Progressive Inflammatory Disease Research Articles

Advances in the Treatment of Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, liver failure, or even death. While most patients respond well to first-line treatments, a significant number experience poor responses or intolerance, requiring the use of second- or third-line therapies. Ongoing research into the pathogenesis of AIH is leading to the development of novel therapeutic approaches. This review summarized recent advancements in the treatment of AIH both domestically and internationally.

Health-related quality of life disparity in cardiac sarcoidosis versus other myocardial diseases

Abstract Background Sarcoidosis, a systemic inflammatory disorder, can manifest as progressive inflammatory heart disease, termed cardiac sarcoidosis (CS). Despite advances in treatment, the impact of CS on health-related quality of life (HRQoL) remains incompletely understood. This study aimed to compare HRQoL between patients with CS and those with non-inflammatory cardiomyopathies, namely dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Purpose To assess and compare HRQoL across patients with cardiac sarcoidosis and non-inflammatory cardiomyopathies. Methods A total of 240 CS patients (86% response rate), 96 DCM patients (55% response rate), and 81 HCM patients (65% response rate) completed the RAND-36 general health-related questionnaire, comprising eight dimensions. Patients listed for transplantation were excluded. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry for CS patients and from medical records in hospitals for HCM and DCM patients. Results Median age ranged from 56 to 59 years across the groups. Unlike DCM, which typically presents with heart failure symptoms, a substantial proportion (82%) of CS patients presented with advanced atrioventricular block or ventricular arrhythmias, while HCM cases were often incidentally detected or identified through family screening. Most CS patients (94%) had implanted pacemakers or ICDs, compared to a lower proportion in HCM (26%) and DCM (63%). DCM patients exhibited a higher prevalence of impaired LVEF (<50%) compared to CS and HCM patients. Functional impairment, as measured by NYHA class, was most pronounced in DCM patients. CS patients experienced more adverse events between diagnosis and the study entry, particularly sustained ventricular tachycardia/ventricular fibrillation. However, heart failure hospitalizations did not significantly differ between groups. Table 1 presents a comparative analysis of patient-reported outcomes across four functional and mental dimensions to assess the relative burden of disease among patients with CS, HCM, and DCM. While the functional dimensions in CS exhibited disparities from both HCM and DCM, no significant differences were observed in the mental dimensions between CS and HCM. CS patients reported lower scores in the domains of role physical, and general health compared to either HCM or DCM counterparts. Conclusion Patients with CS demonstrated significantly poorer HRQoL compared to those with non-inflammatory cardiomyopathies. This underscores the substantial burden of disease associated with CS and highlights the importance of comprehensive management strategies to address both clinical and quality of life aspects in affected individuals.

Role of C-C chemokine receptor type 5 in pathogenesis of malaria and its severe forms.

Malaria is a mosquito-borne disease caused by Plasmodium parasites, responsible for a significant impact on public health in several tropical and sub-tropical countries. The majority of infection cases are classified as uncomplicated malaria, causing mild symptoms such as fever and headache. However, the disease may progress to severe malaria and death if the infection is not properly treated. Furthermore, malaria poses a major concern for children, pregnant women and immunosuppressed individuals. Exacerbated inflammation is characteristic of severe malaria cases. The C-C chemokine receptor type 5 (CCR5) is an important molecule for leukocyte migration and regulation of inflammation. Although widely known as an HIV-1 co-receptor, CCR5 also affects the susceptibility and progression of autoimmune and inflammatory diseases. There is evidence supporting the participation of CCR5 in malaria manifestations, with the evaluation of CCR5 gene expression levels suggested as a marker to monitor malaria severity. Certain genetic variants in the CCR5 gene affect CCR5 expression, potentially altering CCR5-mediated inflammatory responses during malaria infection. However, the complex influences of CCR5 on malaria remain underexplored. Therefore, this review examines and updates the role of CCR5 in various contexts of malaria infection, including uncomplicated malaria, Plasmodium/HIV co-infection, pregnancy and severe (cerebral) malaria.

