Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions—2nd Edition

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 14406

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Guest Editor
Department of Biophysics, Medical University of Białystok, Mickiewicza 2a, 15-089 Białystok, Poland
Interests: interleukin; injury; markers of inflammatory response; metalloproteinases; protein DAMPs; proteasome; wound healing process; tissue damage
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Guest Editor
Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland
Interests: cancer; central nervous system diseases; cerebrospinal fluid; cytokines; biomarker; inflammation markers
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Guest Editor

Special Issue Information

Dear Colleagues,

The Guest Editors are grateful to the many researchers who contributed to the success of the first volume of this Special Issue (https://www.mdpi.com/journal/life/special_issues/Z1374P2U2X). We are very pleased to announce the second volume of our Special Issue, entitled “Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions—2nd Edition”.

Inflammation is a complex and necessary component of the response to pathological conditions, such as infections, burns, stress, trauma, or immunologic reactions. Inflammation has been linked to numerous diseases, including arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, and cancer, as well as to conditions associated with aging. Inflammatory responses involve the release of various inflammatory markers. The evaluation of biomarkers such as cytokines, growth factors, oxidative markers, and other molecular markers allows us to understand the progression of various disorders and tissue repair processes. Monitoring the levels of inflammatory markers in body fluids may be useful for diagnosing inflammation as well as monitoring disease treatment. The most frequently used inflammatory markers include acute-phase proteins and cytokines, predominantly TNF-α, interleukins 1β, 6, 8, 10, and 12, their receptors, and IFNγ. However, new inflammatory response and tissue damage markers that can provide valuable information about various pathological conditions are still being sought.

In this Special Issue, all articles, including original papers, reviews, and other forms of scientific communication, that present valuable observations concerning common and novel markers of inflammation and tissue damage in various pathological conditions are welcome.

Dr. Marzena Tylicka
Dr. Joanna Kamińska
Dr. Olga Koper-Lenkiewicz
Guest Editors

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Keywords

  • body fluids
  • cytokines
  • damage-associated molecular patterns (DAMPs)
  • inflammatory response
  • injury
  • markers of inflammation and tissue damage
  • metalloproteinases
  • novel markers
  • pathological conditions
  • proteasome
  • tissue damage
  • tissue repair processes
  • various diseases

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Published Papers (8 papers)

