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Search Results (188)

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Keywords = immunological index

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25 pages, 4837 KiB  
Article
Multimodal Computational Approach for Forecasting Cardiovascular Aging Based on Immune and Clinical–Biochemical Parameters
by Madina Suleimenova, Kuat Abzaliyev, Ainur Manapova, Madina Mansurova, Symbat Abzaliyeva, Saule Doskozhayeva, Akbota Bugibayeva, Almagul Kurmanova, Diana Sundetova, Merey Abdykassymova and Ulzhas Sagalbayeva
Diagnostics 2025, 15(15), 1903; https://doi.org/10.3390/diagnostics15151903 - 29 Jul 2025
Viewed by 189
Abstract
Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, [...] Read more.
Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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16 pages, 957 KiB  
Article
The Influence of Blood Transfusion Indexed to Patient Blood Volume on 5-Year Mortality After Coronary Artery Bypass Grafting—An EuroSCORE II Adjusted Spline Regression Analysis
by Joseph Kletzer, Maximilian Kreibich, Martin Czerny, Tim Berger, Albi Fagu, Laurin Micek, Ulrich Franke, Matthias Eschenhagen, Tau S. Hartikainen, Mirjam Wild and Dalibor Bockelmann
J. Cardiovasc. Dev. Dis. 2025, 12(8), 287; https://doi.org/10.3390/jcdd12080287 - 28 Jul 2025
Viewed by 302
Abstract
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: [...] Read more.
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: We retrospectively analyzed 3376 patients undergoing isolated CABG between 2005 and 2023 at a single tertiary center. Patients who died during their perioperative hospital stay within 30 days were excluded. Transfusion burden was assessed both as the absolute number of blood product units (packed red blood cells, platelet transfusion, fresh frozen plasma) and as a percentage of calculated patient blood volume. The primary outcome was all-cause mortality at 5 years. Flexible Cox regression with penalized smoothing splines, adjusted for EuroSCORE II, was used to model dose–response relationships. Results: From our cohort of 3376 patients, a total of 137 patients (4.05%) received >10 units of packed red blood cells (PRBC) perioperatively. These patients were older (median 71 vs. 68 years, p < 0.001), more often female (29% vs. 15%, p < 0.001), and had higher preoperative risk (EuroSCORE II: 2.53 vs. 1.41, p < 0.001). After 5 years, mortality was 42% in the massive transfusion group versus 10% in controls. Spline regression revealed an exponential increase in mortality with transfused units: 14 units yielded a 1.5-fold higher hazard of death (HR 1.46, 95% CI 1.31–1.64), rising to HR 2.71 (95% CI 2.12–3.47) at 30 units. When transfusion was indexed to blood volume, this relationship became linear and more tightly correlated with mortality, with lower maximum hazard ratios and narrower confidence intervals. Conclusions: Indexing transfusion burden to the percentage of patient blood volume replaced provides a more accurate and clinically actionable predictor of 5-year mortality after CABG than absolute unit counts. Our findings support a shift toward individualized, volume-based transfusion strategies to optimize patient outcomes and resource stewardship in a time of limited availability of blood products. Full article
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20 pages, 311 KiB  
Article
Serum Concentrations of Vascular Endothelial Growth Factor in Polish Patients with Systemic Lupus Erythematosus Are Associated with Cardiovascular Risk and Autoantibody Profiles
by Katarzyna Fischer, Hanna Przepiera-Będzak, Marcin Sawicki, Maciej Brzosko and Marek Brzosko
J. Clin. Med. 2025, 14(14), 5133; https://doi.org/10.3390/jcm14145133 - 19 Jul 2025
Viewed by 409
Abstract
Background/Objectives: This study was conducted to analyze the associations between vascular endothelial growth factor (VEGF) serum concentrations and immunological biomarkers, inflammatory parameters, classical atherosclerosis risk factors, and cardiovascular manifestations in systemic lupus erythematosus (SLE) patients. Methods: The project included 83 individuals [...] Read more.