Gut microbiome-derived metabolites in Alzheimer's disease: Regulation of immunity and potential for therapeutics.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and cause of dementia. Despite the prevalence of AD, there is a lack of effective disease modifying therapies. Recent evidence indicates that the gut microbiome (GMB) may play a role in AD through its regulation of innate and adaptive immunity. Gut microbes regulate physiology through their production of metabolites and byproducts. Microbial metabolites may be beneficial or detrimental to the pathogenesis and progression of inflammatory diseases. A better understanding of the role GMB-derived metabolites play in AD may lead to the development of therapeutic strategies for AD. In this review, we summarize the function of bioactive GMB-derived metabolites and byproducts and their roles in AD models. We also call for more focus on this area in the gut-brain axis field in order to create effective therapies for AD.

Bronchiectasis Exacerbations: Are We Doing Everything We Can?

At the European Respiratory Society (ERS) Congress 2024, two experts in bronchiectasis, Pieter Goeminne, Department of Respiratory Diseases, Vitaz Saint-Nicholas Hospitals, Belgium, and Michal Shteinberg, Pulmonology Institute and CF Center – Carmel Medical Center; Israel Institute of Technology; and The B. Rappaport Faculty of Medicine, Haifa, Israel, discussed bronchiectasis’ pathogenesis and exacerbations, along with unmet needs regarding diagnosis and treatment. Bronchiectasis is a chronic and progressive inflammatory disease with a rising prevalence. Commonly associated conditions/related comorbidities of bronchiectasis include post-infective diseases and other airway conditions (such as chronic obstructive pulmonary disease [COPD] and asthma), although the cause of bronchiectasis may remain unknown in over a third of patients. Development of bronchiectasis involves the intersection of four pathogenic components: chronic infections, airway ciliary dysfunction, chronic inflammation (mostly neutrophilic), and structural lung damage, commonly known as the ‘vicious vortex.’ In particular, bronchiectasis development, progression, and exacerbation also involve upregulated and dysregulated neutrophil function. Exacerbations in bronchiectasis are marked by symptoms of increased cough, sputum changes, decreased lung function, and fatigue, among others. Careful clinical examination and awareness of bronchiectasis symptoms are needed to properly diagnose and treat the initial condition and prevent exacerbations. Triggers for exacerbations can be endogenous, such as neutrophil or eosinophil increases, as well as exogenous, including the presence of infectious agents and pollution. Research regarding treatment for bronchiectasis is limited, but European guidelines recommend airway clearance techniques and antibiotics during exacerbations. To enable more targeted treatment for bronchiectasis from first occurrence, to limit exacerbations, and during an exacerbation, there are unmet needs for better identification of resistant genes, treatments for pathogens and inflammation, and biomarkers of exacerbation triggers.

MiR-1307-5p enhances fibroblast transdifferentiation to exacerbate chronic obstructive pulmonary disease through regulating FBXL16/HIF1α axis

Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients. Mechanistically, we found that upregulation of miR-1307-5p promoted TGF-β induced lung fibroblast activation and transdifferentiation. We also identified FBXL16 as a direct target for miR-1307-5p mediated myofibroblast activation in COPD. Knockdown of FBXL16 by siRNA prominently increased the expression of myofibroblast markers in MRC-5 fibroblasts after TGF-β administration. Ectopic expression of FBXL16 in MRC-5 counteracted miR-1307-5p agomir-induced fibroblast transdifferentiation. Furthermore, We found that miR-1307-5p promoted pulmonary fibroblast transdifferentiation through FBXL16 regulated HIF1α degradation. In general, our findings indicate that miR-1307-5p is important for COPD pathogenesis, and may serve as a potential target for COPD treatment.

Anti-Inflammatory Potential of Costus speciosus rhizome Bioactive Phytochemicals: A Combined GC-MS and Computational Approach Targeting TLR-4 Signaling.

