Search Results (6,026)

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in infants, the elderly, and immunocompromised persons. Innate immune responses to RSV, which are crucial for containment of the infection yet may also be linked to severe disease, are well-studied in the main RSV target cells, respiratory epithelial cells, but the role of pulmonary macrophages (MΦs), key innate immune regulators, remains incompletely defined. This review addresses the interaction of RSV with MΦ, discussing the susceptibility of these cells to productive infection, and MΦ responses to RSV, including cytokine and chemokine release and inflammasome activation. Furthermore, factors contributing to variability in MΦ infectivity and responses, such as MΦ polarization, age, differences in RSV isolates, co-infections, and prior innate priming, are presented. Finally, the review highlights discrepancies observed across experimental models, MΦ origins, and RSV isolates used, complicating the interpretation of MΦ-RSV interactions, thereby underscoring the need for standardized methodologies. Full article

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidative phosphorylation; the secretion of adipokines such as leptin and IL-6, which promote epithelial-to-mesenchymal transition, invasion, and immune evasion; regulation of osteoclastogenesis via RANKL expression; and the release of extracellular vesicles that reprogram cancer cell metabolism. Clinical and experimental studies show that BMA expansion correlates with increased tumor burden and poorer outcomes in breast, prostate, lung cancers, and multiple myeloma. Additionally, BMAs actively promote therapeutic resistance through metabolic rewiring and drug sequestration. Experimental models, ranging from in vitro co-cultures to in vivo patient-derived xenografts, demonstrate the complex roles of BMAs and also reveal important translational gaps. Despite promising preclinical approaches such as metabolic inhibitors, PPARγ modulation, adipokine blockade, and lifestyle changes, no therapies directly targeting BMAs have yet reached clinical practice. This review compiles current evidence on the biology of BMAs, their tumor-promoting interactions, and potential therapeutic strategies, while also highlighting unresolved questions about BMA heterogeneity, lipid flux, and immunometabolic crosstalk. By revealing how bone marrow adipocytes actively shape the metastatic niche through metabolic, endocrine, and immunological pathways, this review highlights their potential as novel biomarkers and therapeutic targets for improving the management of bone metastases. Full article

Background/Objectives: This review article highlights the role of the nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing 3 protein (NLRP3) inflammasomes in various gastrointestinal and hepatic disorders in the pediatric age group. NLRP3 inflammasomes are one of the principal intracellular innate immune sensors. During inflammation, molecules such as caspase-1 and the release of IL-1β and IL-18 are produced. The NLRP3 inflammasome participates in the preservation of intestinal homeostasis and mucosal immune response. The objective is to evaluate the published articles related to the role of NLRP3 inflammasomes in common pediatric gastrointestinal and hepatic disorders in order to identify the future perspective regarding their possible therapeutic values. Methods: We searched Medline for NLRP3 inflammasomes and disorders of the digestive system during childhood. Results: Although the majority of articles were related to various disorders of adults, such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, as well as neurodevelopmental disorders, such as schizophrenia, a few published datasets were related to the roles of NLRP3 in the pediatric age group: they addressed autism, rheumatoid arthritis, and other autoimmune diseases, as well as inflammatory bowel diseases (IBD) and hepatic infection. Some research demonstrated that the NLRP3 inflammasome has a protective role; however, it also has a pathogenic function. Conclusions: This review focused on the comprehensive role of inflammasome NLRP3 in the most common pediatric and neonatal gastrointestinal and hepatic diseases, including clinical and experimental studies, as well as the pharmacological inhibitors for NLRP3 inflammasomes, which may provide future therapy for GIT problems, such as IBD. Full article

Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical–biochemical diagnostic panel to identify the possible cause(s) of non-response in each non-responder and changing the treatment plan in each particular patient accordingly. Patients and methods: Our study included 64 eyes of 40 patients with DME (Group A, DME patients) and 40 eyes of 40 healthy individuals matched for age and sex (Group B, controls). Blood and aqueous samples were collected from the study participants before and one month after IVR injection. The DME patients were further subdivided into responders and non-responders according to their response to the first IVR injection. Lymphocyte activation markers, NETosis markers, angiogenic factors, astrocytes, innate immunity, and inflammasome markers were assessed in both groups. Results: Multivariate regression analysis revealed that macular ischemia, aqueous levels of hexokinase 1, SELL CD62L, ELANE, MPO, VEGFA, and SEMA4D were the most significant factors affecting the response to IVR (p < 0.05). Conclusions: defining our DME patients as responders and non-responders after the first IVR injection, combined with potential utilization of a clinical–biochemical panel (macular ischemia- PCR array of combined Hexokinase 1, MPO, and SEMA4D) in each non-responder, may represent a good starting point for changing the current DME management strategy. Full article

Background/Objectives: Human colostrum plays a crucial role in early microbial colonization, immune development, and gut health of newborns. Its microbiota is highly dynamic and influenced by numerous factors, yet the determinants remain poorly understood. This systematic review aims to investigate the composition of colostrum microbiota and the intrinsic and extrinsic factors that influence its diversity and abundance. Methods: PubMed and Scopus were systematically searched using a prespecified search phrase. Data on microbial composition, diversity, and influencing factors were extracted and analyzed. The systematic review is registered in PROSPERO (CRD42025644017). Results: A total of 44 eligible studies involving 1982 colostrum samples were identified. Colostrum microbiota consists predominantly of Firmicutes and Proteobacteria, with core genera including Staphylococcus, Streptococcus, Lactobacillus, and Bifidobacterium. Some studies reported higher diversity in colostrum compared to mature milk, while others noted elevated bacterial abundance in the former. Factors influencing colostrum microbiota include maternal BMI, delivery mode, gestational age, diet, gestational diabetes mellitus (GDM), maternal stress, maternal age, secretor status, perinatal antibiotic exposure, neonatal gender, geographic location, feeding type, milk collection method, and mastitis. Conclusions: Colostrum hosts a diverse and dynamic microbiota shaped by multiple maternal, neonatal, and environmental factors. Understanding these influences is crucial for optimizing infant health outcomes, emphasizing the need for further research on the functional roles of colostrum’s microbiota. Full article

Nowadays, two major pathways seem to be responsible for the development and progression of atherosclerosis, namely, high levels of low-density lipoprotein-cholesterol (LDL-C) and low-grade vascular inflammation. Indeed, the concentration of C-reactive protein (CRP), mirroring low-grade systemic inflammation, has been recognized as a more powerful determinant of recurrent cardiovascular (CV) events, death, and all-cause mortality than LDL-C levels. Gut microbiota (GM) dysbiosis is a causal factor for the development of different inflammatory-based pathologies, such as CV disease (CVD). In addition, pre/probiotics showed beneficial effects on GM dysbiosis, by influencing both inflammation and immunity. It has been well documented that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert triglyceride (TG)-lowering and antithrombotic effects and play a seminal role in the resolution of inflammatory processes. We showed the recent studies indicating the relationship between pharmacological reduction in inflammatory cytokines and CV outcomes. The principal aim of our review is to highlight the anti-inflammatory and immune-modulatory activities of GM, EPA, and DHA. Then, we pointed out how developing patient-specific pre/probiotic and EPA/DHA interventions alongside the standard of care (SOC) is needed in order to answer several of the questions raised, ranging from diminishing drug toxicity to including frailty individuals. Therefore, hypothetical tailored clinical studies are presented, aiming to treat all the patients at high-risk of CV events, as well as aged people. Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also exist in soluble forms, reflecting systemic immune balance. Objective: To compare immune checkpoint profiles in IgAN and MPGN versus healthy volunteers (HV) through surface expression, soluble serum levels, and PBMC transcripts, with attention to sex-related differences and diagnostic value assessed by ROC curves. Materials and Methods: Ninety age-matched subjects were studied: IgAN (n = 30), MPGN (n = 30), HV (n = 30). Flow cytometry evaluated checkpoint expression on CD4+/CD8+ T cells, CD19+ B cells, and NK cells. ELISA quantified sPD-1, sPD-L1, sCTLA-4, sCD86, sCD200, sCD200R; PBMC transcript levels were assessed. Group comparisons, sex stratification, and ROC analyses were performed. Results: Lymphocyte distributions were preserved, but IgAN patients showed anemia and impaired renal function, while MPGN patients had greater proteinuria and dyslipidemia. GN patients displayed increased PD-1/PD-L1 and CD200R/CD200, with reduced CTLA-4/CD86, compared to HV. Serum analysis revealed elevated sPD-1, sPD-L1, sCD200, sCD200R and decreased sCTLA-4, sCD86. PBMC transcripts paralleled these trends, with PD-1/PD-L1 mainly increased in MPGN. Sex had minimal impact. ROC analyses showed strong GN vs. HV discrimination by CD19⁺CTLA-4⁺, PD-1/PD-L1, and CD200/CD200R, but limited ability to separate IgAN from MPGN. Conclusions: IgAN and MPGN share a sex-independent checkpoint signature: PD-1/PD-L1 and CD200R/CD200 upregulation with CTLA-4/CD86 downregulation. CD19⁺, CTLA-4⁺, and soluble PD-1/PD-L1/CD200(R) emerge as promising biomarkers requiring further validation. Full article