Background/Objectives: This study was conducted to analyze the associations between vascular endothelial growth factor (VEGF) serum concentrations and immunological biomarkers, inflammatory parameters, classical atherosclerosis risk factors, and cardiovascular manifestations in systemic lupus erythematosus (SLE) patients. Methods: The project included 83 individuals suffering from SLE, with 20 healthy individuals as controls. The serum levels of VEGF were determined through the ELISA method using R&D Systems tests. Laboratory markers, autoantibody profiles, traditional atherosclerotic risk factors, and organ manifestations were evaluated. Atherosclerotic changes were determined based on several indices including carotid intima-media thickness, ankle-brachial index and high resistance index assessments. Results: The reference range of serum VEGF concentrations was established based on the 25th and 75th percentiles obtained in the controls. High VEGF levels were significantly correlated with the presence of selected anti-phospholipid antibodies such as anti-prothrombin (OR = 10.7; 95%CI: 2.1–53.4) and anti-beta2 glycoprotein I (OR = 3.5; 95%CI: 1.1–10.8), as well as cardiac disorders (OR = 8.0; 95%CI: 1.6–39.5). On the other hand, low concentrations of VEGF were significantly related to lower frequencies of anti-double-stranded DNA antibodies (OR = 0.31; 95%CI: 0.11–0.91) and anti-endothelial cell antibodies (OR = 0.30; 95%CI: 0.11–0.85). Patients with low VEGF levels showed significantly reduced risks of atherosclerotic lesions (OR = 0.24; 95%CI: 0.04–0.99) and vasculitis development (OR = 0.17; 95%CI = 0.03–0.91). Conclusions: In conclusion, VEGF’s pathogenetic role in SLE and SLE-related atherothrombosis is manifested in close correlation with aPLs which may enhance their direct impact on endothelium. High VEGF levels are helpful for identifying cardiovascular risk in patients, while low concentrations indicate lower disease activity, as well as a lower risk of organ involvement. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
21 pages, 5181 KiB  
Systematic Review
Beneficial Effect of Platelet-Rich Fibrin as an Adjunct to Nonsurgical Therapy After Subgingival Professional Mechanical Plaque Removal for Periodontitis: A Systematic Review and Meta-Analysis
by Monica Tanady, Fatimah Maria Tadjoedin, Sri Lelyati C. Masulili, Nadhia Anindhita Harsas and Adityo Widaryono
Clin. Pract. 2025, 15(7), 127; https://doi.org/10.3390/clinpract15070127 - 2 Jul 2025
Viewed by 450
Abstract
Background and Objectives: Periodontitis is an inflammatory disease that compromises the supporting structures of the teeth, leading to irreversible tissue damage and tooth loss. While subgingival professional mechanical plaque removal (PMPR) remains the gold standard treatment, there is increasing interest in adjunctive therapies. [...] Read more.
