搜索结果：Molecular immunology

Neutrophil extracellular traps (NETs) are increasingly recognized as critical mediators in vascular inflammation and remodeling, yet their molecular mechanisms in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis remain largely unexplored. This study employed integrated bioinformatics approaches and experimental validation to identify NETs-related biomarkers in IPAH. We performed weighted gene co-expression network analysis (WGCNA) on merged transcriptomic datasets (GSE117261 and GSE48149, comprising 40 IPAH and 34 control samples), identifying a blue module significantly correlated with IPAH status. By intersecting module genes with 69 known NETs-related genes, we obtained 19 differentially expressed NETs-related genes (DE-NRGs) enriched in neutrophil degranulation, interleukin-6 regulation, and NETs formation pathways. Three complementary machine learning algorithms converged on five key biomarkers: CSF3R, MGAM, ITGAM, TLR8 (downregulated), and SELP (upregulated). These biomarkers demonstrated strong diagnostic performance in an independent validation cohort, with an area under the curve greater than 0.8. Immune infiltration analysis revealed significantly decreased neutrophils, macrophages, and myeloid-derived suppressor cells in IPAH patients. Single-cell RNA sequencing validated cell-type-specific expression patterns, with CSF3R predominantly in neutrophils, ITGAM/TLR8 in macrophages, and SELP in endothelial cells. Critically, monocrotaline-induced rat pulmonary arterial hypertension model confirmed significant downregulation of MGAM, CSF3R and ITGAM at protein levels. Our findings establish a NETs-related molecular signature for IPAH diagnosis and reveal impaired neutrophil function as a key pathogenic mechanism in IPAH, providing novel molecular targets for therapeutic intervention and risk stratification.

Inborn errors of immunity (IEIs) are an expanding group of genetically defined disorders associated with infections, autoimmunity, and malignancy. Advances in high- throughput genomics and updates to international classifications have reformed the field, shifting from phenotype-based descriptions to molecular frameworks. Bibliometric analysis offers a structured approach to mapping research growth, collaboration, and thematic evolution. We analyzed global IEI research from 1995 to 2025 using bibliometric methods, focusing on publication trends, collaboration networks, leading contributors, and thematic shifts. Publications were retrieved from Web of Science Core Collection and PubMed. After screening, 840 original articles were analyzed with Biblioshiny and VOSviewer to assess citation patterns, coauthorship, thematic clusters, and keyword evolution. IEI research (n = 840; 333 journals; 7,466 authors) increased at 4.5% annually, with a marked rise after 2018 after next-generation sequencing and International Union of Immunologic Societies classification updates. The United States produced the largest output, while European countries had a higher citation impact per article. Collaboration was strongest between North America and Europe, with other regions remaining more domestically focused. Thematic mapping revealed a transition from clinical phenotypes to genetic, multiomic, and precision frameworks, alongside growing focuses on autoinflammation, immune dysregulation, and rare disease subgroups. Over 3 decades, IEI research has expanded substantially, reflecting a paradigm shift toward molecular discovery and international collaboration. Persistent regional disparities highlight the need for inclusive genomic studies and equitable partnerships, providing strategic insights to advance clinical immunology and enhance care for patients with rare immune disorders.