Healthcare-associated infections (HAIs) in the elderly represent a growing clinical and public health concern, primarily driven by age-related biological remodeling. Key mechanisms include immunosenescence, inflammaging, gut microbiota dysbiosis, and profound metabolic and epigenetic alterations, all of which progressively weaken host defense and resilience to pathogens. In this review, we delineate the molecular pathways underlying these processes, with particular attention to impaired innate and adaptive immune responses, dysfunctional cellular signaling, and disrupted immunometabolic networks that increase susceptibility to multidrug-resistant organisms and aggravate clinical outcomes in older patients. We also address the synergistic impact of frailty-related factors such as malnutrition, multimorbidity, and polypharmacy on infection risk. Finally, we discuss emerging translational perspectives, including nutritional interventions and microbiota-targeted strategies aimed at restoring immune competence and reducing infection burden. By integrating molecular mechanisms with clinical implications, this review highlights innovative opportunities for personalized prevention and management of HAIs in the aging population. Full article

Background: The 4CMenB vaccine (Bexsero^®) contains surface proteins from Neisseria meningitidis serogroup B and is recommended from 2 months of age. The most frequently reported adverse events are fever, injection site pain, and fatigue. Thus, this study aimed to estimate the incidence of local and systemic adverse events associated with the administration of the 4CMenB (Bexsero^®) vaccine. Methods: A systematic review and meta-analysis of clinical trials published up to 28 February 2025 were conducted using PubMed, ScienceDirect, and Web of Science. Human studies available in English, Spanish, French, German, or Italian were exclusively included. Adverse events following the first dose of the vaccine were analyzed. Pooled proportions with 95% confidence intervals were calculated, and heterogeneity across studies was assessed using the I² statistics. Results: Ten clinical trials comprising 13,345 participants were included. The most common adverse event was local pain (occurring in up to 94% of cases), followed by induration, erythema, and edema, with frequencies ranging from 25% to 45%. The most frequently reported systemic events were irritability (up to 75%), fatigue (51–59%), fever (up to 60%), headache (42–49%), and persistent crying (50–65%). Most adverse events were mild and self-limiting. Conclusions: The 4CMenB (Bexsero) vaccine exhibits a favorable safety profile, characterized by a predominance of mild and transient local adverse events. Although several systemic events were reported, their overall frequency was generally low. These findings support the continued inclusion of Bexsero^® in routine childhood immunization programs. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency following primary infection, residing within myeloid progenitor cells and monocytes. To achieve this, the virus employs multiple immune evasion strategies. It suppresses innate immune signaling by inhibiting Toll-like receptor and cGAS-STING pathways. In addition, the virus suppresses major histocompatibility complex (MHC)-dependent antigen presentation to evade T cell recognition. As the downregulation of MHC molecules may trigger NK cell activation, the virus compensates for this by expressing proteins such as UL40 and IL-10, which engage inhibitory NK cell receptors and block activating signals, thereby suppressing NK cell immune surveillance. Viral proteins like UL36 and UL37 block host cell apoptosis and necroptosis, allowing HCMV to persist undetected and avoid clearance. In settings of profound immunosuppression, such as after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation, slow immune reconstitution creates a window for viral reactivation. Likewise, immunosenescence and chronic low-grade inflammation during aging increases the risk of reactivation. Once reactivated, HCMV triggers programmed cell death, releasing viral PAMPs (pathogen-associated molecular patterns) and host-derived DAMPs (damage-associated molecular patterns). This release fuels a potent inflammatory response, promoting further viral reactivation and exacerbating tissue damage, creating a vicious cycle. This cycle of inflammation and reactivation contributes to both transplant-related complications and the decline of antiviral immunity in the elderly. Therefore, understanding the immune regulatory mechanisms that govern the switch from latency to reactivation is critical, especially within the unique immune landscapes of transplantation and aging. Elucidating these pathways is essential for developing strategies to prevent and treat HCMV-related disease in these high-risk populations. Full article