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Research

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15 pages, 2604 KB  
Article
“Protective” Imazalil vs Its Negative Effects on Immune System Cells—Neutrophils
by Wioletta Ratajczak-Wrona, Aleksandra Aniszewska, Agnieszka Iwaniuk, Marzena Garley, Sławomir Wołczyński, Dariusz Jan Skarżynski, Jolanta Wrobel, Agnieszka Zebrowska, Piotr Radziwon, Barbara Pucelik and Ewa Jabłońska
Life 2026, 16(2), 365; https://doi.org/10.3390/life16020365 - 23 Feb 2026
Cited by 1 | Viewed by 584
Abstract
Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as [...] Read more.
Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as the commonly used imazalil (IMZ) constitute a significant group. The objective of this study was to assess the effect of IMZ (at an environmental dose of 0.07 ng/mL, as well as 10- and 100-fold higher doses) on selected functions of neutrophils. This study demonstrated that neutrophils incubated with IMZ at a dose detectable in the serum, exhibited lower phagocytotic capacity. In addition, at a 10-fold higher dose, this compound reduced the chemotactic capacity of neutrophils and led to increased activity of NADPH oxidase in these cells. Furthermore, it was observed that at the highest concentration used in this study IMZ intensified the production of nitric oxide. The exposure of neutrophils—the first line of defense—to IMZ affected their locomotion and pathogen-eliminating function. Moreover, the response of neutrophils was not proportionate to the concentration of IMZ used in the study. Full article
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16 pages, 653 KB  
Article
Diagnostic Value of Mean Platelet Volume and Hematological Inflammatory Ratios in Brucellosis: A Case–Control Study
by Enes Dalmanoğlu, Yeşim Çağlar and Gülce Eylül Aldemir
Life 2026, 16(2), 352; https://doi.org/10.3390/life16020352 - 18 Feb 2026
Viewed by 726
Abstract
Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital [...] Read more.
Brucellosis diagnosis remains challenging in resource-limited endemic settings. This retrospective case–control study evaluated the diagnostic utility of mean platelet volume (MPV) and hematological inflammatory ratios in brucellosis. Fifty patients with confirmed brucellosis and 50 age-matched healthy controls were included at a university hospital in Turkey (2015–2018). Complete blood count parameters, hematological ratios (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured at diagnosis. Receiver operating characteristic (ROC) curve analysis evaluated diagnostic performance; multivariate logistic regression developed a combined model. Brucellosis patients showed significantly lower MPV (8.04 ± 0.95 vs. 8.56 ± 0.69 fL, p = 0.002), higher platelet counts (305.0 ± 116.0 vs. 246.0 ± 55.2 × 103/μL, p = 0.002), lower NLR (median: 1.69 vs. 2.07, p = 0.013), and higher LMR (median: 5.28 vs. 4.12, p = 0.008). ESR demonstrated the best individual diagnostic performance (area under the curve [AUC] = 0.842). The combined model (MPV + ESR + CRP) achieved superior performance (AUC = 0.891, sensitivity 84%, specificity 86%). Limitations include the single-center retrospective design, lack of internal validation, and comparison with healthy controls only. Notably, healthy controls were deliberately selected to establish baseline hematological profiles associated with brucellosis rather than to differentiate it from other infections. Brucellosis presents a unique hematological profile with decreased MPV and altered inflammatory ratios. The combined model offers a potentially cost-effective screening approach for endemic settings, pending external validation. Full article
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13 pages, 224 KB  
Article
Personalized Supplementation Is Associated with Reduced Inflammatory Biomarkers: A 12-Week Observational Study
by Eliza Roeth, Madeline Morris, Asher P. Reynolds, Emma M. Reynolds, Reed Hungerford, Eliza J. Livingston, Andrew W. Richardson, Benjamin T. Bikman and Paul R. Reynolds
Life 2025, 15(12), 1887; https://doi.org/10.3390/life15121887 - 10 Dec 2025
Cited by 1 | Viewed by 2422
Abstract
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring [...] Read more.
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article
13 pages, 253 KB  
Article
Evaluation of Total Homocysteine Levels in Relation to Abdominal Fat Mass and Traditional Cardiovascular Risk Factors in Overweight and Obese Adolescents
by Małgorzata Rumińska, Ewelina Witkowska-Sędek, Maria Krajewska, Anna Stelmaszczyk-Emmel, Maria Sobol and Beata Pyrżak
Life 2025, 15(8), 1329; https://doi.org/10.3390/life15081329 - 21 Aug 2025
Cited by 2 | Viewed by 1609
Abstract
Cardiovascular diseases remain the leading cause of mortality worldwide, with multiple risk factors contributing to their development. Among these, obesity and hyperhomocysteinemia have been recognized as significant contributors to endothelial dysfunction, a key early event in the pathogenesis of atherosclerosis. Our study aimed [...] Read more.
Cardiovascular diseases remain the leading cause of mortality worldwide, with multiple risk factors contributing to their development. Among these, obesity and hyperhomocysteinemia have been recognized as significant contributors to endothelial dysfunction, a key early event in the pathogenesis of atherosclerosis. Our study aimed to evaluate the relationship between total homocysteine (tHcy) levels and traditional cardiovascular risk factors in overweight and obese adolescents. We enrolled 42 obese, 14 overweight, and 25 non-obese children. No significant differences in tHcy levels were observed between overweight, obese, and non-obese adolescents. Homocysteine positively correlated with age (r = 0.433, p < 0.011) and creatinine concentrations (r = 0.363, p = 0.001) in the overall group of overweight, obese, and non-obese children, as well as in the combined group of overweight and obese children (for age: r = 0.275, p = 0.025; for creatinine: r = 0.278, p = 0.025). We did not find any association between homocysteine and atherogenic lipid profile, insulin-resistance status, blood pressure, and inflammatory parameters in overweight and obese patients. Age emerged as the strongest independent predictor of homocysteine levels. The observed association with creatine suggests a potential renal contribution to homocysteine metabolism. Full article
16 pages, 1691 KB  
Article
Predictive Biomarkers of Acute Kidney Injury in COVID-19: Distinct Inflammatory Pathways in Patients with and Without Pre-Existing Chronic Kidney Disease
by Caterina Carollo, Alida Benfante, Alessandra Sorce, Katia Montalbano, Emanuele Cirafici, Leonardo Calandra, Giulio Geraci, Giuseppe Mulè and Nicola Scichilone
Life 2025, 15(5), 720; https://doi.org/10.3390/life15050720 - 29 Apr 2025
Cited by 3 | Viewed by 1604
Abstract
Background: Acute kidney injury (AKI) has emerged as a significant complication in patients with coronavirus disease 2019 (COVID-19). The pathophysiology of COVID-19-associated AKI is multifactorial, involving both direct viral effects on renal cells and indirect mechanisms such as systemic inflammation and cytokine storms. [...] Read more.
Background: Acute kidney injury (AKI) has emerged as a significant complication in patients with coronavirus disease 2019 (COVID-19). The pathophysiology of COVID-19-associated AKI is multifactorial, involving both direct viral effects on renal cells and indirect mechanisms such as systemic inflammation and cytokine storms. This highlights the critical need for early detection and effective management strategies to mitigate kidney injury and improve patient outcomes. The aim of our study is to assess the potential predictive role of inflammatory biomarkers in determining the risk of developing COVID-19-associated AKI in patients with and without pre-existing CKD. Methods: This study included 84 patients stratified by pre-existing chronic kidney disease (CKD) status. Demographic, clinical, and laboratory data were collected, including vital signs, hematological profiles, renal function markers, inflammatory biomarkers, coagulation parameters, and treatments. Outcomes such as acute kidney injury (AKI) and in-hospital mortality were documented. Results: In patients with pre-existing CKD, IL-6 and NLR demonstrated high predictive accuracy for AKI onset. In patients without pre-existing CKD, white blood cell (WBC) count emerged as a significant predictor of AKI onset. Conclusions: The differential roles of IL-6, NLR, and WBC in predicting AKI onset highlight distinct physiopathological pathways influenced by COVID-19. In CKD+ patients, chronic inflammation and immune dysregulation are key drivers of AKI, with IL-6 and NLR serving as robust markers of this inflammatory state. In contrast, in CKD− patients, AKI may be more influenced by acute inflammatory responses and infectious factors, as reflected by WBC count. Full article
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Review