Triple-negative breast cancer (TNBC) presents a poorer prognosis than other breast cancer subtypes, attributed to its aggressive nature and the lack of specific therapeutic interventions. TNBC has high recurrence rates and limited survival despite current therapies, emphasizing the critical need for improved treatment options. TNBC exhibits increased levels of LRP6 expression, which is linked to tumor-related features such as growth, metastasis, poor prognosis, resistance to chemotherapy, and invasion. Therefore, LRP6 offers a promising option for therapeutic intervention in breast cancer. This research aims to use in silico and bioinformatics techniques to develop an mRNA vaccine that specifically targets the LRP6 antigen. The final vaccine construct comprised 431 amino acids, with a molecular weight of 47.5 kDa, theoretical pI of 5.11, and an instability index of 38.3 indicating stability. Population coverage analysis showed broad global coverage of 99.04%. Molecular docking revealed strong binding affinities to immune receptors, including HLA-A0201 (-812.0), HLA-A0301 (-707.1), HLA-DRB1*0101 (-955.7), and TLR9 (-1339.5). Immune simulation predicted high titers of IgG1 antibodies, sustained memory B cell populations (> 200 by Day 365), elevated CD4+ T cells (> 3000), and robust IFN-γ responses. Codon optimization yielded a high CAI value of 0.94 and GC content of 58.37%, supporting efficient expression in human systems. Collectively, these results suggest that the designed LRP6-targeted mRNA vaccine could induce durable humoral and cellular immunity against TNBC and warrants further experimental validation.

EP400 N-terminal Like (EP400NL) is a recently characterized transcriptional coactivator implicated in chromatin remodeling and oncogenic signaling. Although its precise function remains incompletely understood, emerging evidence suggests that EP400NL contributes to transcriptional regulatory networks relevant to tumor progression. In this study, we investigated the structural and functional properties of the C-terminal domain (CTD) of EP400NL using bioinformatic and molecular modeling approaches and evaluated the anticancer potential of a peptide derived from this region. Molecular dynamics simulations indicated that the CTD forms an extended, flexible tail that may serve as a functional motif mediating protein-protein interactions. Cell-based assays demonstrated that delivery of the EP400NL CTD peptide or shRNA-mediated targeting of the corresponding RNA region suppresses cancer cell proliferation and clonogenicity, supporting a potential inhibitory role of this domain in tumor growth and survival. Collectively, these findings identify the EP400NL CTD as a promising structural motif for anticancer peptide development.

Epididymitis is a common urogenital infection in adult men caused by sexually transmitted pathogens, urinary tract infections, trauma, or autoimmune mechanisms, with etiologies varying by age. In addition to severe pain and reduced quality of life, it may result in complications such as abscess formation, testicular atrophy, and infertility. Despite its clinical significance, comprehensive analyses of research trends remain limited. Bibliometric and knowledge-mapping approaches can provide quantitative insights into the field's development and hotspots. Using the Web of Science Core Collection and the PubMed Database, we retrieved literature related to epididymitis published from January 1, 2014, to September 10, 2025. Bibliometric analyses of publication volume, journals, authors, institutions, countries, and keywords were conducted using the Bibliometrix R package (v5.1.1), VOSviewer (v1.6.20), and CiteSpace (v6.4. R2). Scientific knowledge maps were generated to identify research hotspots and developmental trends in epididymitis. A total of 497 publications from 2,887 authors across 955 institutions in 67 countries were analyzed. Annual output remained stable at 30-50 articles since 2014. Andrologia was the most influential journal, and Pilatz Adrian was the leading author. China produced the most publications, the United States had the highest total citations, and Germany showed the highest average citation impact and strongest international collaboration. Justus Liebig University Giessen ranked first among institutions. Research trends have shifted from clinical diagnosis toward pathogenic and immunological mechanisms. Human studies focus on clinical features and treatment outcomes, whereas animal studies emphasize immunoinflammatory mechanisms and reproductive impacts. Research on epididymitis is advancing from clinical observation toward molecular immunology and precision therapy. Future studies should further focus on sexually transmitted pathogens, the immunopathological mechanisms of epididymitis, and the relationship between chronic inflammation and male infertility.