Background and Objectives: Periodontitis is an inflammatory disease that compromises the supporting structures of the teeth, leading to irreversible tissue damage and tooth loss. While subgingival professional mechanical plaque removal (PMPR) remains the gold standard treatment, there is increasing interest in adjunctive therapies. Platelet-rich fibrin (PRF) has gained attention as a promising biomaterial to enhance periodontal healing and regeneration. This study aimed to evaluate the clinical and immunological effectiveness of PRF as an adjunct to PMPR. Materials and Methods: Clinical studies published between January 2019 and August 2024 were included from the ProQuest, PubMed, PMC, ScienceDirect, Scopus, and EBSCO databases. Seven studies met the inclusion criteria, focusing on adults with periodontitis treated with PRF + PMPR compared to PMPR alone. Primary outcomes included changes in clinical and immunological parameters. Risk of bias was assessed using the Cochrane ROB2 tool. Meta-analysis was conducted using both fixed-effect and random-effects models, depending on heterogeneity. Results: The meta-analysis demonstrated significant improvements in clinical outcomes in the PRF + PMPR group, with reductions in probing pocket depth (SMD: −1.43 mm; 95% CI: −2.05 to −0.81; p < 0.00001), clinical attachment level (SMD: −1.34 mm; 95% CI: −1.95 to −0.73; p < 0.0001), bleeding on probing (SMD: −0.75 mm; 95% CI: −1.11 to −0.39; p < 0.00001), gingival recession (SMD: −0.79 mm; 95% CI: −1.33 to −0.25; p = 0.004), and gingival index (SMD: −0.82 mm; 95% CI: −1.37 to −0.28; p = 0.003). Favorable trends were also observed in IL-10, TGF-β, VEGF, PDGF-BB, periostin, and type I collagen levels. Conclusions: PRF enhances clinical and immunological outcomes and supports periodontal tissue stability when used as an adjunct to non-surgical therapy. Full article
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16 pages, 946 KiB  
Article
Impact of Heat Stress on Intake, Performance, Digestibility, and Health of Neonatal Dairy Calves
by Luiz F. M. Neves, Mariana B. Gomes, Joana P. Campolina, Mariana M. Campos, Eduardo M. B. Souza, Jaciara Diavão, Abias S. Silva, Thierry R. Tomich, Wanessa A. Carvalho, Helena F. Lage and Sandra G. Coelho
Animals 2025, 15(13), 1876; https://doi.org/10.3390/ani15131876 - 25 Jun 2025
Viewed by 439
Abstract
This study investigates the effects of heat stress in a climate chamber from day 0 to 28 days of life on physiological responses, intake, nutrient digestibility, immunity, and performance in neonatal Holstein calves. Thirty-four calves (nineteen females, fifteen males) were randomly assigned to [...] Read more.
This study investigates the effects of heat stress in a climate chamber from day 0 to 28 days of life on physiological responses, intake, nutrient digestibility, immunity, and performance in neonatal Holstein calves. Thirty-four calves (nineteen females, fifteen males) were randomly assigned to a control group (CON, temperature–humidity index [THI] 66, with 22 °C and 65% humidity for 24 h, n = 17) or a heat-stressed (HS) group, which was exposed to a THI of 82, 32 °C, and 65% humidity for 9 h, followed by a THI of 66, 22 °C, and 65% humidity for 15 h. The HS calves exhibited increased respiratory rates and rectal temperatures (p < 0.001), particularly during heat exposure periods, as well as a 59.5% increase in water intake compared to CON. While milk and solid feed intake, average daily gain, and feed efficiency were similar between groups, HS calves had reduced ether extract digestibility and altered ruminal fermentation, including lower acetate and lower propionate concentrations. The blood cytokine analysis showed elevated interleukin-4 and reduced interleukin-8 and IP-10 levels in heat-stressed calves, indicating a shift toward an anti-inflammatory immune profile. Despite no major performance impairments, heat stress has induced clear physiological, digestive, and immunological changes. These results underscore the importance of implementing thermal mitigation strategies during early life to safeguard calf health and development in increasingly warmer climates. Full article
(This article belongs to the Section Cattle)
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8 pages, 475 KiB  
Case Report
Ceftriaxone-Induced Pancytopenia: A Case Report
by Edin Karisik, Zorica Stanojevic-Ristic, Marija Jevtic, Julijana Rasic, Miljana Maric and Milica Popovic
Hematol. Rep. 2025, 17(3), 30; https://doi.org/10.3390/hematolrep17030030 - 12 Jun 2025
Cited by 2 | Viewed by 566
Abstract
Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of [...] Read more.
Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article
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40 pages, 10322 KiB  
Review
Applications of Osteoimmunomodulation Models in Evaluating Osteogenic Biomaterials
by Yuhan Wang, Yuzhu He, Yaran Zang, Zijiao Zhang, Guangyao Li, Wenqi Fu and Guowu Ma
J. Funct. Biomater. 2025, 16(6), 217; https://doi.org/10.3390/jfb16060217 - 11 Jun 2025
Viewed by 1133
Abstract
The development of osteogenic biomaterials relies on updates in research methodologies. Establishing reasonable modes is the basis for obtaining reliable experimental conclusions. With the advancement in bone immunology, osteoimmunomodulatory properties have become one of the crucial indexes for evaluating osteogenic biomaterials. Summarizing the [...] Read more.