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29 pages, 1228 KB  
Review
A Narrative Review on Abnormalities in the Hemostatic System in Diabetes Mellitus: Pathophysiology, Clinical Implications, and Therapeutics
by Sana Rafaqat, Hafsa Hamid, Fakhra Bashir, Hijab Abaid, Aleksandra Klisic, Saira Rafaqat and Filiz Mercantepe
Life 2026, 16(4), 648; https://doi.org/10.3390/life16040648 - 12 Apr 2026
Viewed by 730
Abstract
Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation [...] Read more.
Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article
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31 pages, 2937 KB  
Review
Intersecting Pathways of Inflammation, Oxidative Stress, and Atherogenesis in the Evaluation of CKD: Emerging Biomarkers PCSK9, EPHX2, AOPPs, and TBARSs
by Mohamed-Zakaria Assani, Marius Bogdan Novac, Anda Lorena Dijmărescu, Alexandra-Ștefania Stroe-Ionescu, Mihail Virgil Boldeanu, Isabela Siloși and Lidia Boldeanu
Life 2025, 15(8), 1287; https://doi.org/10.3390/life15081287 - 13 Aug 2025
Cited by 4 | Viewed by 2764
Abstract
Chronic kidney disease (CKD) is a multifactorial disorder increasingly recognized as a systemic condition marked by persistent inflammation, oxidative stress, dyslipidemia, and endothelial dysfunction. Diabetic nephropathy, a leading cause of CKD, amplifies cardiovascular risk through intertwined mechanisms beyond traditional risk factors. This review [...] Read more.
Chronic kidney disease (CKD) is a multifactorial disorder increasingly recognized as a systemic condition marked by persistent inflammation, oxidative stress, dyslipidemia, and endothelial dysfunction. Diabetic nephropathy, a leading cause of CKD, amplifies cardiovascular risk through intertwined mechanisms beyond traditional risk factors. This review synthesizes current evidence on the interplay between inflammation, oxidative stress, and atherosclerosis in CKD, with a special focus on emerging molecular biomarkers—PCSK9, EPHX2, AOPPs, and TBARSs—and their integration with clinical indices. These markers illuminate pathophysiological networks underlying CKD progression and cardiovascular complications, offering novel insights into risk stratification, disease monitoring, and targeted therapy. By exploring molecular and clinical intersections, this review underscores the potential of a personalized, biomarker-driven approach to CKD management. Full article
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Other

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14 pages, 863 KB  
Systematic Review
Effects of Vitamin D3 Supplementation on Inflammatory Markers in Overweight and Obese Children and Adolescents: A Systematic Review
by Maria Krajewska and Ewelina Witkowska-Sędek
Life 2025, 15(7), 1142; https://doi.org/10.3390/life15071142 - 20 Jul 2025
Cited by 2 | Viewed by 2716
Abstract
Obesity-related low-grade inflammation is a significant factor responsible for the development of metabolic syndrome and chronic diseases, which can begin even in early childhood. Recently, there has been growing interest in the impact of vitamin D3 supplementation on inflammatory markers in overweight and [...] Read more.
Obesity-related low-grade inflammation is a significant factor responsible for the development of metabolic syndrome and chronic diseases, which can begin even in early childhood. Recently, there has been growing interest in the impact of vitamin D3 supplementation on inflammatory markers in overweight and obese individuals; however, findings remain inconsistent. Therefore, we aimed to conduct a systematic review to assess the effects of vitamin D3 supplementation on inflammatory markers in overweight and obese children and adolescents, focused exclusively on the analysis of randomized controlled trials (RCTs) identified by searching PubMed, EMBASE, and Cochrane Library. The results of this study were synthesized and reported following the PRISMA statement. A total of 294 citations were identified through electronic literature searches, of which two RCTs were finally included in our systematic review. We found that vitamin D3 supplementation did not affect the changes in C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), but led to a decrease in leptin levels. The small number of studies meeting the inclusion criteria for our systematic review limits the value of the presented results, but also indicates the need for in-depth research on this topic. Full article
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