing health education initiatives, especially in primary outpatient settings, to encourage medical specialists to remain vigilant about botulism. It is crucial to educate the population systematically about the dangers of consuming improperly produced or stored canned foods in order to significantly reduce rates of botulism.

Prevalence and Correlates of Behavioural Risk Factors for Non‐Communicable Diseases Among Allied Health Undergraduate Students in Ghana: A Cross‐Sectional Study

ABSTRACTBackground and AimNon‐communicable diseases (NCDs) are noninfectious diseases mostly marked by complex aetiology with different risk factors. They develop from an interplay between modifiable and non‐modifiable risk factors, which are of great concern to the public as they mostly lead to varied metabolic changes. This study assessed the prevalence and correlates of behavioural risk factors of non‐communicable diseases among undergraduate allied health students in Ghana.MethodsThis was a cross‐sectional study that used a pretested and structured questionnaire to collect data from 228 participants. The data was analysed using SPSS. Logistic regressions and Chi‐squared tests were employed to assess the associations between sociodemographic factors and each NCD risk factor. Statistical significance was set at p ≤ 0.05.ResultsAbout 87.3% of undergraduate allied health students practised unhealthy dietary patterns. Only 45.2% were physically active. Being a Nonresident student was associated with drinking alcohol (OR = 2.5; 95%CI = 1.1–5.9). Male undergraduate students were less likely to be physically inactive (OR = 0.4; 95%CI = 0–0.9) while community nutrition students were less likely to engage in unhealthy diet practices (OR = 0.7; 95%CI = 0.2–1.3). Female proportions among those with one (60.7%, p = 0.02) and two (61.9%, p = 0.01) risk factors were high. A greater portion of the students with unhealthy dietary (81.4%, p = 0.032) and physical inactivity (69.5%, p = 0.010) patterns were 18‐24 years old. Most participants with one (61.8%, p = 0.04) and two (69.5%, p < 0.001) behavioural risk factors were all 18–24 years old.ConclusionThe findings of this study highlight a concerning trend of poor dietary habits and physical activity patterns among undergraduate allied health students. Despite being future healthcare professionals, these students exhibited suboptimal behaviours that can negatively impact their own health and well‐being, as well as their ability to provide effective health promotion and education to their future patients. Healthcare educators and administrators should recognize the importance of promoting a healthy campus environment that supports students' physical and mental well‐being.

Fever of unknown origin: Clinical significance of the etiology and common inflammatory parameters.

Fever of unknown origin: Clinical significance of the etiology and common inflammatory parameters.

Determining the influence of vegetable powders on the formation of ginger cookie quality

The object of this study is the technology of ginger cookies. A serious issue is the spread of non-infectious diseases: obesity, diabetes, cancer, intestinal diseases, etc. This is caused by the consumption of "refined" foods, lack of dietary fiber and other nutrients in diets. Therefore, it is important to fortify flour confectionery products with sources of useful nutrients. This paper has proven the effectiveness of using carrot powder to replace 10% of the total amount of flour and 4% of sugar and pumpkin powder to replace 15% and 6%, respectively, in the production of ginger cookies. Such solutions make it possible to fortify products with dietary fiber by 27.1% when adding carrot powder, and by 39.6% when using pumpkin powder. When using the latter, additional fortification with proteins occurs, by 23.1%. The addition of carrot powder helps reduce the glycemic index of ginger cookies by 5.1%, while the addition of pumpkin powder reduces this indicator within the margin of error. It was found that the addition of carrot and pumpkin powders in the specified quantities increases the stretchability of gluten by 11.8% and 38.0%, respectively. At the same time, the elasticity decreases by 6.5% and 30.4%, respectively. Therefore, the fortified products are more fragile and have more developed porosity. Also, the devised ginger cookies have a darker color. This is explained by the significant content of β-carotene in vegetable powders: 10.2 mg/100 g and 18.5 mg/100 g, respectively. In addition, the powders contain a significant amount of simple sugars, which enhances the melanoidin formation reaction and positively affects the color of the products. The results have practical significance for confectionery and craft manufacturers. The proposed technological solutions could make it possible to expand the range of ginger cookies with increased nutritional value and high quality indicators