The development of osteogenic biomaterials relies on updates in research methodologies. Establishing reasonable modes is the basis for obtaining reliable experimental conclusions. With the advancement in bone immunology, osteoimmunomodulatory properties have become one of the crucial indexes for evaluating osteogenic biomaterials. Summarizing the current models of bone immunomodulation is beneficial for optimizing experimental protocols and promoting the clinical application of osteogenic biomaterials. In this review, we introduced the crosstalk between the skeletal system and the immune system, in particular, the roles of different immune cells in the process of bone regeneration. Moreover, the mechanisms of osteogenic biomaterials in regulating the osteoimmune microenvironment were analyzed, followed by summarizing the benefits and limitations of current osteoimmunomodulation models in evaluating osteogenic biomaterials. Finally, we discussed the expected future directions of the applications of osteoimmunomodulation models. Full article
(This article belongs to the Section Bone Biomaterials)
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18 pages, 2527 KiB  
Article
Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection
by Masood A. Khan, Arif Khan, Abdullah M. Alnuqaydan, Aqel Albutti, Basmah F. Alharbi and Mohammad Owais
Vaccines 2025, 13(6), 630; https://doi.org/10.3390/vaccines13060630 - 11 Jun 2025
Viewed by 988
Abstract
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential [...] Read more.
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article
(This article belongs to the Special Issue Peptide-Based Vaccines)
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12 pages, 345 KiB  
Article
Acute Respiratory Tract Infection and Sudden Sensorineural Hearing Loss: A Multinational Cohort Study
by Chien-Hsiang Weng, Jun-Fu Lin and Jing-Jie Wang
Diagnostics 2025, 15(12), 1462; https://doi.org/10.3390/diagnostics15121462 - 9 Jun 2025
Viewed by 560
Abstract
Background/Objectives: Sudden sensorineural hearing loss (SSNHL) is an acute condition with unclear etiology, commonly hypothesized to be associated with viral infections. Acute respiratory tract infections (RTIs), particularly those of viral origin, have been implicated in SSNHL through proposed mechanisms such as cochlear invasion [...] Read more.
Background/Objectives: Sudden sensorineural hearing loss (SSNHL) is an acute condition with unclear etiology, commonly hypothesized to be associated with viral infections. Acute respiratory tract infections (RTIs), particularly those of viral origin, have been implicated in SSNHL through proposed mechanisms such as cochlear invasion and immune-mediated damage. However, robust large-scale epidemiological evidence examining this association remains limited. This study aimed to investigate the potential association between acute RTIs and subsequent risk of developing SSNHL across diverse populations. Methods: We conducted a multinational retrospective cohort study using data from the TriNetX Global Collaborative Network. Adults diagnosed with acute RTIs between 1 January 2012 and 30 June 2023 were compared to matched controls without RTI exposure. Patients with predisposing conditions for SSNHL were excluded. Propensity score matching (1:1) was performed by age and sex. SSNHL diagnoses within 60 days post index were analyzed using Cox proportional hazards models. Subgroup and sensitivity analyses were conducted by race, sex, and age strata. Results: Among 37 million patients analyzed, individuals with acute RTIs had a lower incidence of SSNHL compared to matched controls. Hazard ratios (HRs) for SSNHL were significantly reduced across all racial groups: Whites (HR: 0.572), Blacks (HR: 0.563), and Asians (HR: 0.409). Subgroup analyses revealed stronger inverse associations in males and younger age groups, particularly those aged 18–25 years. Conclusions: Contrary to prior assumptions, acute RTIs were associated with a lower incidence of SSNHL in a large, diverse cohort. While the findings raise the possibility of immunological or physiological factors influencing this association, the results should be interpreted with caution due to unmeasured confounding and the observational nature of the study. Full article
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11 pages, 482 KiB  
Article
Immunological Markers of Cardiovascular Pathology in Older Patients
by Akbota Bugibayeva, Almagul Kurmanova, Kuat Abzaliyev, Symbat Abzaliyeva, Gaukhar Kurmanova, Diana Sundetova, Merei Abdykassymova, Raushan Bitemirova, Ulzas Sagalbayeva, Karashash Absatarova and Madina Suleimenova
Biomedicines 2025, 13(6), 1392; https://doi.org/10.3390/biomedicines13061392 - 6 Jun 2025
Viewed by 591
Abstract
Background: The aging process is accompanied by changes in the immunological status of a person. Immunosenescence is considered a significant cause of the development of cardiovascular diseases (CVD) in elderly people. However, to date, the relationship between immune/inflammatory processes and diseases associated with [...] Read more.