Lupus panniculitis (LP) is a neglected, often treatment-refractory subtype of cutaneous lupus erythematosus. It is characterized by inflammation of subcutaneous adipose tissue, and the pathomechanisms are poorly understood. We sought to explore the cellular and molecular signatures of LP and their relationship to systemic lupus erythematosus. We performed imaging mass cytometry (IMC; LP n = 8, Healthy Control (HC) n = 6) and targeted transcript profiling by NanoString nCounter (Human Immunology Panel, 579 genes; LP n = 9, HC n = 9). LP lesions showed extensive septal leukocyte infiltration. The infiltrate consisted predominantly of T cells (48%), followed by B cells (14%) and antigen-presenting cells (APCs). T cells exhibited a cytotoxic (CD8+, GranzymeB+) and skin-homing (CLA+) phenotype, with upregulation of Th1 markers. They closely interacted with M1 macrophages. B cells displayed strong spatial interactions with naïve T cells. NanoString analyses revealed upregulation of T- and B-cell receptor signaling pathway genes, antigen presentation-related genes (MHC-I/II), and Th1 associated programs (STAT1/IRF1), together with activation of innate immune, complement, and pattern-recognition receptor pathways. This was paralleled by strong upregulation of IDO1, a key enzyme in tryptophan metabolism, and inversely correlated, reduced AHR expression. Our data provide new pathomechanistic insights into LP, highlighting overlaps with systemic lupus, but also LP-specific features. This may pave the way for adopting more targeted treatment approaches for LP.

Planarians display remarkable resistance to bacterial infection, including infection by Staphylococcus aureus, yet the molecular mechanisms underlying this antibacterial capacity remain poorly defined. Histones are highly conserved chromatin-associated proteins traditionally known for their structural role in nucleosome organization; however, studies in diverse organisms have revealed that histones can function as antimicrobial effectors when released extracellularly. Whether histone proteins contribute to antibacterial defense in planarians has not been investigated. Here, we identified core histone proteins (H1/H5, H2A, H2B, H3, and H4) from the transcriptome of Schmidtea mediterranea through comparative sequence analysis using reference histones from Homo sapiens, Drosophila melanogaster, and Caenorhabditis elegans. Domain architecture and phylogenetic analyses confirmed their evolutionary conservation. Core histones were isolated from planarian nuclei by acid extraction and validated by SDS-PAGE and immunoblotting. Functional assays revealed that histone-enriched extracts isolated from planarian nuclei exhibit selective and dose-dependent antibacterial activity against Gram-positive bacteria, with the strongest inhibition observed for S. aureus, whereas minimal effects were detected against Gram-negative species such as Escherichia coli. Histone treatment induced membrane permeability and bacterial death, as demonstrated by SYTO9/propidium iodide staining and confocal microscopy. Importantly, protease treatment and heat denaturation abolished antibacterial activity, confirming that the effect depends on intact protein structure. Collectively, our findings demonstrate that histone-enriched chromatin extracts from S. mediterranea possess intrinsic antibacterial activity with preferential efficacy against Gram-positive bacteria, supporting a model in which chromatin-derived histone proteins represent conserved components of innate immune defense in planarians.

Hepatocellular carcinoma (HCC) is characterized by a highly immunosuppressive microenvironment, which contributes to its unfavorable clinical outcomes. Myeloid-derived suppressor cells (MDSCs) play a crucial role in this process. Schisandrin B (SchB) shows anti-tumor potential, but its mechanism in suppressing MDSCs remains unclear. This study investigates how SchB inhibits MDSCs accumulation and enhances anti-PD-1 therapy efficacy in HCC.SchB's efficacy and mechanism were investigated both in vitro and in vivo. In vitro, MTT, wound healing, EdU, colony formation, flow cytometry, ELISA, western blot, immunofluorescence, Co-IP, molecular dynamics (MD), and CETSA assays were employed to evaluate the therapeutic effects and mechanistic action of SchB on HCC. In vivo, a mouse HCC xenograft model was used to evaluate whether SchB could enhance the anti-tumor effect of PD-1 mAb and the potential mechanism.Mechanistically, SchB suppressed TRIM27 expression, disrupted the interaction between TRIM27 and STING, and enhanced STING/TBK1/IRF3 signaling, thereby suppressing the secretion of IL-6 and GM-CSF as well as the accumulation of MDSCs. SchB could directly bind to TRIM27 and downregulate its expression, thereby enhancing STING protein stability. In vivo, SchB effectively reduced MDSCs accumulation while promoting T cell recruitment, thereby augmenting the antitumor efficacy of PD-1 mAb therapy.SchB up-regulates STING by suppressing TRIM27, inhibits IL-6/GM-CSF secretion, and reduces MDSCs accumulation, indicating that SchB has the potential to be a promising candidate for PD-1 inhibitor therapy in HCC.