Combination of chronic kidney disease with chronic non-infectious diseases

The scientific review examines chronic kidney disease (CKD) in combination with chronic non-communicable diseases. Chronic kidney disease is a serious and growing public health problem worldwide, characterized by a gradual and irreversible decline in kidney function and is one of the leading causes of death worldwide. The priority task of healthcare is the prevention of chronic non-communicable diseases, among which the most significant include cardiovascular diseases, bronchopulmonary diseases, diabetes mellitus, and oncological diseases. The association of CKD with chronic non-communicable diseases, in particular with cardiovascular diseases, makes this pathology especially dangerous, which leads to a deterioration in the quality of life of patients and an increase in mortality. The treatment of patients with comorbid pathology requires a comprehensive and interdisciplinary approach.

The Global Impact of International Public Health: Addressing Challenges of Globalization, Health Disparities, and the Importance of International Cooperation in Health Initiatives

Introduction: International public health is a vital discipline that aims to enhance the health of global populations. It addresses critical issues such as the prevention of infectious and non-infectious diseases, health policy formulation, and the examination of social and economic determinants of health.  Objective: This article aims to explore the impact of globalization on public health, highlighting the need for international cooperation to address health challenges that transcend national borders. It emphasizes the importance of collaborative efforts in managing pandemics and promoting health equity.  Literature Review: The review analyzes how globalization shapes health policies and impacts health disparities. It discusses mechanisms that enable effective international collaboration, such as the World Health Organization's frameworks during health emergencies. The review also considers lessons from recent crises, notably the COVID-19 pandemic, with a focus on vaccine equity and the necessity for robust health infrastructure.  Discussion: Globalization presents both opportunities and challenges for public health. While it facilitates access to healthcare resources and technology, it also exacerbates health inequalities, particularly in low-income countries. The interconnectedness brought about by globalization has implications for social determinants of health, migration patterns, and the rapid spread of infectious diseases. Cultural beliefs and practices further complicate public health responses, necessitating culturally sensitive strategies.  Conclusion: International public health is essential for preventing and responding to health crises. It highlights the importance of coordinated global efforts to address health disparities and improve health outcomes. By prioritizing evidence-based policies and fostering international partnerships, we can build resilient health systems that cater to diverse populations.

Clinical evaluation of two pathogen enrichment approaches for next-generation sequencing in the diagnosis of lower respiratory tract infections.

The underdevelopment of microbiological tests has contributed to diagnostic delay and inappropriate use of antibiotics in patients with lower respiratory tract infections, which is ranked as the seventh leading cause of death globally. Next-generation sequencing (NGS) has emerged as a promising platform for the diagnosis of infectious diseases, albeit with high costs and challenges in result interpretation. Here we evaluated two NGS-based pathogen detection assays for the etiological diagnosis of pneumonia in a prospective cohort of 257 patients. Both assays utilized multiplex polymerase chain reaction (PCR) for pathogen enrichment. One assay was designed to promiscuously amplify and identify more than 1,000 pathogens (broad-spectrum targeted next-generation sequencing [bs-tNGS]), while the other specifically targeted 194 pathogens (pathogen-specific targeted next-generation sequencing [ps-tNGS]). The analytical and diagnostic performances of both assays were compared using a composite clinical reference standard. The specificity of ps-tNGS was higher than that of bs-tNGS (84.85% vs. 75.00%), while the sensitivities of both assays were similar (>89%). In addition, a significant overlap in the frequently detected pathogens by the two methods was observed. Moreover, the enrichment of pathogens via multiplex PCR for ps-tNGS has alleviated the requirement for deep sequencing in the shotgun metagenomic workflows and thus dramatically lowered the assay cost. This study demonstrated that ps-tNGS achieved a better overall diagnostic performance and may potentially replace bs-tNGS in the clinical application.IMPORTANCEMicrobial enrichment in metagenomic next-generation sequencing has been achieved through differential cell lysis, but the results varied, depending on experimental procedures and sample types. Therefore, direct enrichment of pathogen DNA/RNA was attempted via multiplex PCR or hybrid probe capture (targeted next-generation sequencing [tNGS]). We evaluated two enrichment methods based on multiplex PCR. One method utilized a primer design strategy to amplify over 1,000 respiratory pathogens (bs-tNGS), while the other specifically targeted 194 pathogens (ps-tNGS). Our findings disavowed the notion that "the more, the better" in tNGS workflows, since ps-tNGS exhibited equivalent sensitivity and, notably, higher specificity than bs-tNGS in a prospective cohort of 257 patients who were suspected of having pneumonia. In future evaluations of tNGS assays, researchers should pay more attention to diagnostic specificity, rather than focusing solely on sensitivity, since a low specificity may potentially lead to misdiagnosis and overuse of antibiotics in cases of non-infectious diseases.