Plants represent a rich reservoir of bioactive compounds with established therapeutic value in diverse diseases. Notably, the Toll-like receptor-4 (TLR-4) signaling pathway plays a pivotal role in inflammation. Upon engagement with pro-inflammatory ligands like lipopolysaccharide, TLR-4 triggers downstream cascades involving nuclear factor ĸappa B and mitogen- activated protein kinases. This signaling cascade ultimately dictates the onset and progression of inflammatory diseases. Therefore, targeting TLR-4 signaling offers a promising therapeutic approach for managing inflammatory disorders. This study investigated the potential of Costus speciosus rhizome phytocompounds, a traditional medicinal plant, as novel as modulators of TLR-4 signaling, highlighting their mechanisms of action and potential clinical applications. In the present study, 18 phytocompounds isolated from the rhizome of Costus speciosus, were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. The compounds exhibited binding affinities ranging from -4.087 to -8.93 kcal/mol with the TLR-4 protein due to the formation of multiple intermolecular interactions. Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, methyl ester (compound 7) exhibited exceptional binding energy (-8.93 kcal/mol), indicating strong affinity for the TLR-4 protein. Additionally, compound 7 displayed favorable ADMET properties, suggesting promising drug development potential. Molecular dynamics simulations confirmed the stability of the compound 7-TLR4 complex, further supporting its ability to modulate TLR-4 signaling. These findings highlight the therapeutic potential of Costus speciosus phytocompounds, particularly compound 7, as potent anti-inflammatory modulators. Further research is warranted to validate their anti-inflammatory and neuroprotective effects in pre-clinical models, paving the way for their development as novel therapeutic agents for inflammatory diseases.

Identification of novel proteins in inflammatory bowel disease based on the gut-brain axis: a multi-omics integrated analysis

BackgroundThe gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear.Materials and methodsIn this study, we aimed to investigate “novel proteins” underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn’s disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes.ResultsPWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD.ConclusionThe two “novel proteins,” SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

Mechanisms of Lung Endothelial Cell Injury and Survival in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, chronic, and incurable inflammatory pulmonary vascular disease characterized by significant sex bias and largely unexplored microbial-associated molecular mechanisms that may influence its development and sex prevalence across various subgroups. PAH can be subclassified as idiopathic, heritable, or associated with conditions such as connective tissue diseases, congenital heart defects, liver disease, infections, and chronic exposure to drugs or toxins. During PAH progression, lung vascular endothelial cells (ECs) undergo dramatic morphofunctional transformations in response to acute and chronic inflammation. These transformations include the appearance and expansion of abnormal vascular cell phenotypes such as those derived from apoptosis-resistant cell growth and endothelial-to-mesenchymal transition (EndoMT). Compelling evidence indicates that these endothelial phenotypes seem to be triggered by chronic lung vascular injury and dysfunction, often characterized by reduced secretion of vasoactive molecules like nitric oxide (NO) and exacerbated response to vasoconstrictors such as Endothelin-1 (ET-1); both long-term known contributors of PAH pathogenesis. This review sheds light on the mechanisms of EC dysfunction, apoptosis, and EndoMT in PAH, aiming to unravel the intricate interactions between ECs, pathogens, and other cell types that drive the onset and progression of this devastating disease. Ultimately, we hope to provide an overview of the complex functions of lung vascular ECs in PAH, inspiring novel therapeutic strategies that target these dysfunctional cells to improve the treatment landscape for PAH, particularly in the face of current and emerging global pathogenic threats.

EF24, a Curcumin Analog, Reverses Interleukin-18-Induced miR-30a or miR-342-Dependent TRAF3IP2 Expression, RECK Suppression, and the Proinflammatory Phenotype of Human Aortic Smooth Muscle Cells.

Curcumin, a polyphenolic compound derived from the widely used spice Curcuma longa, has shown anti-atherosclerotic effects in animal models and cultured vascular cells. Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells. Here we hypothesized that EF24, a curcumin analog with a better bioavailability and bioactivity profile, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). The exposure of ASMC to functionally active recombinant human IL-18 (10 ng/mL) upregulated TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 inhibited both miR-30a and miR-342 in a p38 MAPK- and JNK-dependent manner, and while miR-30a mimic blunted IL-18-induced TRAF3IP2 expression, miR-342 mimic restored RECK expression. Further, IL-18 induced ASMC migration, proliferation and proinflammatory phenotype switching, and these effects were attenuated by TRAF3IP2 silencing, and the forced expression of RECK or EF24. Together, these results suggest that the curcumin analog EF24, either alone or as an adjunctive therapy, has the potential to delay the development and progression of atherosclerosis and other vascular inflammatory and proliferative diseases by differentially regulating TRAF3IP2 and RECK expression in ASMC.