Emerging evidence highlights oxidative stress and its biomarkers as potential factors in the onset and maintenance of Post-Traumatic Stress Disorder (PTSD) and co-occurring sleep disturbances. The study concerns the profile of biomarkers including glutamine, glutathione (GSH), caspase-1 and Brain-Derived Neurotrophic Factor (BDNF) levels in three groups (PTSD with a current diagnosis lasting ≤ 5 years, PTSD with a current diagnosis lasting > 5 years, and no PTSD), classified into two age groups. In addition, sleep disturbances were analyzed using the Pittsburgh Sleep Quality Index Addendum (PSQI-A). The study revealed mutual correlations between the examined biomarkers, which may confirm a coordinated antioxidant response. Furthermore, a relationship was observed between biomarkers and PSQI-A; trauma-related domains (e.g., Trauma Nightmares with Terror Episodes) were more pronounced in the case of PTSD ≤ 5 years, while PTSD > 5 years emphasized trauma-unrelated anxiety. The study results suggest that individuals with PTSD exhibit increased sensitivity to trauma, which may manifest through immune system activation and sleep disturbances. Patients with a longer history of PTSD and co-occurring dysfunctions require a personalized approach to trauma treatment and prevention of recurrence. Full article

Introduction: The analysis of exhaustion marker expression, like immune checkpoint molecules (ICMs) on tumor-infiltrating lymphocytes as well as peripheral immune cells of patients with head and neck squamous cell carcinoma (HNSCC), is of high interest since it reveals information about the patient’s immune status and the effectiveness of immune modulation. However, data regarding age-dependent expression are lacking. Here, we demonstrate an increase in most ICMs associated with age and disease, suggesting immune checkpoint modulation as an evidence-based option for the treatment of aged HNSCC patients. Material and Methods: Peripheral blood mononuclear cells (PBMCs) (healthy: n = 30 with an age range from 21 to 84 years/HNSCC: n = 37 with an age range from 37 to 94 years) were analyzed via flow cytometry following (density gradient separation) standard protocol. Flow cytometry was performed using CD4 and CD8 as backbone markers as well as co-stimulatory molecules like CD137, OX40, GITR, and CD27 or ICM like PD-1, CTLA4, BTLA, LAG3, or TIM3 using a Gallios flow cytometer (Beckman Coulter, Brea, CA, USA). Results: We found a statistically significant decreased ICM expression on the PBMCs of healthy donors with increasing age. However, the expression of ICMs in HNSCC was significantly increased (PD1 on CD4⁺ T cells: p = 0.001), while we found a decreased co-stimulatory molecule expression (e.g., CD27 on CD4⁺ T cells and CD39⁺ T cells: p = 0.003 and p = 0.009, respectively). Immune cells of HPV^neg HNSCC have a significant age-dependent decrease in CD27 expression on CD8⁺, CD4⁺, and CD39⁺ T cells (p = 0.0426, p = 0.0078, and p = 0.0078, respectively). Conclusions: This study sheds light on the changing co-stimulatory molecule/ICM expression regarding the patient’s age and reveals an increase in most immune checkpoint molecules for HNSCC patients according to their age. This new evidence is valuable in ensuring individualized therapeutic approaches in the increasingly relevant field of checkpoint inhibition, even in old age. Full article