Background: The aging process is accompanied by changes in the immunological status of a person. Immunosenescence is considered a significant cause of the development of cardiovascular diseases (CVD) in elderly people. However, to date, the relationship between immune/inflammatory processes and diseases associated with age is considered quite complex and is not fully understood. Immunophenotyping and the intracellular production of cytokines involved in the processes of inflammatory aging will allow us to identify biomarkers that are associated with cardiovascular diseases in the elderly. Objectives: To identify immunological markers associated with the process of inflammatory aging in older individuals with cardiovascular diseases. Methods: CD-phenotyping and intracellular cytokine analysis of peripheral blood using the flow cytometry method were conducted in 52 people over 60 years of age (group 1 had CVD and group 2 did not). Blood samples were stained with monoclonal antibodies (mAb) using Becton Dickinson (BD) reagents for the staining and binding of surface receptors CD4+, CD8+, CD14+, CD19+, CD16+, CD56+, CD59+, CD95+, and HLA DR+ and intracellular receptors TNF, IL-10, GM-CSF, VEGFR-2, IGF, and perforin. In addition, the following parameters were studied: questionnaire data (gender, age, alcohol consumption, smoking, physical activity, and marital status), clinical data (blood pressure (BP), heart rate (HR), body mass index (BMI)), comorbid conditions, and cardiovascular diseases (coronary heart disease (CHD), chronic heart failure (CHF), arterial hypertension (AH), previous myocardial infarction (PICS), diabetes mellitus (DM), atrial fibrillation (AF), and stroke). Results: The older patients with cardiovascular pathology had high levels of monocytes CD14+ (p = 0.014), low levels of CD8+ lymphocytes (p = 0.046), and low intracellular production of GM-CSF (p = 0.013) compared to the older people without CVD. Conclusions: The revealed differences in the expression of CD14+ monocytes indicate their role in the development of cardiovascular pathology associated with age-related changes. A decrease in cytotoxic CD8+ lymphocytes and intracellular GM-CSF production leads to an increased risk of developing cardiovascular diseases in older individuals. These observed changes with age will not only expand existing knowledge about the aging of the regulatory link of the immune system but also help to obtain data to predict CVD in older people. Thus, the obtained results support the use of these immunological markers to identify the risk of circulatory disease and a personalized approach in geriatric practice. Full article
(This article belongs to the Special Issue Inflammaging and Immunosenescence: Mechanisms and Link)
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19 pages, 3614 KiB  
Article
Immunoenhancement Function of the Novel Hexapeptide (LVVLGH) from Thick-Shelled Mussel (Mytilus coruscus) on Immunodeficient Mice by Activating the NF-κB/MAPK Pathway
by Xu Yang, Yu Zeng, Fandi Que, Shiqing Fu, Li Xu, Fangmiao Yu and Bin Wang
Foods 2025, 14(11), 1865; https://doi.org/10.3390/foods14111865 - 24 May 2025
Viewed by 555
Abstract
A novel hexapeptide LVVLGH (LH-6) from the thick-shelled mussel (Mytilus coruscus) demonstrated potent immune-enhancing effects in RAW264.7 cells in vitro, but its immunological activity in vivo is unclear. As a result, the present study was designed to investigate the in vivo [...] Read more.
