Search Results (3,429)

From an immunological perspective, infertility mechanisms encompass not only fertilization but also implantation, as well as both early and late pregnancy loss. Growing attention is being directed towards the influence of systemic disorders on reproductive outcomes. The immune system plays a fundamental and regulatory role in human reproduction. Immunological factors may affect multiple stages of this process, potentially justifying their inclusion in extended diagnostic pathways. The impact of autoimmunity and the presence of various antibodies on reproductive functions is discussed. Special attention is given to the immunomodulatory role of progesterone in reproduction and a state of impaired progesterone action—luteal deficiency. Endometriosis is also highlighted as a disorder both associated with infertility and underpinned by a strong immunological basis. The usefulness of assessing lymphocyte subpopulation balance, cytokine profiles, and Th1/Th2 immune response in the diagnostic work-up of infertility is addressed. Furthermore, the prospect for a role of local and systemic infections, subclinical inflammation and microbial colonization is shown. Tests applied in the evaluation of implantation and placental development disorders are discussed. Adequate immunological diagnostics and accurate identification of the underlying causes of infertility facilitate effective therapeutic strategies and can substantially increase the likelihood of achieving a successful pregnancy. Full article

This study takes the Jiangligou Plutonic Complex (JPC) in the Western Qinling tectonic belt as the research object and systematically investigates the crystallization age, magmatic genesis, and tectonic setting of the plutons. Results indicate that the Jiangligou Plutonic Complex was formed during the Triassic period (252–216 Ma, corresponding to the “Indosinian” regional tectonic stage in East Asia). Six plutons are recognized in the Jiangligou region. Plutons IV (246 ± 3 Ma) and V (252 ± 2 Ma) record Early Triassic magmatism, and Plutons I (238 ± 1 Ma), II (216 ± 2 Ma), III (216 ± 2 Ma), and VI (224 ± 2 Ma) correspond to Middle-Late Triassic magmatic activity. Furthermore, the data from this study indicate that a Th/U ratio > 0.4 serves as a more effective criterion for identifying reliable magmatic zircons. Our data indicate that the Jiangligou Plutonic Complex represents a multi-stage magmatic system generated in response to the tectonic evolution of the West Qinling, spanning from the late subduction of the Mianlue Ocean to the peak collision between the North China and Yangtze blocks during the Indosinian orogeny. The region is dominated by a collisional setting, with magmas primarily derived from crustal remelting. This study provides key chronological and geochemical constraints on the Indosinian tectonic–magmatic evolution of West Qinling. Full article

Introduction: Atopic dermatitis (AD) is driven by complex pathways that mediate inflammation and pruritus. The pathophysiology of AD’s disease involves multiple pathways. Interleukin-13 (IL-13) is considered a major cytokine in Th2-type inflammation, responsible for changing the epidermal barrier and producing chronic inflammation, whereas interleukin-31 (IL-31) is considered a major inducer of pruritus. The exact correlation of each of these cytokines with disease severity in children with AD appears to vary across studies. This study was therefore designed to evaluate whether IL-13 and IL-31 levels contribute complementarily or independently to the overall clinical severity of AD in the Moroccan pediatric population and to analyze the correlation between serum IL-13 and IL-31 levels and investigate their correlation with disease severity in a pediatric cohort. Methods: A total of 52 children with moderate to severe AD were included. The severity of the disease was measured using the SCORing Atopic Dermatitis (SCORAD) index. Serum levels of IL-13 and IL-31 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Results: The IL-13 serum level showed a considerable positive correlation with the SCORAD score (r_s = 0.7, p < 0.0001). On the other hand, IL-31 levels revealed no correlation with SCORAD (r_s = 0.07, p = 0.62) but were positively correlated with pruritus intensity (r_s = 0.91, p < 0.001). Conclusion: Our results support the presence of different pathophysiological axes in pediatric AD, where IL-13 functions as a reliable biomarker of inflammatory severity. IL-31 acts as a systemic marker of the pruritic pathway. Full article