Background. Melioidosis is a severe infection caused by Burkholderia pseudomallei and is endemic in regions with a high prevalence of thalassemia. Patients with thalassemia are thought to be at increased risk due to iron overload, splenectomy, and immune dysfunction. However, the pooled prevalence and mortality outcomes of melioidosis in this population remain unclear. Methods. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420251108294). PubMed, Embase, and Scopus were searched from inception to July 2025. Observational studies reporting prevalence or mortality of melioidosis in patients with thalassemia were eligible. Pooled odds ratios (ORs) for mortality were calculated using random-effects models, with subgroup and sensitivity analyses based on age, thalassemia subtype, and study quality. Results. Six retrospective studies including 7529 melioidosis patients, of whom 173 had thalassemia, were analyzed. The prevalence of thalassemia among melioidosis cases ranged from 0.5% to 40.7%. Mortality among thalassemia patients varied from 0% to 100%. Pooled analysis demonstrated no significant excess mortality compared with non-thalassemia controls (OR 0.55, 95% CI 0.16–1.89; I² = 44.9%). Sensitivity analysis restricted to moderate- and high-quality studies showed a significantly lower risk of death (OR 0.23, 95% CI 0.15–0.36; I² = 0%). Subgroup analyses by thalassemia subtype and age revealed no clear effect modification, although power was limited. Conclusions. Despite biological plausibility, thalassemia was not associated with increased melioidosis mortality. These findings suggest that closer clinical monitoring, iron chelation, and comorbidity profiles may influence outcomes. Prospective, well-characterized cohort studies are needed to refine risk stratification and guide management in endemic regions. Full article

The aim of this study was to evaluate the effects of Flos lonicerae and Baikal skullcap extracts (PE) on laying performance, antioxidant capacity, immune function, follicular development, estrogen secretion, ovarian metabolomics, and cecal microbiota in aged laying hens. The total number of 70-week-old XinYang Black-Feathered laying hens was 240. These hens were randomly divided into two groups, with each group consisting of six replicates of 20 birds. Control (CON) group was fed a basal diet, whereas the PE group received the same basal diet supplemented with 500 mg/kg of PE. The duration of the experiment was 10 weeks. The findings indicated that the supplementation of PE improved laying performance, antioxidant capacity, and immune function. This was reflected by significant increases (p < 0.05) in laying rate, feed conversion ratio, antioxidant indicators (such as glutathione peroxidase, total antioxidant capacity, and catalase), and immunoglobulin levels. Additionally, there were notable decreases (p < 0.05) in the malondialdehyde levels and pro-inflammatory markers. Moreover, the PE group exhibited a greater number of large yellow and white follicles, as well as higher serum estrogen levels, compared to the CON group (p < 0.05). 16S rRNA sequencing revealed that PE supplementation altered the composition of the cecal microbiota by increasing Ruminococcus_torques_group, Butyricoccus and Christensenellaceae_R-7_group abundances and decreasing Bacteroides, Prevotellaceae_UCG-001 and Megamonas abundances (at genus level), which are primarily associated with short-chain fatty acid production. Ovarian metabolomic analysis showed that the major metabolites altered by PE supplementation were mainly involved in follicular development, estrogen biosynthesis, anti-inflammatory and antioxidant properties. Moreover, changes in both the cecal microbiota (at genus level) and ovarian metabolites were strongly correlated with laying performance, antioxidant status, and immune function. In conclusion, PE supplementation improved laying performance in aged hens by enhancing antioxidant, immune, and ovarian functions, promoting follicular development and estrogen secretion, and modulating the gut microbiota and ovarian metabolites. These findings will offer novel insights into the mechanisms that underlie egg production in the ovaries of aged poultry. Full article