Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants raise concerns about decreased vaccine efficacy, vaccines continue to confer robust protection in humans, implying that immunity beyond neutralization contributes to vaccine efficacy. In addition to neutralization, antibodies can mediate various Fc-dependent effector functions, including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP) and antibody-dependent cellular cytotoxicity (ADCC). However, the specific role of each Fc-mediated effector function in contributing to COVID-19 disease attenuation in human remains unclear. To fully define the potential immune correlates of Fc-mediated effector functions, we comprehensively analysed the above Fc-mediated effector functions in two study cohorts. In the CoronaVac vaccinee cohort, individuals without breakthrough infection exhibited higher levels of ADCP and ADNP activities with a greater degree of cross-reactivity compared to those who had breakthrough infection. A predictive model was established incorporating ADNP activity and IgG titre, achieving an area under the curve (AUC) of 0.837. In the COVID-19 patient cohort, BA.5-specific ADCP and ADNP responses were significantly reduced in COVID-19 patients with fatal outcomes compared to milder outcomes. The prognostic model incorporating WT, BA.5, and XBB.1.5 spike-specific ADNP demonstrated effective predictive ability, achieving an AUC of 0.890. Meanwhile, transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients in the acute phases of infection highlighted remarkably upregulation of neutrophil activity and phagocytic function, further reinforcing the essential role of ADNP. Collectively, our findings underscored Fc-mediated effector activities, especially neutrophil phagocytosis, as significant antibody biomarkers for the risk of SARS-CoV-2 breakthrough infection and COVID-19 prognosis.

Exosomes (Exos), extracellular vesicles of endosomal origin, are a promising therapeutic platform for tissue regeneration. In the current study, an exosome-capturing scaffold (ECS) was designed to attract and anchor exosomes via electrostatic adherence followed by lipophilic interactions. Our findings demonstrate that local enrichment of exosomes in the ECS implanted into critical mandibular defects could significantly accelerate endogenous bone regeneration by enhancing vascularization at the defect site. Notably, neutrophil (PMN)-derived exosomes (PMN-Exos) were identified as the predominant exosome subtype among all captured exosomes. During endogenous bone regeneration, PMN-Exos promoted endogenous vascularization primarily by stimulating the proliferation of endothelial progenitor cells (EPCs), which play a pivotal role in the vasculogenesis of new blood vessels. Mechanistically, vascularization involved PMN-Exo-derived miR455-3p, which promotes EPC proliferation by targeting the Smad4 pathway. In conclusion, this study offers an ECS with broad application prospects for enhancing tissue regeneration by accelerating vascularization. The elucidation of underlying mechanisms paves the way for developing novel strategies to regenerate various tissues and organs.

Post-transplant immune rejection affects graft function. Interaction between neutrophil extracellular traps (NETs) with specific immune cells and the specific mechanism in liver transplantation were still unclear.

Clinical patients RNA-Seq results were used for GSEA and KEGG analysis. C57BL/6 and C3H mouse models and clinical samples were use to describe the disease phenotype characteristics through multiple immunofluorescence, flow cytometry and etc. Cell co-culture experiments were performed to clarify the mechanism pathway process.

RNA-Seq results analysis indicated that the NETs formation pathway was upregulated. Animal models confirmed that in liver transplant immune rejection status the formation of NETs in situ and peripheral cells increased and the level of cell-free DNA (cf-DNA) in peripheral cells increased. Reactive oxygen species (ROS) as a predisposing factor for NETs accumulated more in immune rejection status and NETs are rich in mitochondrial DNA (mtDNA). NETs promote dendritic cell maturation through STING-related pathways. NETs formation increases in patients with liver transplant immune rejection and is positively correlated with disease severity.

We found that NETs can regulate dendritic cell maturation through STING-related pathways after liver transplantation, which may ultimately promote the occurrence of liver transplant rejection, providing a new perspective for clinical diagnosis, treatment and prevention of liver transplant rejection.

Acute lung injury (ALI) in neonates presents a grave threat to infant health, characterized by a heightened risk of mortality. Phillyrin, an extraordinary constituent derived from a traditional Chinese medicinal herb Forsythia suspensa, has garnered considerable attention for its pronounced anti-inflammatory properties. However, its therapeutic potential for acute inflammatory diseases in neonates remains unclear. Therefore, our current study endeavors to assess the protective effects of phillyrin against lipopolysaccharide (LPS)-induced ALI in neonates and elucidate the underlying mechanisms. Phillyrin exhibited significant amelioration of lung damage in neonatal rats with LPS-induced ALI, accompanied by reductions in the total cell counts, neutrophil counts, and total protein level in bronchoalveolar lavage fluid (BALF). Notably, phillyrin substantially attenuated proinflammatory cytokine secretion and suppressed NF-κB activation in the lungs of neonatal ALI rats; however, it demonstrated inefficacy in mitigating LPS-induced cytokine secretion and NF-κB activation in vitro. Notably, phillyrin effectively inhibited β2 integrin-mediated neutrophil adhesion, migration, and chemotaxis. Moreover, phillyrin robustly suppressed β2 integrin engagement-induced actin polymerization and the Vav1/Rac1/PAK1/LIMK1/cofilin pathway. From a mechanistic standpoint, phillyrin exhibited direct interaction with β2 integrin, effectively antagonizing its function and significantly disrupting its binding affinity to intercellular adhesion molecule 1 (ICAM-1). This investigation unveils the promising therapeutic prospects of phillyrin as a novel compound against neonatal ALI.

Acute liver failure (ALF) is the result of progression from acute liver injury with high mortality, and novel treatments are needed. Yin-chen Wu-ling powder (YWP), a traditional herbal medicine in China, has been used for treating acute liver injury for thousands of years. However, the mechanism of YWP is unknown.