Vaccination remains a cornerstone of livestock disease control, yet its effectiveness under field conditions is often compromised by concurrent infections, particularly parasitic helminths. This review explores how infections shape vaccine-induced immunity in cattle, emphasizing the immunoregulatory mechanisms by which helminths interfere with protective responses. Chronic infections with Fasciola hepatica and Ostertagia ostertagi induce Th2-biased and regulatory immune environments that suppress antigen presentation, cytokine production, and memory formation and maintenance, leading to reduced vaccine efficacy. Evidence from experimental and field studies is scarce and constitutes a gap in our knowledge on how vaccines work in the field. Available data indicate that infection timing, intensity, and chronicity critically determine the extent of vaccine interference. The review highlights diagnostic approaches that can support targeted deworming before vaccination and proposes integrated management strategies combining parasite control, immunization, and nutritional optimization. Such approaches can mitigate helminth-driven immune suppression, enhance herd protection, and reduce dependence on anthelmintics. However, the impact of helminth infections on vaccine efficacy in cattle should be further assessed in the field. Understanding parasite–vaccine interactions is essential to refine vaccination programs, guide the development of next-generation vaccines, and promote sustainable livestock health in parasite-endemic areas. Full article

The 2025 Ebola outbreak that ravaged the Bulape Health District (HD) in Kasai, Democratic Republic of Congo (DRC), was tackled using the incident management system (IMS) model. The Bulape HD is located in the Mweka territory, which has experienced two Ebola epidemics: one in 2007 and another in 2008. The IMS comprises seven strategies recommended for an effective response to an Ebola outbreak: (i) thorough investigation, (ii) strengthening infection prevention and control measures in the community, (iii) ensuring that medical care is provided by experienced professionals, (iv) strengthening risk communication and community engagement (RCCE), (v) ring vaccination, (vi) operational research, and (vii) anchoring interventions in the existing health system. We share our experience implementing these seven strategies and compare them with those utilized during three previous Ebola outbreaks. This paper describes our achievements, the resulting benefits, and the factors that facilitated the implementation of the aforementioned strategies. A literature review and interviews were conducted. The atlas.ti 22 software was used for data analysis. Implementing these seven strategies contributed to an effective response, largely due to the experience and expertise of those involved but also thanks to the support of technical and financial partners (TFPs) and the engagement of the local community. Challenges such as geographical accessibility, the fragile health system, the community’s strong attachment to traditional practices, and negative reactions to healthcare—which was widely discredited, with many of those involved expressing a lack of faith in its effectiveness—were major obstacles. To overcome these challenges, an integrated approach was utilized, combining a rapid comprehensive response with deep and respectful community engagement. The support and alignment of TFPs were invaluable during this process. The RCCE pillar proved key to successful IMS implementation. Our experiences will be useful during the next Ebola outbreak in the DRC; additionally, they may also help to inform the response to similar outbreaks in other countries. Full article

The neuroendocrine and immune systems interact bidirectionally through shared ligands and receptors during inflammation, thereby regulating immune responses. Leptin, primarily known for its role in energy metabolism and appetite regulation, also modulates neuroinflammatory pathways. Its receptors are widely expressed on immune cells and contribute to immune mechanisms implicated in the pathogenesis of neuroinflammatory disorders such as multiple sclerosis (MS) and Alzheimer’s disease (AD). This review highlights recent advances in understanding leptin’s role in immune regulation, with a focus on its impact on MS and AD. A comprehensive literature review was conducted until October 2025, using PubMed, Google Scholar, and Scopus to identify studies investigating leptin in neuroinflammatory conditions, particularly MS and AD. Leptin exerts broad immunomodulatory effects by activating T cells, dendritic cells, and microglia, and promoting their proliferation and phagocytosis. Its elevation enhances Th1 and Th17 responses, drives pro-inflammatory macrophage phenotype polarization, and suppresses regulatory T cell and Th2 responses, immune pathways involved in MS. Peripheral leptin levels are increased in MS, especially during disease exacerbations. In contrast, in AD, they are typically reduced, particularly in patients with normal body mass index (BMI), where their decline contributes to amyloid-β and tau pathology. These divergent patterns position leptin as a bidirectional regulator at the intersection of immunity and neurodegeneration. Additionally, its protective or detrimental effects likely depend on whether it acts under physiological conditions or in the context of obesity-induced leptin resistance. Elevated leptin levels in obesity exacerbate inflammation and diminish its neuroprotective effects. In conclusion, leptin is elevated in MS patients but downregulated in AD, reflecting its bidirectional effects. In leptin resistance, peripheral proinflammatory signaling is maintained while central leptin signaling is restricted, thereby potentially promoting autoimmunity in MS and limiting neuroprotection in AD. Further mechanistic and longitudinal studies are needed to clarify the relationship between leptin dysregulation, leptin resistance, neuroinflammatory and neurodegenerative diseases. Full article