A novel hexapeptide LVVLGH (LH-6) from the thick-shelled mussel (Mytilus coruscus) demonstrated potent immune-enhancing effects in RAW264.7 cells in vitro, but its immunological activity in vivo is unclear. As a result, the present study was designed to investigate the in vivo effects of LH-6 on cyclophosphamide-induced immunodeficient mice. The results demonstrate that LH-6 promoted the growth and development of immunodeficient mice in a concentration-dependent manner, remarkably elevated the immune organ index, and relieved the pathological characteristics of the spleen and thymus. Additional experiments also revealed that LH-6 effectively promoted the multiplication of splenic lymphocytes and natural killer activity, enhanced the function of abdominal macrophages, and apparently recovered delayed-type hypersensitivity in immunodeficient mice. The secretion of IgA, IgG, IgM, TNF-α, IL-1β, IL-6, and serum hemolysin were remarkably improved by LH-6, suggesting that LH-6 can synergistically strengthen cellular and humoral immunity. In addition, LH-6 promoted the phosphorylation of IκBα and nuclear translocation of p65, which correspondingly increased the phosphorylation levels of p38, JNK, and ERK; activated the NF-κB and MAPK pathways; and exerted in vivo immunomodulatory activities. Docking results show that LH-6 has favorable binding energies to candidate proteins in the NF-κB and MAPK pathways. To summarize, this research further demonstrated that LH-6 possesses in vivo immunomodulatory activity, which provides a possibility for the subsequent development of immune-enhancing functional foods. Full article
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12 pages, 638 KiB  
Article
Adherence to Mediterranean Diet and Ocular Dryness Severity in Sjögren’s Syndrome: A Cross-Sectional Study
by Celine Chaaya, Elie Raad, Francesca Kahale, Elias Chelala, Nelly Ziade and Georges Maalouly
Med. Sci. 2025, 13(2), 64; https://doi.org/10.3390/medsci13020064 - 23 May 2025
Cited by 1 | Viewed by 615
Abstract
Background: Sjögren’s syndrome (SS) is a multifaceted clinical condition characterized by various features, including ocular dryness (OD), which plays a substantial role in shaping the clinical presentation of the disease and has detrimental effects on quality of life. Recent research has acknowledged [...] Read more.
Background: Sjögren’s syndrome (SS) is a multifaceted clinical condition characterized by various features, including ocular dryness (OD), which plays a substantial role in shaping the clinical presentation of the disease and has detrimental effects on quality of life. Recent research has acknowledged the advantages of the Mediterranean diet (MD) for its positive impact on various autoimmune diseases. This study aims to investigate the correlation between the severity of ocular symptoms in individuals with SS and adherence to the MD. Methods: This was a cross-sectional observational study of previously diagnosed SS patients recruited from the histopathological and immunological archives of a university hospital. The data were collected through a telephone questionnaire, including demographic and disease data, the Ocular Surface Disease Index (OSDI) score to evaluate the OD severity, and the Mediterranean Diet Adherence Screener (MEDAS) score to determine adherence to the MD. The primary outcome of the study, the correlation between OSDI and MEDAS scores, was evaluated using Spearman’s correlation coefficient. Results: The study included 114 patients, with a mean age of 51 (±13.4) years and a female proportion of 86%. OD was documented in 80.7% of the patients. The median OSDI and MEDAS scores were 23 (IQR 10–40) and 8 (IQR 5–11), respectively. A strong negative correlation was observed between the MEDAS and the OSDI scores (ρ = −0.73, p < 0.01). Additionally, there was a significant negative relationship between the richness of diet in fatty acids and the OSDI score (ρ = −0.67, p < 0.01). Conclusions: The study results suggest an association between lower OD severity in patients with SS and adherence to the MD, particularly the components related to polyunsaturated fatty acids consumption. This approach may serve as a complementary strategy with multiple health benefits, alongside conventional treatment options. Full article
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10 pages, 792 KiB  
Article
Role of ACE1, ACE2, and CCR5-Δ32 Polymorphisms in the Transmission of SARS-CoV-2 to Intimate Contacts
by Maria Pina Dore, Alessandra Errigo, Elettra Merola and Giovanni Mario Pes
Biology 2025, 14(6), 587; https://doi.org/10.3390/biology14060587 - 22 May 2025
Viewed by 418
Abstract
Background. Despite the high transmissibility of SARS-CoV-2, some individuals remain uninfected despite prolonged exposure to a high viral load, suggesting the involvement of an innate resistance mechanism, possibly underpinned by the host’s genetic factors. The angiotensin-converting enzyme-1 (ACE1), ACE2, and [...] Read more.