In vitro and in vivo studies were conducted to clarify YWP's protective effect on ALF and investigate its hepatoprotective mechanism.

We established an LPS/D-GalN-induced ALF mouse model and in vitro system to evaluate the effect of YWP. We characterized YWP's chemical composition via UHPLC-Q-Exactive Orbitrap HRMS. Enzyme-linked immunosorbent assay, hematoxylin and eosin staining, immunohistochemistry and immunofluorescence, flow cytometry, qPCR, Western blot were used to discover key mechanisms both in vitro and in vivo.

YWP alleviated liver dysfunction and liver necrosis. YWP reduced hepatocyte death and inflammatory responses. Importantly, YWP markedly inhibited neutrophil infiltration into the liver. We examined key chemokines that contribute to neutrophil recruitment. The results showed that YWP inhibited CXCL1, which is sourced from inflammation-activated hepatocytes. In addition, YWP inhibited TNF-α-induced CXCL1 transcription via the inhibition of MAPKs signaling in vitro. Furthermore, the anti-ALF effect of YWP was weakened when CXCL1/CXCR2 signaling was suppressed.

YWP alleviates inflammatory liver injury in ALF by suppressing neutrophil infiltration into the liver, potentially through inhibition of the MAPKs/CXCL1/CXCR2 axis. We suggest that YWP is a potential anti-inflammatory treatment for ALF.

This review comprehensively examines the biological and molecular mechanisms underlying wound healing, focusing on inflammation, signaling pathways, and microenvironmental imbalances. By comparing traditional and emerging therapies, we highlight innovative approaches such as gene editing, stem cell therapy, and nanotechnology, which offer new perspectives for enhancing wound treatment outcomes. This study underscores the integration of modern medicine with traditional practices, providing a robust theoretical foundation for future clinical applications.

Hematoma expansion (HE) typically portends a poor prognosis in spontaneous intracerebral hemorrhage (ICH). Several radiographic and laboratory values have been proposed as predictive markers of HE.

To perform a systematic review and meta-analysis on the association of neutrophil-to-lymphocyte ratio (NLR) and HE in ICH. A secondary outcome examined was the association of NLR and perihematomal (PHE) growth.

Three databases were searched (PubMed, EMBASE, and Cochrane) for studies evaluating the effect of NLR on HE and PHE growth. The inverse variance method was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies' estimates of the logarithm odds ratio (OR). Given heterogeneity of the studies, a random effect was applied. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The protocol was registered in PROSPERO (No. CRD42024549924).

Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis. Among those, HE was investigated in eight studies, whereas PHE growth was evaluated in three. Blood sample was obtained on admission in ten studies, and at 24 hours in one study. There was no consensus on cut-off value among the studies. NLR was found to be significantly associated with higher odds of HE (OR = 1.09, 95%CI: 1.04-1.15, I 2 = 86%, P < 0.01), and PHE growth (OR = 1.28, 95%CI: 1.19-1.38, I 2 = 0%, P < 0.01). Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.

The available literature suggests that a possible association may exist between NLR on admission and HE, and PHE growth. Future studies controlled for systemic confounders should be designed to consolidate this finding. If confirmed, NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.

Chemotherapy is an important treatment for glioblastoma (GBM) and a key component of comprehensive GBM therapy. However, the blood-brain barrier (BBB) and complex tumor microenvironment (TME) restrict the diffusion of drugs, which greatly reduces the chemotherapeutic effect on GBM. Single strategies, such as cell-based nanobots to cross the BBB or enzymatic nanobots propelled by enriched substrates in the TME for deep tumor penetration, remain inadequate to address multiple barriers and achieve precise targeting. Here, we develop a Trojan horse-inspired enzymatic nanobot-in-neutrobot system (Trojanbot) to greatly enhance targeted GBM therapy. Trojanbots traverse the BBB by leveraging positive chemotaxis in response to tumor-derived chemokine gradients, after which the released catalase-driven nanobots (CatNbot) undergo directional movement along the H2O2 gradients in TME, facilitating deep tumor penetration. This multi-stage targeting strategy improves drug delivery efficiency, providing considerable potential as a clinical approach for brain tumor treatment.

In the United States, roughly one out of every eight couples, or 7.5 million women, experience challenges related to conceiving or maintaining a pregnancy. The body's immune response is vital during pregnancy. T cells, natural killer (NK) cells, B cells, and macrophages (MQ) are immune cells in the female reproductive tract. They are in charge of maintaining tissue homeostasis and regulating the immune system's response to invasive pathogens. Failure to regulate these immune cells might result in inflammation, which reduces fertility. The immune system modulation of pregnancy loss has been studied with intralipid, intravenous immunoglobulin (IVIG), and paternal leukocyte vaccination. A concentrated antibody called intravenous immunoglobulin (IVIG) is utilized as a biological agent to treat autoimmune, viral, and inflammatory diseases and some immunodeficiencies. The main objective of this treatment is to restore a damaged immune system. IgGs, through binding to specific antigens, promote the innate immunity's cellular and humoral immune response by activating complements and binding to Fc receptors of several immune cells. Contrariwise, IVIG regulates pathogenic autoimmunity in animal models, including skin-blister diseases, nephrotoxic nephritis, and K/BxN arthritis. IVIG has, therefore, been of great interest as an immune modulator in several immune disorders. This review aims to investigate the immunological reasons of reproductive failure, focusing on the immunomodulatory effects of IVIG in its treatment.