Tuberculosis (TB) has various clinical presentations; pulmonary TB (PTB) affects only the lungs, whereas extrapulmonary TB involves other organs, including pleural TB (PLTB). Immunological studies of patients with extrapulmonary TB primarily focus on the cellular Th1 response, which produces key cytokines, including IFN-γ, TNF, IL-12, and IL-6. TNF and IL-6 play functional roles in host resistance to Mycobacterium tuberculosis (Mtb) infection. Findings suggest that TNF facilitates macrophage containment of Mtb, whereas IL-6 increases macrophage apoptosis induced by Mtb. Studies of the human genome have identified single-nucleotide polymorphisms (SNPs) in genes encoding cytokines associated with TB susceptibility. This study aimed to assess the potential of the IL6-174G/C (rs1800795), TNF-308G/A (rs1800629), and TNF-238G/A (rs361525) SNPs as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. A total of 269 individuals were included: 69 patients with PLTB and 200 healthy individuals. The IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms were determined by sequence-specific primer polymerase chain reaction (SSP-PCR). Results showed significantly higher frequencies of the G/C, G/A, and G/A genotypes in patients with PLTB (94.0%, 94.2%, and 83.3%) than in controls (40.0%, 19.0%, and 13.4%) for the IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms, respectively. Logistic regression analysis showed significant associations between the G/C, G/A, and G/A genotypes and susceptibility to PLTB. The IL6-174G/C, TNF-308G/A, and TNF-238G/A gene polymorphisms may serve as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. Full article

Background/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization’s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular/nasal prime-boost regimen, the vaccine elicited a mixed Th1/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control. Full article

Background: Tuberculosis (TB) remains a pressing global health crisis. The inadequate efficacy of the BCG vaccine against adult pulmonary TB underscores the urgent need for novel, effective vaccines. This study aimed to design a novel mRNA vaccine candidate against TB using a rational immunoinformatics approach. Methods: From 13 antigens, >12,000 epitopes were filtered to select 60 optimal peptides (36 CTL, 16 HTL, 8 B-cell), assembled into 25 scaffolds with 49 TLR2/4 agonist configurations. EP9158H underwent structural modeling, 100 ns molecular dynamics, docking, immune simulation, RNAfold, and conservation analysis across 76 strains. Results: EP9158H, encoding 15 CTL, 9 HTL, and 8 B-cell epitopes flanked by TLR2 agonist ESAT-6 and TLR4 agonist HBHA, emerged as the optimal candidate. All 32 constituent epitopes showed >81% conservation, with 81.25% exhibiting perfect identity across MTBC lineages. The scaffold demonstrated high solubility (0.531), broad population coverage (73.76% MHC-I, 88.91% MHC-II), optimal TLR2/4 docking scores (−1359.7 and −1348.3), and robust structural stability (ProSA Z-score −6.18; RMSD 22–27 Å). Immune simulation predicted strong Th1-biased T-cell responses and high levels of antibody titers. RNAfold analysis revealed stable mRNA secondary structures (MFE −1127.5 kcal/mol) supporting efficient translation. Conclusions: EP9158H integrates broad epitope coverage, dual TLR agonism, and validated stability. Compared to single-antigen vaccines, it offers superior strain coverage, enhanced innate activation, and mRNA advantages for CTL induction, warranting experimental validation. Full article