The persistent global burden of tuberculosis (TB) and the context-dependent efficacy of the Bacillus Calmette-Guérin (BCG) vaccine necessitate the development of innovative prophylactic strategies. mRNA vaccine platforms have emerged as a transformative toolkit, offering unprecedented versatility in antigen design and manufacturing scalability. This inclusive innovation review synthesizes the molecular engineering and immunological mechanisms of mRNA TB vaccines, evaluating their capacity to address the unique challenges posed by the intracellular lifestyle of Mycobacterium tuberculosis (Mtb). mRNA platforms realistically offer superior endogenous antigen production for CD8⁺ T-cell activation and the flexibility to encode multi-stage fusion antigens targeting both active and latent bacilli. However, significant constraints remain; mRNA technology alone cannot resolve the spatial sequestration of Mtb within necrotic granulomas or the "recruitment lag" of systemic immunity to the lung parenchyma. Achieving sterile protection requires a transition toward mucosal delivery systems capable of inducing lung TRM cells. Furthermore, translational success must be measured beyond classical interferon-gamma (IFN-γ) readouts, prioritizing correlates of protection that reflect site-specific immunity, safety in latently infected populations, and the deployment of thermostable formulations in endemic regions. By integrating mRNA constructs into heterologous prime-boost regimens and host-directed therapies, the field moves toward a precision vaccinology framework capable of curtailing the TB epidemic.

Inflammation, as a critical defensive response of the body, can exacerbate tissue damage through oxidative cascade reactions when it becomes uncontrolled. Among the key oxidative stress mediators are monoamine oxidase A (MAO-A) and peroxynitrite (ONOO-), which synergistically promote cellular damage. To further elucidate their molecular mechanisms of action, precise and reliable imaging tools are required for spatiotemporal dynamic monitoring of both mediators. Addressing the limitations of traditional dual-probe detection, which suffers from inconsistencies in distribution and response, this study developed a mitochondria-targeted dual-responsive fluorescent probe, KMO, achieving the first in situ real-time visualization of MAO-A and ONOO- in inflammatory cells and an acute hepatitis mouse model. Utilizing this tool, we revealed a self-amplifying cycle in inflammation characterized by "MAO-A activation─ONOO- burst─ferroptosis─inflammation exacerbation", and demonstrated that inhibiting ferroptosis can disrupt this pathway. This work not only provides a fluorescent imaging tool but also establishes a theoretical and experimental foundation for elucidating the mechanisms of acute inflammation and targeted interventions.

Asthma is a chronic inflammatory disease driven by dysregulated immune responses and mast cell activation. While corticosteroids remain the primary treatment, their long-term use is associated with adverse effects, necessitating safer alternatives. This study aims to evaluate the therapeutic potential and underlying mechanisms of Chamaecrista nomame (CN) extract and its active compound luteolin in allergic asthma. We performed bioactivity-guided fractionation to identify active compounds from CN extract. An ovalbumin-induced murine asthma model was utilized to investigate the efficacy of CN in vivo. Transcriptomic analysis of bone marrow-derived mast cells was conducted to elucidate molecular pathways regulated by luteolin. Additionally, cytokine release assays were performed using house dust mite-stimulated human peripheral blood mononuclear cells (PBMCs). CN extract demonstrated potent anti-allergic effects by significantly inhibiting mast cell degranulation and inflammatory mediator release. Luteolin was identified as the primary active compound, modulating FcεRI-mediated signaling in mast cells. In the murine asthma model, CN markedly reduced airway inflammation, mucus hypersecretion, and immune cell infiltration, with efficacy comparable to corticosteroids. Transcriptomic data indicated that luteolin suppresses proinflammatory cytokine production by downregulating NF-κB and MAPK signaling pathways. Moreover, CN and luteolin significantly inhibited cytokine release from house dust mite-stimulated human PBMCs, highlighting clinical relevance. These findings suggest that CN and luteolin may serve as promising natural therapeutic agents for allergic asthma, offering a potential alternative to conventional treatments.