Neutrophilic inflammation, characterized by dysregulated neutrophil activation, triggers a variety of inflammatory responses such as chemotactic infiltration, oxidative bursts, degranulation, neutrophil extracellular traps (NETs) formation, and delayed turnover. This type of inflammation is pivotal in the pathogenesis of acute respiratory distress syndrome (ARDS) and psoriasis. Despite current treatments, managing neutrophil-associated inflammatory symptoms remains a significant challenge.

This review emphasizes the role of cyclin-dependent kinases (CDKs) in neutrophil activation and inflammation. It aims to highlight the therapeutic potential of repurposing CDK inhibitors to manage neutrophilic inflammation, particularly in ARDS and psoriasis. Additionally, it discusses the necessary precautions for the clinical application of these inhibitors due to potential off-target effects and the need for dose optimization.

CDKs regulate key neutrophilic functions, including chemotactic responses, degranulation, NET formation, and apoptosis. Repurposing CDK inhibitors, originally developed for cancer treatment, shows promise in controlling neutrophilic inflammation. Clinical anticancer drugs, palbociclib and ribociclib, have demonstrated efficacy in treating neutrophilic ARDS and psoriasis by targeting off-label pathways, phosphoinositide 3-kinase (PI3K) and phosphodiesterase 4 (PDE4), respectively. While CDK inhibitors offer promising therapeutic benefits, their clinical repurposing requires careful consideration of off-target effects and dose optimization. Further exploration and clinical trials are necessary to ensure their safety and efficacy in treating inflammatory conditions.

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Activated neutrophils release Neutrophil Extracellular Traps (NETs), comprising decondensed chromatin, peroxidases, and serine proteases, which aid in host defense but are also implicated in thrombosis and resistance to thrombolysis. Recombinant DNase 1, which degrades NETs, may aid in thrombus dissolution synergistically with fibrinolytics. However, its short half-life and susceptibility to plasma proteases limit its therapeutic applicability. To address these limitations, DNase1 is encapsulated into polymeric nanoparticles (DNPs) using inverse Flash Nanoprecipitation (iFNP), a scalable nanoparticle synthesis technique. Previously only used with model proteins, the study demonstrates for the first time the feasibility of extending iFNP to the encapsulation of therapeutic proteins. Conditions that promote DNase1 solubility, preserve activity, and demonstrate release resulting in ex vivo NET degradation are detailed. Furthermore, the use of neutrophils, the source of NETs, as carriers for DNPs to enhance targeted delivery is investigated. These findings confirm that DNP-loaded neutrophils maintain key functionalities, including viability and oxidative burst, and associate with in vitro blood clots to deliver nanoparticles, and DNase1 protein. This study not only extends the feasibility of applying iFNP to encapsulate therapeutic proteins into polymeric nanoparticles, a promising alternative to lipid nanoparticles, but also contributes to the emerging literature on neutrophils as delivery vectors for nanocarriers.

Acute respiratory distress syndrome is a serious illness accounting for 10% of ICU admissions and has a high mortality of 31-45%, with a paucity of pharmacologic treatment options. Dysregulated inflammation and oxidative stress are hallmark features of acute respiratory distress syndrome. We previously showed that transgenic mice expressing a naturally occurring polymorphism of the antioxidant enzyme EC-SOD (extracellular superoxide dismutase) are protected against Staphylococcus aureus pneumonia, acute lung injury, and pulmonary neutrophilia. In this mouse strain, an R213G amino acid substitution leads to lower tissue-binding affinity and elevated alveolar and plasma EC-SOD amounts, although the redox-regulated mechanisms responsible for protection against S. aureus are not yet elucidated. Neutrophils are recruited to the areas of injury and inflammation, in part by activated platelets, which contain multiple redox-sensitive targets. Thus, we hypothesize that increased circulating EC-SOD due to the EC-SOD R213G variant protects against S. aureus pneumonia by reducing platelet activation and subsequent neutrophil recruitment to the lung. We demonstrate that, compared with wild-type mice with S. aureus pneumonia, platelet activation, formation of platelet-neutrophil aggregates, and influx of neutrophils and platelet-neutrophil aggregates into the lung are decreased in the infected R213G mice. Furthermore, pretreatment with a MnTE-2-PyP SOD mimetic protects against S. aureus-induced platelet activation, pulmonary neutrophilia, and acute lung injury. Our data highlight the redox regulation of platelet activation as a driver of S. aureus-induced acute lung injury.

Pediatric gliomas, the most frequent brain tumors in children, are characterized by heterogeneity and a unique tumor immune microenvironment. They are categorized into different subtypes, including low-grade gliomas like pilocytic astrocytomas and high-grade gliomas such as diffuse midline gliomas and diffuse intrinsic pontine gliomas, each exhibiting distinct immunological profiles. The tumor immune microenvironment in pediatric gliomas is shaped by cellular and non-cellular components, including immune cells, cytokines, and the extracellular matrix, involved in tumor progression, immune evasion, and response to therapy. While pediatric low-grade gliomas often display an immunosuppressed microenvironment, high-grade gliomas are characterized by complex immune infiltrates and intricate immunosuppressive mechanisms. The blood-brain barrier further obscures immune cell recruitment and therapeutic delivery. Despite advances in understanding adult gliomas, the immunobiology of pediatric tumors is poorly investigated, with limited data on the interactions between glioma cells and immune populations such as T and natural killer cells, as well as tumor-associated macrophages. Herein, we provide an update of the current knowledge on tumor immune microenvironment interactions in pediatric gliomas, highlighting the immunosuppressive mechanisms and emerging immunotherapeutic strategies aiming at overcoming these barriers to improve clinical outcomes for affected children.

Immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM) represent distinct subtypes of idiopathic inflammatory myopathies (IIMs). While both conditions share clinical manifestations, including muscle weakness and inflammatory infiltrates on muscle biopsy, their pathophysiological characteristics differ significantly. This study investigated the clinical utility of hematological inflammatory biomarkers in differentiating these two entities.