Management of Vipadika through Panchakarma w.s.r. to Palmoplantar Psoriasis: A Case Report

Introduction: Palmo-plantar Psoriasis is a non-infectious chronic inflammatory disease of the skin bound to the palm and soles in extent. In Ayurveda, all skin diseases are recounted under a single heading i.e., Kushtha (skin diseases). Palmo-plantar Psoriasis can be co-related with Vipadika (one of the Kshudra Kushtha described in Ayurveda), based on its clinical signs &amp; symptoms. Aim and Objective: To evaluate the effect of Virechana, Raktamokshan, and Snehapana in a Vipadika w.s.r. to palmoplantar psoriasis. Materials and Methods: In the present case, a 50-year-old female patient was diagnosed as a patient of Vipadika (palmoplantar psoriasis) having pruritic rashes on both palm and sole along with bloody and watery discharge from the same. The patient was treated with Shodhana therapy, which included Shodhnartha Snehapana, Virechana, Raktamokshana, and Shamana Aushadhi. Observation and Results: Significant results were observed in the SPI - Simplified Psoriasis Index (SPI score), as well as in itching and associated complaints. Discussion and Conclusion: Panchakarma therapies like Virechana, Raktamokshana, and Snehapana provide effective relief in the case of Vipadika in symptoms like itching, discharge and SPI score.

Causes of death in Magellanic penguins Spheniscus magellanicus in southern Brazil.

Magellanic penguins Spheniscus magellanicus are seasonal migratory seabirds. During the migratory period, these penguins are observed mainly in the seas of Argentina, Uruguay, and Brazil. Studies on mortality events in the species are limited, particularly those comparing free-ranging and captive penguins. This study describes the causes of death and pathological findings in Magellanic penguins using necropsy records from a retrospective study (2011-2021). Records from 164 penguins were analyzed, comprising 95 in captivity, 68 free-ranging, and 1 of undetermined origin. Non-infectious diseases (n = 104) were predominant in free-ranging penguins and included starvation (n = 49), suspected drowning (n = 27), hypothermia secondary to oil pollution (n = 25), trauma (n = 2), and intestinal obstruction (n = 1). Infectious/inflammatory diseases (n = 23) were most frequent among captive populations, including cases of malaria (n = 9), aspergillosis (n = 7), other mycotic infections (n = 3), bacterial infection (n = 2), protozoal meningoencephalitis (n = 1), and granulomatous air sacculitis of unknown origin (n = 1). Juvenile penguins constituted most cases in both non-infectious and infectious categories. There were 37 cases of undetermined diagnoses. Gastrointestinal parasitosis, cutaneous lesions, and pulmonary edema were the main secondary pathologic findings. These results enhance our understanding of the diseases affecting the Magellanic penguins and provide valuable insights for the conservation and maintenance of free-ranging and captive penguins.

RETROSPECTIVE ANALYSIS OF MORBIDITY AND MORTALITY IN NORTHERN SULAWESI BABIRUSA (BABYROUSA CELEBENSIS) IN NORTH AMERICAN ZOOLOGIC INSTITUTIONS FROM 1995 TO 2021.