Insights of Expression Profile of Chemokine Family in Inflammatory Bowel Diseases and Carcinogenesis

Chemokines are integral components of the immune system and deeply involved in the pathogenesis and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although a considerable amount of transcriptome data has been accumulated on these diseases, most of them are limited to a specific stage of the disease. The purpose of this study is to visually demonstrate the dynamic changes in chemokines across various stages of bowel diseases by integrating relevant datasets. Integrating the existing datasets for IBD and CRC, we compare the expression changes of chemokines across different pathological stages. This study collected 11 clinical databases from various medical centers around the world. Patients: Data of patient tissue types were classified into IBD, colorectal adenoma, primary carcinoma, metastasis, and healthy control according to the publisher’s annotation. The expression changes in chemokines in various pathological stages are statistically analyzed. The chemokines were clustered by different expression patterns. The chemokine family was clustered into four distinct expression patterns, which correspond to varying expression changes in different stages of colitis and tumor development. Certain chemokines and receptors associated with inflammation and tumorigenesis have been identified. Furthermore, it was confirmed that the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model and the azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colon cancer model shows stronger correlations with the clinical data in terms of chemokine expression levels. This study paints a panoramic picture of the expression profiles of chemokine families at multiple stages from IBD to advanced colon cancer, facilitating a comprehensive understanding of the regulation patterns of chemokines and guiding the direction of drug development. This study provides researchers with a clear atlas of chemokine expression in the pathological processes of inflammatory bowel disease and colon cancer.

Causal effects of plasma metabolites on autoimmune hepatitis (AIH): a bidirectional two-sample mendelian randomization study

Autoimmune hepatitis(AIH) is a chronic progressive inflammatory liver disease induced by loss of immune tolerance. The role of circulating metabolites in disease pathogenesis is unclear. This study aimed to investigate potential causal links between plasma metabolites and AIH risk by employing a two-sample Mendelian randomization approach. A comprehensive bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide significant variant-metabolite and variant-AIH associations in European ancestry individuals. Various methods assessed causal relationships among 1400 metabolites and AIH, incorporating sensitivity analyses to evaluate pleiotropy and heterogeneity. Fifty-eight metabolites displayed possible associations, including increased AIH risk with genetically predicted higher kynurenine (p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07) and a protective effect for the dopamine sulfate ratio (p = 1.06 × 10− 5,OR: 0.62, 95% CI 0.49–0.79). Reciprocal analysis revealed a causal effect of AIH on kynurenine( p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07), but not on the dopamine sulfate ratio(p = 0.691, OR: 1.05, 95% CI 0.67–1.64). Our genetics-based approach provides evidence supporting a causal role for specific metabolite levels in AIH risk. The results deliver evidence supporting a causal effect of a specific metabolite ratio(dopamine 4-sulfate/dopamine 3-O-sulfate) on AIH risk. Experimental validation and mechanistic examinations are warranted to confirm findings.

TIPE2 aggravates experimental colitis and disrupts intestinal epithelial barrier integrity by activating JAK2/STAT3/SOCS3 signal pathway