The U.S. municipal solid waste recycling rate has remained near 32% for two decades, placing the country 30th globally. In response, the U.S. Environmental Protection Agency (EPA) has set a national goal of achieving a 50% recycling rate by 2030, yet concrete strategies for reaching this target remain limited. Persistent challenges—such as low public participation and inadequate dissemination of effective practices—highlight the potential importance of recycling education. This study has two aims. First, we assess federal investment in recycling education through the EPA’s Environmental Education Grants Program (1992–2023) using a large language model (LLM)-assisted text-mining approach to identify recycling-focused projects. Second, we examine the factors that shape state-level recycling rates, including policy, demographic, infrastructure, and education variables. Our results show that states with bottle bills—deposit–refund laws for beverage containers—and states with higher levels of educational attainment exhibit significantly higher recycling rates. By contrast, federal investments in recycling education, as measured through the grants program, were not statistically associated with state-level recycling performance. This study introduces a novel analytic approach for evaluating how policy and educational factors contribute to state-level recycling outcomes and to national recycling performance. Full article

Rear-end collisions remain a significant category of road accidents, despite widespread passive safety systems. Although modern seats are designed to reduce injury risk, the influence of accessory lumbar supports on passenger safety is still insufficiently investigated. This study analyzes the biomechanical response of a Hybrid III 50th percentile dummy on a vehicle seat fitted with various lumbar support types, compared to a reference configuration. Tests were conducted on a sled bench, simulating impacts of varying energy using crash pulses of 10 g, 15 g, and 20 g, for each tested lumbar support configuration in carefully controlled laboratory conditions. A key element of the procedure was analyzing changes in head and chest acceleration waveforms relative to results obtained for the reference seat. To quantitatively assess discrepancies between signals, the Root Mean Square Error (RMSE) and the CORA (CORrelation and Analysis) objective rating method were applied. These tools enabled precise separation of amplitude changes from phase shifts arising from different system dynamics. The results show that additional equipment elements modify dummy–seat interaction, with the extent of biomechanical response changes also depending on crash pulse value. This indicates that ergonomic supports are not biomechanically neutral and should be considered in comprehensive safety analyses. Full article

Background/Objectives: Postoperative cognitive dysfunction (POCD) is a serious complication of anaesthesia/surgery. The present study investigated the effects of nicardipine—a calcium channel blocker—on neuroinflammation and POCD in rats. Methods: Following ethical approval, 30 Wistar albino rats were divided into three groups: control (Group C), surgery (Group S), and surgery and nicardipine (a single intraperitoneal dose of 5 mg/kg nicardipine) (Group N). Cognitive function was assessed 48 h postoperatively using the MWM test. The rats were sacrificed on the 5th day, and hippocampi were isolated and frozen at −80 °C on the same d ay. Hippocampal tissues were homogenised; ELISA and Western blot tests were performed to assess IL-1, IL-6, TNF-α, and caspase-3. Results: All groups showed a significant decrease in the time required to locate the hidden platform from day 1 to day 4. In the probe trial of the Morris water maze test, Group C spent more time in the target quadrant compared with Group S, indicating surgery-related cognitive impairment. The ELISA and Western blot analyses demonstrated that the hippocampal levels of IL-1, IL-6, TNF-α, and caspase-3 were significantly elevated in both Groups S and N compared with the controls. No statistically significant differences were observed between Groups S and N, indicating that the measured cognitive performance and hippocampal inflammatory responses were comparable between these groups. Conclusions: This study showed that a single intraperitoneal dose of 5 mg/kg of nicardipine did not measurably improve early postoperative cognitive performance or reduce hippocampal inflammation. In particular, nicardipine did not have a detectable effect on early postoperative neuroinflammation or cognition at the tested dose and timing in this rat model. Further studies exploring different doses and timing or repeated administration would help to clarify its potential role. Full article