This laboratory protocol describes a fully standardized and integrated diagnostic workflow for the detection of major sexually transmitted infections (STIs), including HIV-1/2, Treponema pallidum, hepatitis B virus (HBV), hepatitis C virus (HCV), Chlamydia trachomatis, and HSV-2. The workflow combines rapid immunochromatographic tests, non-treponemal and treponemal assays, hemagglutination testing, and ELISA-based antibody and antigen detection into a coherent algorithm. The protocol is aligned with ISO 15189 and Clinical and Laboratory Standards Institute (CLSI) recommendations and is specifically designed to be feasible in resource-limited laboratories. It includes detailed pre-analytical requirements for blood collection, transport, and storage; standardized step-by-step procedures for each assay; internal and external quality assurance components; troubleshooting guidance; and recommendations for data management and sample traceability. This integrated approach aims to optimize diagnostic yield, ensure reproducibility, and support large-scale epidemiological studies or routine diagnostic activities in low-income settings where access to molecular testing is limited.

It is commonly assumed that aging and chronic low-grade inflammation compromise adaptive immunity, particularly the function and metabolism of CD4+ T cells. The preceding are key regulators of immune responses. These immunological alterations contribute to increased susceptibility to infections, diminished vaccine efficacy and the progression of age-related diseases. In contrast, adolescence and young adulthood tend to be characterized by more robust immune responses, though these are heavily influenced by modifiable lifestyle factors such as habitual physical activity, level of cardiorespiratory fitness, diet and body adiposity. Emerging evidence suggests that sustained physical activity throughout life may preserve CD4+ T cell competence by favourably modulating their metabolic programming. The current narrative review explores how lifelong physical exercise impacts CD4+ T cell metabolism, with particular emphasis on the developmental window of adolescence and the long-term benefits of early and sustained physical training across the lifespan. Molecular mechanisms linking exercise to metabolic reprogramming of T cells were summarised in parallel with attenuation of immunosenescence and inflammation over the lifespan. This review suggests that lifelong exercise may reprogram CD4+ T cell metabolism, enhancing oxidative phosphorylation at rest and glycolytic control upon activation, thereby improving Th17/Treg balance, reducing chronic inflammation and enabling effective effector T cell responses. In this context, exercise initiated early in life may act as a critical modulator by promoting optimal immune function from childhood and establishing a functional peak that helps preserve immune competence during aging. Lifelong and early-life exercise may reprogram CD4+ T cell metabolism, strengthening immune balance and preserving immune function during aging.