In this retrospective analysis, we compared complete blood count parameters among 27 patients with IMNM, 14 patients with DM, and 85 healthy controls (HC). Demographic characteristics, clinical presentations, and hematological indices including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were analyzed.

Myalgia and skin rash were observed more frequently in the DM group compared to the IMNM group. The patients with IMNM exhibited significantly higher serum creatine kinase (CK) and lactate d0.2815ehydrogenase levels. Red blood cell distribution width (RDW), monocyte counts, and MLR were elevated in the patients with IMNM compared to the HC. The patients with DM showed significantly increased neutrophil percentages, monocyte percentages, monocyte counts, NLR, MLR, and PLR, as well as decreased lymphocyte percentages and counts, compared to the HC. When directly comparing DM and IMNM, the patients with DM had lower lymphocyte percentages and counts, along with higher NLR and MLR. Receiver operating characteristic (ROC) curve analysis revealed that lymphocyte percentages and the MLR had moderate predictive value for differentiating IMNM from DM, with area under the curve (AUC) values of 0.709 and 0.7487, respectively.

RDW and the MLR in IMNM and the NLR, MLR, and PLR in DM represent accessible and cost-effective biomarkers for assessing inflammation. Lymphocyte percentages and the MLR may serve as inexpensive and readily available supplementary markers for distinguishing IMNM from DM.

Hepatitis B virus-associated decompensated cirrhosis (HBV-DC) is recognized as a critical illness with an increased risk of short-term mortality. Neutrophil-derived ratios, including neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-albumin ratio, neutrophil-to-high-density lipoprotein-cholesterol ratio, neutrophil-to-hemoglobin ratio, and neutrophil-to-platelet ratio, have emerged as potential prognostic markers in various liver diseases. The present study aimed to determine the effectiveness of these neutrophil-derived ratios for prediction of mortality in patients with HBV-DC.

We conducted a retrospective analysis of HBV-DC patients at our hospital between April 2022 and April 2024. The study endpoint was the 30-day mortality rate. These neutrophil-derived ratios were calculated from data obtained during routine laboratory tests on admission. Disease severity was assessed using the Model for End-Stage Liver Disease (MELD) score. Multivariate regression analyses and receiver operating characteristic (ROC) curve analyses were conducted.

The study investigated 160 HBV-DC patients, of whom 23 (14.4%) experienced mortality within 30 days. Non-survivors exhibited markedly higher values for neutrophil-derived ratios than survivors. All neutrophil-derived ratios were associated with mortality in univariate analyses, but only NLR and MELD score remained as independent predictors of mortality in multivariate analyses. In the ROC analyses, NLR showed a similar prognostic value to MELD score. Moreover, both NLR and MELD score had high specificity for prediction of mortality in HBV-DC patients.

Among neutrophil-derived ratios, NLR stands out as a simple and reliable predictor of mortality in HBV-DC patients.

Gastric cancer (GC), a common and deadly malignancy worldwide, is a serious burden on society and individuals. However, available diagnostic biomarkers for GC are very limited. The current study aimed to identify potential diagnostic biomarkers for GC and analyze the activity of infiltrating immune cells in this pathology.

Microarray data for GC were acquired from the Gene Expression Omnibus (GEO) database. The limma package was utilized to normalize these data, thus identifying differentially expressed genes (DEGs). For normalized data of samples, we established a weighted gene co-expression network (WGCNA) to reveal key genes in the significant module. Afterward, we obtained overlapping genes by intersecting the DEGs and the key genes from the WGCNA module. Next, after applying the three algorithms (LASSO, RandomForest, and SVM-RFE) to analyze these overlapping genes and take the intersection, we established a GC diagnosis. The diagnostic significances of these identified genes were evaluated with receiver operating characteristic (ROC) curves and validated in the external dataset. Furthermore, ssGSEA and CIBERSORT were employed for evaluating the infiltrating immune cells and the association of the immune cells and diagnostic biomarkers.

Herein, we identified 49 overlapping genes, and the results of enrichment analysis demonstrated that these genes may be involved in the signaling transduction-related process. Finally, BANF1, DUSP14, and VMP1 were regarded as key biomarkers in GC patients based on the overlapping genes that we found, and these three biomarkers demonstrated great diagnostic significance. Additionally, the hub biomarkers had different levels of association with macrophages, neutrophils, memory B cells, and plasma cells.

BANF1, DUSP14, and VMP1 are promising diagnostic biomarkers for GC, and infiltrating immune cells may dramatically affect gastric carcinogenesis and progression.

The immune response exhibits strong circadian rhythmicity, with enhanced bacterial clearance often synchronized with an organism's active phase. Despite providing the bulk of cellular antibacterial defense, the neutrophil clockwork is poorly understood. Here, we used larval zebrafish to explore the role of clock genes in neutrophils during infection. Per2 was required in neutrophils for reactive oxygen species (ROS) production and bacterial killing by enhancing infection-responsive expression of high-mobility group box 1a (hmgb1a). The Cry binding domain of Per2 was required for regulation of neutrophil bactericidal activity, and neutrophils lacking Cry1a had elevated bactericidal activity and infection-responsive hmgb1a expression. A conserved cis-regulatory element with BMAL1 and nuclear factor κB binding motifs gated infection-responsive hmgb1a expression to the light phase. Mutagenesis of the BMAL1 motif in neutrophils blunted the priming effect of light on bactericidal activity and hmgb1a expression. These findings identify a light-responsive cell-intrinsic timer that controls time-of-day variations in antibacterial activity.