Background. Despite the high transmissibility of SARS-CoV-2, some individuals remain uninfected despite prolonged exposure to a high viral load, suggesting the involvement of an innate resistance mechanism, possibly underpinned by the host’s genetic factors. The angiotensin-converting enzyme-1 (ACE1), ACE2, and C-C Chemokine Receptor 5 (CCR5) polymorphisms have been shown to influence susceptibility to the infection. In this study, the role of ACE1, ACE2, and CCR5 gene polymorphisms in modulating susceptibility to SARS-CoV-2 infection within the context of intimate contact was evaluated. Methods. A cohort of heterosexual couples from Northern Sardinia, characterized by a homogenous genetic background, was recruited during the initial pandemic wave (March–June 2020). In each couple, one partner (index case) tested positive for SARS-CoV-2 by at least two consecutive independent molecular tests (real-time polymerase chain reaction: RT-PCR) on nasopharyngeal swabs. Bed-sharing partners of SARS-CoV-2 positive index cases, resistant and susceptible to the infection, were genotyped for ACE1 287 bp Alu repeat insertion/deletion (I/D) polymorphism, ACE2 G8790A (rs2285666) variant, and a 32-base pair deletion (Δ32) of CCR5. Resistant and susceptible partners to the infection were compared for polymorphisms. Results. Out of 63 couples, 30 partners acquired SARS-CoV-2 infection, while 33 remained uninfected despite intimate exposure. Clinical history was minimal for current or past illnesses. SARS-CoV-2-infected index spouses and partners who acquired the infection developed a mild disease, not requiring hospitalization. The observed distribution of ACE1 I/D and ACE2 G8790A genotypes was consistent with previously reported frequencies in Sardinia and across European populations. None of the study participants carried the CCR5-Δ32 variant. No statistically significant differences (p > 0.05) in the allelic or genotypic frequencies of these polymorphisms were observed between the infected and resistant partners. Conclusions. No differences in the distribution of ACE1, ACE2, and CCR5 polymorphisms between the two groups were detected. These findings suggest that resistance is likely multifactorial, involving a complex interplay of genetic, immunological, and environmental factors. Full article
(This article belongs to the Section Infection Biology)
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21 pages, 3742 KiB  
Article
Clinical Periodontal Evaluation and Assessment of Dipeptidyl-Peptidase-4 and Galectin-3 in Gingival Crevicular Fluid of Periodontitis Patients with Heart Failure and Diabetes
by Ana Păvălan, Mihail Virgil Boldeanu, Flavia Mirela Nicolae, Theodora Claudia Gheonea, Ion Rogoveanu, Cristina Florescu, Adina Turcu-Știolică, Dorin Nicolae Gheorghe, Dora Maria Popescu, Andrada Șoancă, Alexandra Roman and Petra Șurlin
J. Clin. Med. 2025, 14(10), 3345; https://doi.org/10.3390/jcm14103345 - 12 May 2025
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Abstract
Background/Objectives: Periodontitis, a prevalent chronic inflammatory disease affecting tooth-supporting structures, has been increasingly linked to systemic conditions such as diabetes mellitus (DM) and cardiovascular diseases (CVDs). This study aimed to evaluate the periodontal status and levels of dipeptidyl peptidase-4 (DPP-4) and galectin-3 [...] Read more.