Ulcerative colitis (UC) is a chronic relapsing and progressive inflammatory disease of the colon. TIPE2 is a negative regulator of innate and adaptive immunity that maintains immune homeostasis. We found that TIPE2 was highly expressed in mucosa of mice with colitis. However, the role of TIPE2 in colitis remains unclear. We induced colitis in mice with dextran sulphate sodium (DSS) and treated them with TIPE2, and investigated the inflammatory activity of the colon in vivo by cytokines detection and histopathological analyses. We also measured inflammatory alteration and tight junctions induced by DSS in vitro. The results demonstrated that administration of TIPE2 promoted the severity of colitis in mice and human colon epithelial cells. Furthermore, TIPE2 aggravated intestinal epithelial barrier dysfunction by decreasing the expression of the tight junction proteins Occludin, Claudin-1 and ZO-1. In addition, TIPE2 exacerbated intestinal inflammatory response by inhibiting the expression of SOCS3, remarkably activating JAK2/STAT3 signaling pathway, and increasing the translocation of phosphorylated STAT3 into the nucleus. Silencing of Tipe2 attenuated the DSS-induced activation of JAK2/STAT3, thereby rescuing epithelial inflammatory injury and restoring barrier dysfunction. These results indicate that TIPE2 augments experimental colitis and disrupted the integrity of the intestinal epithelial barrier by activating the JAK2/STAT3/SOCS3 signaling pathway.

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.

Intralesional gene expression profile of JAK-STAT signaling pathway and associated cytokines in Leishmania tropica-infected patients.

The JAK-STAT signaling pathway is a central cascade of signal transduction for the myriad of cytokines in which dysregulation has been implicated in progression of inflammatory and infectious diseases. However, the involvement of this pathway in human cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica warrants further investigation. This study sought to investigate differential gene expression of several cytokines and their associated jak-stat genes in the lesions of L. tropica-infected patients byquantitative Real-Time PCR. Further, the expression of five inhibitory immune checkpoint genes was evaluated. Results showed that the gene expression levelsof both Th1 (ifng, il12, il23) and Th2 (il4, il10) types cytokines were increased in the lesion of studied patients. Further, elevated expression levels of il35, il21, il27 and il24 genes were detected in the lesions of CL patients. Notably, the expression of the majority of genes involved in JAK/STAT signaling pathway as well as checkpoint genes including pdl1, ctla4 and their corresponding receptors was increased. Our finding revealed dysregulation of cytokines and related jak-stat genes in the lesion of CL patients. These results highlight the need for further exploration of the functional importance of these genes in the pathogenesis of, and immunity to, CL.

THE IMMUNOMODULATORY ROLE OF CYTOKINES IN THE PATHOGENESIS OF PERIODONTAL DISEASE

Background:Inflammatory periodontal diseases are one of the most acute problems of modern dentistry, which is associated with their widespread prevalence in the world. In the structure of periodontal diseases, periodontitis a leading place in the age group of 40-50 years. Many factors play a role in the etiology of periodontitis, the most important of which are the local microbiota and the host immune response. Cytokines play an extremely important role. Cytokines are key modulators of both homeostasis and inflammatory processes, acting in the first wave of responses against pathogens, stimuli at barrier sites and linking tissue cells to lymphocytes and additional cell populations. Objective:The aim of the study was to analyze modern literature on the role of cytokines in the etiology and pathogenesis of inflammatory periodontal diseases. Materials and methods:Data Extraction: A comprehensive electronic literature search was performed in the following databases:PubMed, Scopus,Web of Scienc, Google Scholar, EBSCO host from 2000 to 2024 terms: periodontitis, infection, inflammation, immunity, cytokines, interleukin. 124 articles were found and 50 full-text articles of high methodological quality were selected according to the review method used, the PRISMA. Inclusion criteria:included clinical trials, considered randomized controlled trials, cross-sectional studies, casecontrol studies, and cohort studies in human subjects that evaluated the current literature on the periodontitis, infection, inflammation, immunity, cytokines, interleukin written in English articles.There was no limitation on minimal quality, minimal sample size, or the number of patients. Exclusion criteria were:original primary studies, due to language limitations , abstracts, letters to the editor, book chapters, case reports, conference abstracts, duplicate publications, and in vitro and in vivo animal experimental studies. Result:Many factors of general and local origin are involved in the development and progression of inflammatory periodontal diseases. Microorganisms and their products cause activation of the host immune system, which results in the release of cytokines and other proinflammatory biomarkers that cause tissue damage. The inflammatory process in periodontal tissues progresses through various stages, beginning with the infiltration of immune cells into the gingival tissue. Immune cells secrete proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α),which further promote inflammation and tissue destruction. The interaction between bacterial biofilm and the immune response, which is mainly controlled by cytokines, determines the course of periodontal disease. Conclusion:The etiology and pathogenesis of periodontal disease is quite complex, diverse and not yet fully disclosed. Cytokines are control and modulate the immune response in periodontitis

Orally Deliverable Microalgal-Based Carrier with Selenium Nanozymes for Alleviation of Inflammatory Bowel Disease.