Sarcopenia is defined by age-related reductions in muscle mass, strength, and physiological function, and it is especially prevalent among individuals with autoimmune diseases. Autoimmune disorders, characterized by immune dysregulation, cause systemic inflammation and damage to multiple tissues through unregulated immune activity. Research indicates that autoimmune diseases negatively impact skeletal muscle functions and may worsen the progression of sarcopenia. This viewpoint comprehensively discusses the pathogenesis and potential mechanism of sarcopenia in 3 autoimmune diseases: inflammatory bowel disease, rheumatoid arthritis, and type 1 diabetes mellitus. Mechanistically, chronic immune microenvironment alterations induce compartment-specific redistribution of leukocyte subsets and cytokine networks. These perturbations disrupt critical signaling pathways governing muscle protein synthesis, satellite cell activation, and mitochondrial bioenergetics, leading to impaired regeneration and accelerated sarcopenia progression. By delineating shared and distinct pathomechanisms across these models, this analysis reframes our understanding of immune-mediated muscle wasting. Beyond mechanistic insights, it establishes a translational framework for targeted therapies and highlights emerging research directions bridging immunology and age-related musculoskeletal decline.

Ischemia-reperfusion injury (IRI) during kidney transplantation is linked to oxidative stress induced by excessive reactive oxygen species (ROS), which causes the injury of transplanted kidney, leading to further intensified organ shortages. Protein-based antioxidants have been developed for ROS scavenging via cascade biocatalyst. The in situ growth of metal nanozymes on proteins effectively decreases the steric hindrance between active sites, improving the efficiency of cascade biocatalysts. However, the poor stability of protein during the process of preparation and intracellular delivery leads to low therapeutic effects. In this study, three different functional polymers are conjugated to SOD for the formation of micelles. Surprisingly, it is found that the conjugated ultra-acid sensitive polymer efficiently preserves the enzymatic activity of SOD, due to great endo/lysosomal escape capacity. Subsequently, SOD micelles (SOE) are used as a template to prepare SOE-Pt0 (SOEP) through in situ growth of Pt0 with vicinal enzymatic active sites. The preparation process minimally impacts on the activity of SOD, owing to improved stability. The system exhibits effective cascade ROS scavenging, significantly reducing kidney damage and inflammation caused by IRI. The research offers a novel approach for addressing IRI challenges in organ transplantation and provides a promising strategy to mitigate organ shortages.

Type I interferon (IFN-I), a pivotal component of the host's innate antiviral immune system, can induce the formation of neutrophil extracellular traps (NETs) and facilitate inflammatory responses. Baicalin exhibits a range of pharmacological activities, including anti-inflammatory and immunomodulatory effects. It has been reported that neutrophil glycolysis plays a pivotal role in the formation of NETs and the regulation of inflammatory response in immune modulation, regulated by IFN-I. However, it remains unclear whether baicalin regulates IFN-I-induced NETs formation through glycolysis. In this study, we induced the formation of NETs in vitro using IFN-I and observed that baicalin significantly reduced the formation of IFN-I-induced NETs. Furthermore, baicalin inhibited the production of pro-inflammatory cytokines, specifically interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), as well as the generation of reactive oxygen species (ROS) and chemotactic responses. Our findings further indicated that baicalin could inhibit both lactic acid and ATP levels in IFN-I-induced neutrophils, as well as the expression of glycolytic-related proteins, including HK2, HK3, PKM2, and LDHA. Moreover, following the administration of glycolytic agonists insulin, it was observed that heightened glycolytic activity significantly augmented NETs formation and the release of inflammatory cytokines, potentially regulated by PKC/Raf/MEK/ERK and PI3K/AKT signaling pathways. In conclusion, our findings indicated that baicalin may exert inhibitory effects on IFN-I-induced NETs formation and inflammatory cytokine production by modulating glycolysis, thereby providing further evidence for the potential clinical application of baicalin in the treatment of IFN-I-related inflammatory diseases.

The sympathetic splanchnic nerve is a major player in immunoregulation, but its specific roles during infection have yet to be elucidated. Here, we evaluated how bilateral ablation of the greater splanchnic nerve (SplancX) impacts bacterial burden and immune function in a rat model of E. coli-induced septic peritonitis. SplancX had a major effect on bacterial burden within 24 h, reducing it to 4 % in the peritoneum and to 8 % in the spleen of what was found in the sham-operated controls. Such a major effect was not explained by gross changes in the infiltration of these sites with innate immune cells (neutrophils and macrophages), as assessed by flow cytometry. Single-cell RNA sequencing was then employed to evaluate the cellular activation programs of leukocyte subsets. Of the nine cellular clusters identified in the peritoneum of the infected rats, three of them had a transcriptional signature of activated neutrophils and two of them corresponded to quiescent neutrophils with an immunosuppressive signature. SplancX shifted the balance between these neutrophil subsets in a way consistent with heightened immunity, i.e., the activated neutrophils were augmented whereas the quiescent neutrophils were reduced in the SplancX group. The remainder of the clusters consisted of macrophages and erythrocytes, none of which changed in a way that could account for the observed effects on bacterial clearance. Confirming that SplancX resulted in heightened neutrophil activation, protein markers of neutrophil degranulation and NETosis were found to be elevated in the peritoneal lavage of the SplancX group. Taken together, the data show that the splanchnic nerve exerts a major effect on bacterial clearance in the acute phase of infection, presumably owing to selective changes in the balance between microbicidal and quiescent subsets of neutrophils.