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide. While immune checkpoint blockade (ICB) has transformed cancer therapy, its clinical benefit in CRC is often limited by an immune-excluded tumor microenvironment (TME). MicroRNA-21-5p (miR-21-5p) is a well-established oncomiR in CRC; however, its role in immune resistance remains incompletely elucidated. In this study, we explored the potential immunoregulatory role of miR-21-5p in CRC by integrating transcriptomic profiling of TCGA-COAD and TCGA-READ cohorts with experimental validation of its target PTEN in CRC cell models. MiR-21-5p was markedly upregulated in tumors compared with adjacent normal tissues and was associated with reduced infiltration of CD8⁺ T cells and dendritic cells. Functional assays confirmed that miR-21-5p directly targets PTEN; transcriptomic correlations further suggested potential links to PI3K/AKT activation and alterations in JAK–STAT and Th17-associated signaling. Elevated miR-21-5p was associated with transcriptomic signatures indicative of altered Th1/Th2 balance, reduced IgA-related immune responses, and features of an immune-excluded TME. Therapeutically, the inhibition of miR-21-5p has been reported in previous studies to restore PTEN and modulate signaling pathways. However, our study did not evaluate immune reactivation or checkpoint-blockade efficacy; thus, such therapeutic implications remain hypothetical. Collectively, these findings suggest that the miR-21–PTEN–PI3K/AKT axis may contribute to shaping immune-related features in CRC. These findings provide a rationale for future studies investigating whether targeting miR-21-5p could enhance antitumor immunity or improve immunotherapy response in CRC. Full article

This research focuses on the additional valorization of olive leaves, a by-product of regular olive pruning, by increasing their secondary metabolite content through the combined application of biochar and a phenolic extract from olive leaves. A suspension of biochar, obtained by the pyrolysis of grapevine pruning residues, was prepared by mixing it in demineralized water (1.5 g; 5 L; 24 h). The phenolic extract was obtained by extracting lyophilized and ground olive leaves in demineralized water (50 g; 5 L; 24 h), while the combined preparation was obtained in an analogous manner (1.5 g biochar; 50 g olive leaf powder; 5 L water; 24 h). Treatments were applied at the beginning of July, 50 days after anthesis (May 16th) and included the following: (i) control treatment (demineralized water), (ii) biochar solution, (iii) phenolic extract solution, and (iv) a combined aqueous preparation of biochar and phenolic extract, all with the addition of a wetting agent. Trees of the olive cultivars Leccino and Istarska bjelica were sprayed with the corresponding preparation until runoff. Olive leaves were sampled three weeks after treatment (July 26th) and, after washing and drying, and were prepared for LC-MSMS analysis. Both biochar-based treatments induced the most potent effects, although responses differed between cultivars. In particular, apigenin derivatives, hydroxytyrosol, luteolin-7-rutinoside, and the secoiridoid oleacein showed apparent differences between biochar treatments and the control. Overall, higher concentrations of the sum of detected secoiridoids were observed in the leaf samples of ‘Istarska bjelica’ under BCH and BCH+PH treatments, whereas no such differences were found for ‘Leccino’ cultivar. Further research is needed to clarify the cultivar-dependent response of secondary metabolism in these olive cultivars and the mechanisms by which biochar foliar application modulates metabolite profiles. Full article

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic bacteria that can result in severe liver abscesses, pulmonary damage, and potentially fatal outcomes. Research has demonstrated that the outer membrane vesicles (OMVs) released by it can provide significant protection to infected animals and may serve as a promising candidate antigen for the development of a novel vaccine. Nevertheless, the specific mechanisms through which OMVs mitigate the detrimental effects of K. pneumoniae infection by promoting the polarization pathways of macrophages and T helper cells (Th cells) remain poorly understood. In this study, we first confirmed that Klebsiella pneumoniae outer membrane vesicles (K. pneumoniae_OMVs) were protective in K. pneumoniae-infected mice, and then we investigated the protective mechanisms by transcriptome data analysis. Then, we constructed a model of in vitro macrophage polarization, an in vivo model for Th differentiation, and a K. pneumoniae infection model in K. pneumoniae_OMVs-immunized mice. qRT-PCR, IHC, Western blotting, and ELISA were used to confirm the polarization indicators. The results showed that K. pneumoniae_OMVs were able to provide specific protection for mice with a maximum protection rate of 80%. In addition, the results of a transcriptome analysis suggested that the protective mechanism might be related to Th cells and macrophage polarization. Mice immunized with K. pneumoniae_OMVs were able to achieve rapid bacterial clearance after K. pneumoniae infection through an M1/Th1 immune response. Subsequently, tissue repair was accomplished through Th2/M2 immune response in the late stage of K. pneumoniae infection to avoid causing inflammatory damage. This study offers a theoretical foundation for the K. pneumoniae_OMVs vaccine’s actual application. Full article