Skin-homing cutaneous lymphocyte-associated antigen (CLA)-expressing T cells play a key role in the pathogenesis of atopic dermatitis (AD) and psoriasis (Ps). We aimed to characterize the transcriptomic and epigenetic profiles of circulating CD4+CLA+ and CD4+ naïve T cells from patients with AD and Ps to find shared and unique molecular signatures associated with the diseases. Circulating CD4+CLA+ and CD4+ naïve T cells were sorted from the peripheral blood mononuclear cells of patients with AD (n = 11), those with Ps (n = 10), and healthy individuals (n = 11), followed by assay for transposase-accessible chromatin sequencing (ATAC-seq) and mRNA sequencing and data analyses. Transcriptomic and epigenetic landscapes differed markedly between CD4+CLA+ and CD4+ naïve T cells. In both AD and Ps, transcriptomic alterations within these cell populations were substantial, whereas changes in chromatin accessibility were relatively modest. In CLA+ T cells, patients with AD and Ps exhibited altered expression of genes involved in T-cell activation, cell cycle, and JAK-STAT signaling. These effects were more pronounced in AD, while a stronger association with innate immune activation was seen in Ps. Notably, CD4+ naïve T cells also exhibited disease-associated transcriptomic changes in both AD and Ps, including alterations in the JAK-STAT pathway and changes in the expression of IL-2 receptor components. Epigenetic profiling further revealed disease-associated chromatin regions linked to transcription factors involved in immune regulation. Both CD4+CLA+ and CD4+ naïve T cells exhibit transcriptomic and epigenetic alterations in AD and Ps, suggesting the influence of the chronic inflammatory milieu leading to shared and disease-specific changes, including transcriptomic rewiring of the JAK-STAT pathway in both diseases.

Liver diseases pose a significant global health burden. This review systematically elucidates the crucial role of exercise as a non-pharmacological intervention in the prevention and treatment of various liver conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), viral hepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Exercise effectively delays disease progression and improves patients' quality of life through multi-targeted mechanisms, such as improving glucose and lipid metabolism, enhancing insulin sensitivity, regulating immune-inflammatory responses, inhibiting hepatic stellate cell activation, and remodeling the tumor microenvironment. Future research should focus on developing individualized, precise exercise prescriptions and further exploring its molecular mechanisms by integrating multi-omics technologies, thereby providing innovative strategies for the comprehensive management of liver diseases.

Endoplasmic reticulum stress (ERS), caused by excessive buildup of misfolded proteins in the ER lumen, has emerged as a major contributor to diabetes mellitus (type-1 and type-2; T1DM and T2DM), leading to β-cell dysfunction, insulin resistance, and related comorbidities. In this review, we aim to characterize the signal transduction pathways in normal versus diseased conditions and their impact on the development of insulin-dependent and insulin-independent diabetes. Evidence on ERS and diabetes were searched in MEDLINE and Google scholar databases using search strings that incorporated synonyms of ERS, diabetes, β-cell dysfunction and insulin resistance and their impact in disease progression. Our search was guided by the pertinent keywords as mentioned in the "keywords" section, that encompassed past twenty-five years of body of literature in this field as evident from Urano et al. 2000 till Sue et al. 2025. Our results and conclusion are the distillation of past two and half decades of scientific research dedicated towards understanding the biology of ERS dependent diabetes. The ERS-induced Unfolded Protein Response (UPR), comprising of three signaling cascades, is pivotal in either protecting against or contributing to the pathophysiology of T1DM and T2DM. Clinically, ERS manifests as insulin resistance, heightened inflammation, and β-cell destruction. Consequently, ERS effectors and proteins involved in the UPR pathways have become attractive targets for pharmacological investigation. We also review some of the protein biomarkers of ERS dependent diabetes and relevant in vivo/ex vivo models used in clinical versus preclinical settings, as well as the latest state-of-the-art targeted molecular and cellular therapies that are currently being tried for the diabetic patients.