Migrasomes are newly discovered extracellular organelles released by migrating cells, such as immune cells, tumor cells, and other special functional cells like podocytes and embryonic cells. They contain a diverse array of constituents, including proteins, lipids, and RNA which can be released to the designated location to activate surrounding cells, thereby facilitating intercellular communication and signal transduction. Since then, our understanding of the mechanism and function of the migrasomes has expanded exponentially, with recent evidence indicating they are involved in various physiological and pathological processes, particularly in immune regulation. Furthermore, methods and techniques for extracting, detecting, and characterizing migrasomes are constantly advancing. Herein, we summarize the current understanding of migrasomes and their key roles in modulating immune responses, as well as the prospective challenges surrounding their clinical application, aiming to provide novel insights into the emerging organelles.

Chrysin (CHR) is the principal active compound in honey, propolis and plants. Its pharmacological effects include anti-inflammatory, antiallergic, and antioxidant capabilities. However, its poor solubility and bioavailability constitute a limitation. In this study, Poly-lactic-co-glycolic acid (PLGA) was used as a nanocarrier to enhance the stability, bioavailability, and effectiveness of CHR to protect mice from indirect acute lung injury (ALI) caused by lipopolysaccharide (LPS). CHR-loaded PLGA nanoparticle (CHR-NP) was prepared and characterized using techniques such as FTIR, zeta potential analysis, DLS, in vitro drug release assessment, encapsulation efficiency measurement, and TEM. Prior to the intraperitoneal injection of LPS (10mg/kg), C57BL/6 mice were orally administered CHR (50mg/kg), PLGA (50mg/kg), CHR-NP (50mg/kg), and dexamethasone (Dexa) (5mg/kg) for a duration of six days. Following 24hours of LPS or normal saline (control) injection, the mice were anesthetized. CHR-NP increased catalase, glutathione, and glutathione peroxidase while decreasing malondialdehyde, myeloperoxidase, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-12, and interferon (IFN)-γ. Moreover, treatment with CHR-NP augmented the gene and protein expression of the Keap1/Nrf2/ARE signaling pathway utilizing quantitative real-time PCR (RT-PCR), western blotting, and immunohistochemistry. Additionally, CHR-NP reduced histological alterations, pulmonary edema, damage, and iron deposition. Our findings indicate that CHR-NP significantly mitigated indirect ALI, primarily through the suppression of inflammation, oxidative stress, and ferroptosis via the activation of the Keap1/Nrf2/ARE signaling pathways.

Neutrophil extracellular traps (NETs) play a pivotal role in immunity and autoinflammatory disease, leading us to hypothesize that NETs are crucial in Guillain-Barre Syndrome (GBS) after SARS-CoV-2 infection.

By collecting six Gene Expression Omnibus (GEO) datasets from the GEO database and dividing them into discovery and validation sets, we screened differentially expressed genes (DEGs) within the discovery set, with further analyses using functional enrichment analysis. Using single-sample gene set enrichment analysis (ssGSEA), we assessed immune cell infiltration in both coronavirus disease 2019 (COVID-19) and GBS datasets. NETs-related genes (NETRGs) were identified through a protein-protein interaction (PPI) network and NETs gene datasets. Finally, candidate drugs were screened using Connectivity Map.

In this study, a total of 3254 DEGs were identified from the COVID-19 dataset, and 692 DEGs were obtained from the GBS dataset. Among these, 145 co-expressed DEGs were obtained. Bioinformatics functional analysis indicated that co-expressed DEGs were predominantly gathered in immune-related and inflammatory response pathways. Employing various algorithms, we identified MMP9, CAMP, and CASP1 as NETRGs, demonstrating good discriminatory capacity in COVID-19 and GBS. Notably, neutrophils and macrophages were identified as co-upregulated differential immune infiltrating cells significantly associated with both COVID-19 and GBS. Moreover, we identified 10 candidate drugs for patients with post-COVID-19 GBS.

In conclusion, MMP9, CASP1, and CAMP were identified as promising biomarkers and potential targets for therapy of post-COVID-19 GBS.

The increasing prevalence of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii (XDR-Ab) poses a critical challenge in treating hospital-acquired pulmonary infections. In this study, we developed a biomimetic neutrophil membrane-coated nanoparticle system, NM@PCN-TIG, for the targeted delivery of tigecycline (TIG). The system utilizes the porphyrin-based metal-organic framework (MOF) PCN-224 as the core of the nanoparticle, encapsulating TIG and coated with a neutrophil membrane (NM) to enhance immune evasion and targeting of infection sites. Its loading efficiency, controlled release properties, cytotoxicity, and bactericidal activity under ultrasound mediation were systematically evaluated in vitro and in vivo. Our results demonstrated that NM@PCN-TIG significantly enhanced the bactericidal efficacy of TIG, increased reactive oxygen species (ROS) production, and promoted macrophage polarization toward an anti-inflammatory phenotype. This innovative biomimetic TIG nanosystem shows great potential as a platform for addressing XDR-Ab-induced pneumonia.

Wound healing is a complex biological process and remains a significant challenge due to the lack of effective therapeutic drugs. Cayratia japonica (CJG), a traditional folk medicine, has been widely used for its anti-inflammatory and efficacy in treating traumatic injuries.

This study aimed to investigate the wound-healing effects of CJG and elucidate its underlying mechanism.

First, the phytochemical composition of CJG was identified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and its potential wound-healing mechanisms were predicated via network pharmacology. Next, in vivo experiments were conducted by dividing subjects into control, CJG (1.5-6 mg/cm2), and bFGF (150 IU/cm2) groups to assess its therapeutic efficacy. Finally, the mechanism of CJG and its key bioactive component, luteolin-7-O-glucoside (LUT-7G), were explained through polymerase chain reaction (PCR), Western blotting, histopathology, immunofluorescence, plasmid transfection, colony formation unit assays, and cellular thermal shift assay (CETSA).