Excessive reactive oxygen species (ROS) is a hallmark of both the onset and progression of inflammatory bowel disease (IBD), where a continuous cycle of ROS and inflammation drives the progression of diseases. The design of oral antioxidant nanoenzymes for scavenging ROS has emerged as a promising strategy to intervene in IBD. However, the practical application of these nanoenzymes is limited due to their single catalytical property and significantly impacted by substantial leakage in the upper gastrointestinal tract. This study introduces a novel oral delivery system, SP@CS-SeNPs, combining natural microalgae Spirulina platensis (SP), which possesses superoxide dismutase (SOD)-like activity, with chitosan-functionalized selenium nanoparticles (CS-SeNPs) that exhibit catalase-like activity. The SP@CS-SeNPs system leverages the dual catalytic capabilities of these components to initiate a cascade reaction that first converts superoxide anion radicals (O2•-) into hydrogen peroxide (H2O2), and then catalyzes the decomposition of H2O2 into water and oxygen. This system not only utilizes the resistance of the microalgae carrier to gastric acid and its efficient capture by intestinal villi, thereby enhancing intestinal distribution and retention but also demonstrates significant anti-inflammatory effects and effective repair of the damaged intestinal barrier in a colitis mice model. These results demonstrate that this oral delivery system successfully combines the features of microalgae and nanozymes, exhibits excellent biocompatibility, and offers a novel approach for antioxidant nanozyme intervention in IBD.

Potential Application of Plant-Derived Compounds in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration, resulting in significant disability and reduced quality of life. Current therapeutic strategies primarily target immune dysregulation, but limitations in efficacy and tolerability highlight the need for alternative treatments. Plant-derived compounds, including alkaloids, phenylpropanoids, and terpenoids, have demonstrated anti-inflammatory effects in both preclinical and clinical studies. By modulating immune responses and promoting neuroregeneration, these compounds offer potential as novel adjunctive therapies for MS. This review provides insights into the molecular and cellular basis of MS pathogenesis, emphasizing the role of inflammation in disease progression. It critically evaluates emerging evidence supporting the use of plant-derived compounds to attenuate inflammation and MS symptomology. In addition, we provide a comprehensive source of information detailing the known mechanisms of action and assessing the clinical potential of plant-derived compounds in the context of MS pathogenesis, with a focus on their anti-inflammatory and neuroprotective properties.

A Novel Microbial Dysbiosis Index and Intestinal Microbiota-Associated Markers as Tools of Precision Medicine in Inflammatory Bowel Disease Paediatric Patients.

Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium, Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.

Evaluation of platelet indices in chronic kidney disease

Objective: Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney functions and accumulation of uremic toxins in the body. Platelet indices have the potential to predict the inflammatory status and disease progression in patients with CKD. In this study it was aimed to investigate platelet indices and their relations with renal function and comorbid conditions in CKD patients. Method: In this study it was included 411 CKD patients. We looked for associations between platelet indices and estimated glomerular filtration rate (eGFR). We generated linear regression models for platelet indices that may be associated with eGFR. We evaluated CKD patients for possible associations between platelet indices and comorbid conditions such as diabetes, hypertension, and cardiovascular diseases. Results: The mean age of CKD patients was 60.5 and the GFR value was 40.1+24.8 mL/min/1.73m2. While the mean platelet count, MPV, PCT, PDW, P-LCR values were lower in the advanced CKD group, hematocrit adjusted platelet count (HAPC), MPV/Lymphocyte ratio and SII parameters were higher in the advanced CKD group (p