Northern Sulawesi babirusa (Babyrousa celebensis) are endangered wild pigs native to the Indonesian island of Sulawesi. Since the 1970s, babirusa have been managed and bred in zoological institutions. To date, an analysis of the medical conditions affecting this species has not been reported. A retrospective study of the causes of morbidity and mortality in babirusa managed from 1995-2021 by Association of Zoos and Aquariums (AZA) accredited institutions in North America was performed. Medical (149) and associated pathology records (41) from babirusa at nine institutions were reviewed. Trends associated with age, sex, cause of death, disease process, and organ system were examined. Of the 503 morbidity events, the most common systems affected were musculoskeletal (n = 184), digestive (n = 119), and integumentary (n = 106). Adult males were more likely than adult females to experience dental trauma due to the presence of large maxillary canine tusks. The study population's average lifespan was 12.1 years for animals surviving at least one year, and females lived longer than males. Inflammatory processes were the cause of death in eight individuals. Non-infectious disease processes, particularly degenerative joint disease (n = 6), neoplasia (n = 5), and anesthesia-related (n = 5) were the other common causes of death/euthanasia. Organ systems most commonly affected by disease process causing mortality were the digestive (n = 11), musculoskeletal (n = 10), cardiovascular (n = 5), and respiratory (n = 5). Given the high prevalence of degenerative joint disease, captive management of babirusa should focus on developing strategies for early diagnosis, management, and prevention of joint disease. Consideration should also be given to the high incidence of tusk trauma, which may be decreased by modifications in exhibit design.

Impact of maternal health on neonatal and long-term kidney outcomes.

The increasing prevalence of non-communicable diseases like chronic kidney disease signals the need for a deeper understanding of the impact of the intra-uterine milieu on developmental programming and its impact on health outcomes through the lifespan of an individual. Maternal health in the pre-gestational and gestational phases, including nutrition, exposure to drugs, environmental toxins, infectious and non-infectious diseases, and socio-economic conditions influence the overall development of the fetus as well as the fetal kidney. The small, vulnerable newborn, born from an adverse developmental environment, is predisposed to low nephron number and is at risk for acute kidney injury in the neonatal period. Developmental programming has far-reaching consequences, including a higher risk for cardio-kidney-metabolic diseases, including hypertension and chronic kidney disease, and pregnancy complications, which perpetuates an intergenerational cycle of non-communicable disease risk. This risk can be mitigated by optimizing the care of individuals in the reproductive age group, identifying high-risk pregnancies early, and providing optimal treatment and monitoring. Care of the small vulnerable neonate includes prevention of acute kidney injury and life-long surveillance and modulation of cardio-kidney-metabolic risk. The review focuses on highlighting the influence of maternal health in the pre-gestational and gestational phases on kidney health from the neonatal period to adulthood.

Selected issues in the anatomy and physiology of the avian organ of vision and eye disorders in farmed poultry

The aim of this article was to review current knowledge of the anatomy and physiology of the avian eye and ocular diseases in poultry. The avian visual organ consists of the eye and extraocular organs and, unlike the mammalian eye, is characterised by many structural and functional adaptations that enhance vision. Avian eyes do not have the same functions as mammalian eyes. Bird eyes have high sensory sensitivity and are capable of constellation recognition for star orientation and navigation; they may be regarded as the finest ocular organs in the animal kingdom. It is generally accepted that the considerable differences in the morphology and function of avian eyes are largely due to adaptations to specific activities and environmental conditions. Eye diseases are rarely diagnosed in poultry because, unlike livestock and pets, detailed ophthalmological examinations are not carried out on farmed birds. Nevertheless, poultry are frequently affected by ocular pathologies, including developmental abnormalities, infectious and non-infectious diseases, degenerative processes, tumours, injuries and pathological conditions of unknown aetiology. In poultry, ocular disease is often associated with respiratory and systemic disease. Ocular pathology in farmed birds has a complex aetiology and its incidence can be reduced by controlling the incubation parameters of hatching eggs, avoiding feeding errors in breeder flocks and rearing poultry under conditions that optimise welfare and comply with biosecurity standards.