LC-MS/MS identified 15 major constituents of CJG and 102 potential wound healing-related targets. Network pharmacology analysis revealed key enriched pathways, including AMPK, TNF, and metabolic pathways. In vivo, CJG significantly accelerated wound-healing by inhibiting inflammatory responses, promoting angiogenesis, and modulating collagen deposition. In vitro, LUT-7G treatment markedly enhanced the proliferation and migration of HaCaT and HSF cells. Mechanistically, LUT-7G exerted its wound-healing effects by activating the AMPK/CTHRC1/TGF-β1 signaling pathway in HaCaT cells. In conclusion, CJG significantly promotes wound healing by regulating AMPK signaling pathways, indicating its promising clinical application prospects.

Alcoholic beverages play a significant role in social engagement worldwide. Excessive alcohol causes a variety of health complications. Alcohol-induced liver disease (ALD) is responsible for the bulk of linked fatalities. The activation of immune mechanisms has a crucial role in developing ALD. No effective medication promotes liver function, shields the liver from harm, or aids in hepatic cell regeneration. Alcohol withdrawal is one of the most beneficial therapies for ALD patients, which improves the patient's chances of survival. There is a crucial demand for safe and reasonably priced approaches to treating it. Exploring naturally derived phytochemicals has been a fascinating path, and it has drawn attention in recent years to modulators of inflammatory pathways for the prevention and management of ALD. In this review, we have discussed the roles of various immune mechanisms in ALD, highlighting the importance of intestinal barrier integrity and gut microbiota, as well as the roles of immune cells and hepatic inflammation, and other pathways, including cGAS-STING, NLRP3, MAPK, JAK-STAT, and NF-kB. Further, this review also outlines the possible role of phytochemicals in targeting these inflammatory pathways to safeguard the liver from alcohol-induced injury. We highlighted that targeting immunological mechanisms using phytochemicals or herbal medicine may find a place to counteract ALD. Preclinical in vitro and in vivo investigations have shown promising results; nonetheless, more extensive work is required to properly understand these compounds' mechanisms of action. Clinical investigations are very crucial in transferring laboratory knowledge into effective patient therapy.

Chronic obstructive pulmonary disease (COPD) is an intractable disease with thick mucus layer in bronchi and alveoli, frequently accompanied by bacterial infection. Anti-bacterial drugs with mucus penetrating are urgently needed for efficient COPD treatment. Here, a neutrophil-mimicking nanovehicle was developed by coating neutrophil membrane onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing antibiotics levofloxacin (LVX). Neutrophil membrane coated nanoparticles (LVX@PLGA@Mem) reserved most of the membrane proteins and related membrane functions of neutrophil, exhibiting pro-inflammatory cytokines neutralization, inflammation inhibition, successfully delivering LVX through the mucus layer and achieving satisfactory anti-infection effects. Thus, LVX@PLGA@Mem after inhalation could remarkably reduce inflammation and infection in the lung with COPD. Therefore, neutrophil mimicking nanovehicles may be a feasible and desirable drug carrier for lung-related disease treatment in further clinic.

Nanodrug delivery systems (NDDS) have demonstrated broad application prospects in disease treatment, prevention, and diagnosis due to several advantages, including functionalization capability, high drug-loading capacity, drug stability protection, and the enhanced permeability and retention (EPR) effect. However, their clinical translation still faces multiple challenges, including rapid clearance by the reticuloendothelial system (RES), poor targeting specificity, and insufficient efficiency in crossing biological barriers. To address these limitations, researchers have developed the biological carrier-mediated nanomedicine hitchhiking strategy (BCM-NHS), which leverages circulating cells, proteins, or bacteria as natural "mobile carriers" to enhance drug delivery. This approach enables nanocarriers to inherit the intrinsic biological properties, endowing them with immune evasion, prolonged circulation, dynamic targeting, biocompatibility, biodegradability, and naturally optimized biological interfaces. Here, a systematic overview of the BCM-NHS is provided. First, the review delves into the methods of nanoparticles (NPs) binding and immobilization, encompassing both the surface-attachment-mediated "backpack" strategy and the encapsulation-based "Trojan horse" strategy. Second, the classification of biological carriers, including both cell-based and non-cell-based carriers, is elucidated. Third, the physical properties and release mechanisms of these nanomaterials are thoroughly described. Finally, the latest applications of BCM-NHS in therapeutic and diagnostic contexts across various disease models including tumor, ischemic stroke, and pneumonia are highlighted.

Acute pancreatitis (AP) is a sterile inflammation, and 10-20% of cases can progress to severe acute pancreatitis (SAP), which seriously threatens human life and health. Neutrophils and their extracellular traps (NETs) play an important role in the progression of AP. However, the immunodynamic factors between the excessive infiltration of neutrophils during the occurrence of AP have not been fully elucidated.

Adult male C57BL/6 J mice were selected. An AP model was induced by cerulein, and a control group was set up. Single-cell sequencing technology was used to reveal the cell atlas of AP pancreatitis tissue. In vivo, the model mice were treated with anti-Ly6G antibody, DNase I, SC75741, PX-478, and SRT3109 respectively. In vitro, human pancreatic stellate cells were treated with hypoxia, H2O2, NAC, and JSH-2, and co-cultured with neutrophils in Transwell chambers. The severity of inflammation was evaluated, and the molecular mechanism by which fibroblasts exacerbate AP was revealed through techniques such as cell colony formation assay, cell migration assay, cell transfection, immunofluorescence, flow cytometry, Western blot, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and co-immunoprecipitation (co-IP).