Mouse mammary epithelial cells possess a remarkable ability to regenerate the entire mammary gland through precisely regulated differentiation, involving complex molecular, morphological, and functional changes. Here, we performed comprehensive transcriptomic profiling of HC11 mouse mammary epithelial cells undergoing lactogenic differentiation using RNA sequencing and integrative bioinformatics. We identified 566 differentially expressed genes, reflecting extensive transcriptional reprogramming and activation of biosynthetic, metabolic, and secretory programs. Strong up-regulation of terminal and lactogenic differentiation markers, including Wap, Csn2, Lpl, Cd36, Lalba, Btn1a1, Xdh, Gata3, and Cebpb, signified maturation into a secretory phenotype. Functional evaluation via gene set enrichment analysis revealed transcriptional enrichment of mTOR, prolactin, insulin, ErbB, and autophagy-associated pathways, consistent with anabolic readiness and terminal differentiation. Conversely, p53, Wnt, and FoxO pathways were down-regulated, marking a transition from proliferation to differentiation. Transcription factors (FoxO1, Zbtb16, and Srebf1) and epigenetic regulators (Gadd45a and Hist1h1e) exhibited dynamic changes, underscoring coordinated transcriptional and chromatin remodeling. Gene set enrichment and protein-protein interaction analyses identified 10 hub genes, Agt, Ccnd1, Igf1, Mki67, Myc, Calm4, Rasgrp1, Cd69, Il6, and Pecam1, as central drivers of differentiation. Clustering of uniquely regulated genes further implicated roles in milk synthesis, protease activity, and lineage stabilization. Together, these findings define a transcriptional framework for lactogenic differentiation in the HC11 cell line model and provide a basis for future mechanistic studies.

Long-term osseointegration of orthopedic implants mandates a successful interaction between implant surface and resident bone tissue cells, including osteoblasts and osteoclasts. Titanium, TiAl6V4, and Stainless steel are widely used implant biomaterials due to their high biocompatibility and mechanical strength. In this study, we systematically investigated the effects of polishing and laser-induced periodic surface structures (LIPSS) on osteogenic and osteoclastic differentiation across these materials. A correlative multi-modal approach was employed to capture complementary aspects of bone formation and resorption. Scanning electron microscopy (SEM) assessed cell morphology and extracellular matrix deposition, while energy-dispersive X-ray spectroscopy (EDX) quantified elemental composition associated with mineral deposition. Raman spectroscopy enabled molecular characterization of both mineral (phosphate/carbonate) and organic matrix components. These analyses were complemented by alkaline phosphatase (ALP) activity and osteogenic gene expression to evaluate early and late stages of osteoblast differentiation. In parallel, osteoclast responses were characterized using SEM and F-actin imaging for cytoskeletal organization and fusion, together with tartrate-resistant acid phosphatase (TRAP) activity and osteoclast-related gene expression to quantify osteoclast differentiation. Our results reveal a reciprocal relationship between osteoblast and osteoclast activity for higher laser fluence LIPSS. We demonstrate that laser-modified surfaces support better osseointegration by enhancing bone formation while mitigating bone resorption, with corroborating results from various analytical techniques. These findings suggest that LIPSS is a viable method to optimize implant surfaces for improved osseointegration.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) through Ixodes tick bites, presents diverse clinical manifestations and may lead to persistent symptoms. This review summarizes current knowledge on the pathogen-host interactions and immune responses. Early infection can be influenced by tick saliva, which suppresses local host defense and promotes spirochete survival, and by pattern recognition receptors activating proinflammatory cascades. Bbsl employs a variety of immune evasion strategies, notably impairing antigen presentation-through disruption of MHC II and IFN-γ pathways-and continuously varying surface antigens to hinder long-lasting antibody formation. Autophagy plays a central role in modulating inflammation and T helper 17 adaptive immune responses, representing an underappreciated mechanism potentially influencing disease outcome. Adaptive immunity in LB is characterized by robust but often dysregulated humoral and cellular responses, with transient germinal centers and enduring IgM production contributing to incomplete pathogen clearance. Persistent immune defects include impaired long-term B cell memory, suppressed T cell activation, and ongoing immunosuppression after pathogen clearance. Similar patterns are observed in other postinfectious fatigue syndromes. Despite advances, gaps remain in understanding mechanisms of Bbsl persistence and the immunopathology underlying chronic disease, challenging diagnosis and therapy. Emerging molecular and cellular approaches offer new avenues to address immunity, diagnostics, and prevention. A multidisciplinary effort will be needed to improve long-term patient outcomes in the evolving epidemiology of LB.