Fluorescent bead-based multiplex assays improve serological disease diagnostics and have potential of identifying sensitive immune biomarkers for maintaining health and performance.

Fluorescent bead-based multiplex assays (multiplex assays) for serological detection of antibodies in patient samples have been used in veterinary diagnostics for a little over a decade. These quantitative assays offer several advantages compared to classical serological assays, like a lower limit of detection, less background, and a broader linear quantification range, all of which improve test accuracy. The simultaneous multiplex analysis of a patient's serological response to several specific antigens also improves the diagnostic result interpretation. This influences treatment and management decisions and often allows for a quantitative follow-up as treatment response evaluation. In this review article, we discuss examples of 3 diagnostic multiplex assays for antibody detection in veterinary patients: the Lyme Multiplex assay, the Canine Brucella Multiplex assay, and the Equine Herpesvirus Type-1 Risk Evaluation assay. In addition, multiplex assays for immune response markers, like soluble cytokines, chemokines, or other inflammatory proteins, have recently become available. Currently, these assays are mainly used as clinical research tools to broadly evaluate immune activation and/or inflammation during a variety of infectious and noninfectious diseases. Quantitative cytokine and inflammatory marker multiplex assays have the potential to identify sensitive immune biomarkers for maintaining health and performance in veterinary animals.

Application value of metagenomic next-generation sequencing based on protective bronchoalveolar lavage in nonresponding pneumonia.

This study aims to explore the application value of metagenomic next-generation sequencing (mNGS) of protective bronchoalveolar lavage fluid in the differential diagnosis and pathogenetic identification of nonresponding pneumonia. This study analyzed patient symptoms, auxiliary examinations including pathogen detection, and treatment response to identify the reasons for the lack of response to initial treatment and the pathogenetic diagnosis of pulmonary infections. The diagnostic efficacy of pathogen culture and mNGS was statistically analyzed and compared based on the clinical diagnosis criteria. (1) The two most common reasons for the ineffectiveness of initial treatment in nonresponding pneumonia cases are that (i) the initial treatment did not cover the pathogenic bacteria in pulmonary infection cases and that (ii) non-infectious pulmonary diseases were responsible. The most common pathogens in pulmonary infection cases of nonresponding pneumonia are Mycobacterium tuberculosis (MTB), Pneumocystis jirovecii, Aspergillus, and Pseudomonas aeruginosa. (2) In pulmonary infectious cases, mNGS demonstrated a higher detection sensitivity for pathogenic bacteria than pathogen cultures. mNGS combined with protective bronchoalveolar lavage has good clinical application value in the accurate diagnosis of pathogens and identification of non-infectious diseases.IMPORTANCEThe combination of mNGS and the protective BAL technique demonstrates significant utility in accurately diagnosing pathogens and identifying non-infectious diseases. Misdiagnosis of non-infectious lung diseases as infectious lung diseases is a common factor contributing to the lack of response to initial treatment in nonresponding pneumonia patients. The most common pathogens in pulmonary infection cases of nonresponding pneumonia are MTB, Pneumocystis jirovecii, Aspergillus, and Pseudomonas aeruginosa.

Exploring the Interaction Mechanisms of Antibody-Mediated Immune Responses with Gout and Rheumatoid Arthritis Through a Bidirectional Two-Sample Mendelian Randomization Study