Background/Objectives: Periodontitis, a prevalent chronic inflammatory disease affecting tooth-supporting structures, has been increasingly linked to systemic conditions such as diabetes mellitus (DM) and cardiovascular diseases (CVDs). This study aimed to evaluate the periodontal status and levels of dipeptidyl peptidase-4 (DPP-4) and galectin-3 (Gal-3) in gingival crevicular fluid (GCF) of patients with periodontitis, heart failure (HF), and diabetes, exploring their potential as biomarkers for disease association. Methods: A cross-sectional study was conducted on 88 patients categorized into four groups: periodontally and systemically healthy (control, C); periodontitis (P); periodontitis and HF (P+HF); and periodontitis, HF, and diabetes (P+HF+D). Periodontal status was assessed using probing pocket depth (PPD) and Gingival Index (GI). GCF samples were collected and analyzed for DPP-4 and Gal-3 levels using ELISA. Statistical analyses were performed to assess differences between groups and potential correlations. Results: Results indicated significantly higher levels of DPP-4 in all test groups compared to controls (p < 0.0001), with the highest levels in the P+HF+D group. Similarly, Gal-3 levels were elevated in periodontitis patients, particularly in those with HF (p < 0.0001), and there was no significant difference between P+HF and P+HF+D groups. No significant differences were observed between smokers and non-smokers regarding these markers. Positive correlations were found between the periodontal parameters and the immunological markers in all test groups. Conclusions: The findings suggest that DPP-4 and Gal-3 may serve as potential biomarkers for periodontitis in association with heart failure and diabetes, with DPP-4 being more upregulated in the association with diabetes and Gal-3 with heart failure. Full article
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15 pages, 1909 KiB  
Article
Early Immunological and Inflammation Proteomic Changes in Elderly COVID-19 Patients Predict Severe Disease Progression
by Shiyang Liu, Wen Xu, Bo Tu, Zhiqing Xiao, Xue Li, Lei Huang, Xin Yuan, Juanjuan Zhou, Xinxin Yang, Junlian Yang, De Chang, Weiwei Chen and Fu-Sheng Wang
Biomedicines 2025, 13(5), 1162; https://doi.org/10.3390/biomedicines13051162 - 10 May 2025
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Abstract
Background: Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. Methods: We enrolled 182 elderly COVID-19 patients from the Chinese PLA [...] Read more.
Background: Elderly patients infected with SARS-CoV-2 are at higher risk of developing cytokine storm and severe outcomes; however, specific immunological and proteomic biomarkers for early prediction remain unclear in this vulnerable group. Methods: We enrolled 182 elderly COVID-19 patients from the Chinese PLA General Hospital between November 2022 and April 2023, categorizing them based on progression to respiratory failure requiring mechanical ventilation (defined as severe progression). Olink proteomic analysis was performed on admission serum from 40 propensity score-matched samples, with differentially expressed proteins (DEPs) validated by cytometric bead array (CBA) in 178 patients. To predict severe progression, a model was developed using a 70% training set and validated on a 30% validation set. LASSO regression screened features followed by logistic regression and receiver operating characteristic (ROC) analysis to optimize the model by incrementally incorporating features ranked by random forest importance. Results: Elderly patients progressing to severe COVID-19 exhibited early immune dysregulation, including neutrophilia, lymphopenia, monocytopenia, elevated procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as coagulation dysfunction and multi-organ injury. Proteomics identified a set of biomarkers, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and revealed disruptions in signaling pathways, including the mTOR and VEGF signaling pathways. The optimal predictive model, which incorporated PCT, IL-6, monocyte percentage, lymphocyte count, and TRAIL, achieved an area under curve (AUC) of 0.870 (0.729–1.000) during validation. TRAIL levels negatively correlated with fibrinogen (p < 0.05). Conclusions: Elderly COVID-19 patients with severe progression demonstrate early immune dysregulation, hyperinflammation, coagulation dysfunction, and multi-organ injury. The model we proposed effectively predicts disease progression in elderly COVID-19 patients, providing potential biomarkers for early clinical risk stratification in this vulnerable population. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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