The study showed that the elimination of neutrophils and NETs could significantly improve AP. Single-cell RNA sequencing (scRNA-seq) indicated that both neutrophils and fibroblasts in pancreatic tissue exhibited heterogeneity during AP. Among them, neutrophils highly expressed CXCR2, and fibroblasts highly expressed CXCL1. Further experimental results demonstrated that the infiltration of neutrophils in the early stage of AP was related to the activation of fibroblasts. The activation of fibroblasts depended on the nuclear factor kappa B (NF-κB) signaling pathway induced by hypoxia. NF-κB enhanced the activation of pancreatic stellate cells (PSCs) and the secretion of CXCL1 by directly promoting the transcription of HIF-1α and indirectly inhibiting PHD2, resulting in the accumulation of HIF-1α protein. The NF-κB-HIF-1α signal promoted the secretion of CXCL1 by fibroblasts through glycolysis and induced the infiltration of neutrophils. Finally, blocking the NF-κB-HIF-1α-CXCL1 signaling axis in vivo reduced the infiltration of neutrophils and improved AP.

This study, for the first time, demonstrated that activation of fibroblasts is one of the immunological driving factors for neutrophil infiltration and elucidated that glycolysis driven by the NF-κB-HIF-1α pathway is the intrinsic molecular mechanism by which fibroblasts secrete CXCL1 to chemotactically attract neutrophils. This finding provides a highly promising target for the treatment of AP.

Neutrophils are the most abundant leukocytes in the circulation and critical players in host defense and inflammation. They respond rapidly to numerous biological, chemical, and physical stimuli, making it challenging to characterize their steady-state phenotypes, activation states, and subsets in an unbiased and precise manner. To address this problem, we designed a 33-color spectral flow cytometry panel for the deep profiling of unprocessed neutrophils in human blood. This panel allows the profiling of neutrophil phenotypes related to activation, immune modulation, granule release, ontogeny, phagocytic capacity, and migration, in addition to monitoring all major human leukocyte populations. We validated the panel using whole blood stimulations that induce distinct phenotypic shifts in the neutrophil population. This optimized spectral flow cytometry panel allows comprehensive immune profiling of the functional heterogeneity of human blood neutrophils and is suitable for longitudinal or exploratory analysis of neutrophil dynamics and activation states in clinical cohorts.

Neutrophil count is associated with atherosclerotic plaque formation and cardiovascular diseases (CVD). As previous studies have been predominantly conducted in Caucasians, the significance of neutrophil count as a clinical factor in CVD in other ethnicities remain unclear.

A total of 2,955 participants from the Chin-Shan Community Cardiovascular Study(CCCC), who had no established CVD diagnosis and missing data, were enrolled in this study and followed from 1990-1991-2013. We use Cox regression models to calculate hazard ratio (HR) and 95% confidence interval (CI) to evaluate the association between neutrophil count and CVD risk. Subgroup analyses were performed based on sex and age, while sensitivity analyses were conducted by excluding participants with extreme values.

Over a median follow-up period of 22 years, 400 cases of new-onset CVD were recorded. Cox proportional hazards regression analysis revealed that a higher neutrophil count was independently associated with CVD incidence in Taiwanese adults, with an HR of 1.42 (95% CI 1.03-1.94) after adjusting for multiple covariates. This association remained consistent in both the subgroup and sensitivity analyses.

Our study demonstrated that, in the Taiwanese population, a higher neutrophil count was associated with a higher incidence of CVD over an average 22-year follow-up in individuals without preexisting CVD.

Flap necrosis post-operation disturbs surgeons during plastic and reconstructive surgery. This is caused by hypoperfusion and subsequent ischemia-reperfusion injury, where restricted blood flow followed by restored circulation paradoxically exacerbates tissue damage. Mesenchymal stem cells, which show multidirectional differentiation, provide hematopoietic support and are involved in immune regulation and anti-fibrosis, have inspired research on improving the blood supply of flaps.

Primary human umbilical cord mesenchymal stem cells (HuMSCs), were obtained and subcultured for expansion. The cells of the third generation were incubated in a gelatin sponge. Thirty Kunming mice were randomly divided into three groups, and saline, HuMSCs, and HuMSCs-CM were injected preoperatively into the skin of the back. The vessel density was assessed on the tenth day. Forty-eight Kunming mice were divided into two groups. Group A was subdivided into the saline group, HuMSCs, and HuMSCs-CM groups and pretreated as described above. In Group B, the intervention was changed from injection to subcutaneous embedding. Random flaps were made on the back in both groups on the tenth day after pretreatment. The survival rate of the flap was calculated on the seventh day.

HuMSCs-CM significantly increased the microvessel density on the tenth day after pretreatment. The flap survival rate was higher in the cell and CM groups, rising from approximately 13% to 60% in Group A, and to about 75% in Group B. Moreover, subcutaneous embedding of cell-carrying gelatin sponges improved flap survival compared to other interventions.

Improved cell incubation conditions can enhance its utility. The application of HuMSCs and their conditioned medium promoted the survival of the flap by inducing neovasculogenesis.

Alveolar echinococcosis (AE) is caused by the chronic infection of E. multilocularis, whose tumor-like growth can lead to high fatality if improperly treated. The early diagnosis of infection and the treatment of advanced AE remain challenging. Herein, bulk RNA-seq, scRNA-seq, and spatial transcriptomics technologies are integrated, to reveal the host immune response mechanism against E. multilocularis both spatially and chronologically, collecting mouse liver samples at multiple timepoints up to 15 months post infection. These results unveil an unprecedented high-resolution spatial atlas of the E. multilocularis infection foci and the functional roles of neutrophils, Spp1+ macrophages, and fibroblasts during disease progression. The heterogeneity of neutrophil and macrophage subpopulations are critical in both parasite-killing and the occurrence of immunosuppression during AE progression. These findings indicate the transition of parasite control strategy from "active killing" to "negative segregation" by the host, providing instructive insights into the treatment strategy for echinococcosis.