PurposeGout and Rheumatoid arthritis (RA) are two prevalent non-infectious inflammatory joint diseases that can occur independently or concurrently. The effects and mechanisms related to antibody-mediated immune responses and both Gout and RA remain unclear. The research seeks to investigate the potential causal association and offer a novel perspective for their prevention and treatment strategies.MethodsThe study employed the bidirectional two-sample Mendelian randomization (MR) analysis for investigation. Datasets comprising 46 antibody-mediated immune responses, as well as those for Gout and RA, were curated from published genome-wide association studies (GWAS). For the causality analysis, methods such as Inverse Variance Weighted (IVW), Weighted Median, Simple Mode, MR-Egger, and Weighted Mode were utilized. We chose MR pleiotropy residual sum and outlier (MR-PRESSO), IVW, MR-Egger, and Leave-one-out for sensitivity analysis to enhance the reliability of the results.ResultsWe meticulously excluded the results that exhibited pleiotropy and instability. Finally, four antibody-mediated immune responses have been found as causal factors in the development of Gout: Anti-chlamydia trachomatis IgG seropositivity, Anti-human herpes virus 6 IE1B IgG seropositivity, Helicobacter pylori GroEL antibody levels, and Polyomavirus 2 JC VP1 antibody levels; Two antibody-mediated immune responses influence RA causally: BK polyomavirus VP1 antibody levels, and Helicobacter pylori Catalase antibody levels. In the reverse analysis, three antibody-mediated immune responses could be influenced by Gout: BK polyomavirus VP1 antibody levels, Chlamydia trachomatis tarp-D F2 antibody levels, and Varicella zoster virus glycoproteins E and I antibody levels; Two antibody-mediated immune responses could be causally affected by RA: Anti-human herpes virus 7 IgG seropositivity, and Merkel cell polyomavirus VP1 antibody levels.ConclusionThe research indicated that antibody-mediated immune responses establish a causal link with this two non-infectious inflammatory joint diseases: Gout and RA, offering new avenues and perspectives for the future prophylaxis and treatment of diseases from an immunological standpoint.

Astrocyte-derived CCL5-mediated CCR5+ neutrophil infiltration drives depression pathogenesis.

Cross-talk between the nervous and immune systems is involved in neurological diseases. However, their potential interplay in depression has yet to be elucidated. Here, using single-cell RNA and neutrophil SMART RNA sequencing, we showed that CCR5+ neutrophils were significantly increased in patients with depression and preferentially migrated to the hippocampus in a mouse model of depression. Infiltrated neutrophils engulf neuronal spines and subsequently promote depressive symptoms in male mice. Furthermore, by genetic or pharmacologic disruption, we identified a chemotactic effect of the astrocyte-derived chemokine CCL5 on mediating the infiltration of CCR5+ neutrophils and behavioral disorders in male depressed mice. Our findings therefore highlight the critical role of neutrophils in depression pathogenesis and astrocytes in mediating the dysregulation of innate immune responses and suggest that inhibition of CCL5/CCR5-mediated neutrophil infiltration represents a potential therapeutic strategy for noninfectious brain diseases such as depression.

Pathways to Progressive Disability in Multiple Sclerosis: The Role of Glial Cells in Chronic CNS Inflammation.

Multiple sclerosis (MS) is the most common non-infectious inflammatory CNS disease, characterized by progressive neurodegeneration and focal demyelinated lesions. Traditionally considered an autoimmune disease, MS is driven by the immune system's attack on CNS myelin, resulting in cumulative disability. However, conventional anti-inflammatory treatments often fail to prevent progressive deterioration, particularly in the absence of overt inflammation, highlighting the need for a deeper understanding of its pathogenesis. Recent research has revealed a more complex disease mechanism involving both peripheral immune responses and intrinsic CNS factors, with glial cells playing a central role. Persistent inflammation in MS is associated with mixed active/inactive lesions dominated by microglia and astrocyte dysregulation. These glial populations exhibit maladaptive activation, contributing to failed remyelination and ongoing neurodegeneration. Transcriptomic and epigenomic alterations as well as aging further exacerbate glial dysfunction, creating a self-perpetuating cycle of inflammation and damage. Emerging evidence suggests that the interplay between peripheral immune cells and glial populations and the potential dual-use nature of molecular tools shared by the immune system and CNS disrupts homeostatic signaling, leading to a loss of tissue integrity. This review synthesizes findings on glial cell biology in MS, with a focus on microglia and astrocytes, while addressing their roles in demyelination, synapse loss, and neurodegeneration. The limitations of animal models, particularly EAE, in replicating the complexity of MS are also addressed. Finally, critical questions are outlined to guide future research into glial pathology and to identify novel therapeutic approaches targeting progressive MS.