Annexin A1 in Alzheimer's disease: A new therapeutic strategy focusing on neuroinflammation.

Anti-Annexin A5 antibodies and Annexin A5 resistance in antiphospholipid syndrome: A systematic review and meta-analysis.

Dental resin monomers are widely used in restorative dentistry, yet their potential effects on kidney-related cell types remain poorly understood. This study investigated the effects of bisphenol A-glycidyl methacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) on protein expression and cytoskeletal regulatory pathways in human mesangial cells. A proteomic analysis demonstrated differential expression of multiple members of the annexin A protein family in treated human mesangial cells compared with vehicle-treated controls. These findings were validated by western blotting and densitometric analysis, which revealed reduced expression of annexin A proteins, including annexin A2 and annexin A5, following exposure to TEGDMA. To further explore the functional relevance of annexin A2, transient knockdown using small interfering RNA was performed. Reduction of annexin A2 expression using siRNA resulted in decreased levels of alpha-smooth muscle actin and non-muscle myosin proteins compared with cells transfected with non-targeting control RNA. Collectively, these results indicate that commonly used dental resin monomers may influence protein expression and cytoskeletal-associated pathways in human mesangial cells through alterations in annexin A protein expression. The findings highlight a previously underexplored cellular response to dental methacrylates and suggest potential implications for renal cell biology under controlled in vitro conditions.

The cGAS-STING axis is essential for host resistance to DNA virus infections by regulating type I interferon (IFN) production. This study is significant because it identifies Annexin A2 (ANXA2) as a previously unrecognized and potent negative regulator of the host antiviral response against DNA viruses like herpes simplex virus-1. The findings demonstrate that ANXA2 suppresses type I interferon production through a dual mechanism: by inhibiting the critical transport of STING to the Golgi apparatus and by disrupting the kinase activity of TBK1/IKKε required for IRF3 activation. This role is independent of its known partner S100A10, revealing a novel function for ANXA2. The validation in knockout mice, which showed enhanced IFN production and restricted viral replication, confirms its physiological importance in vivo. By pinpointing ANXA2 as a key inhibitor of the cGAS-STING pathway, this research not only advances our understanding of immune regulation but also identifies ANXA2 as a potential therapeutic target for modulating antiviral defenses.

Severe COVID-19 is marked by a dysregulated inflammatory response, known as a cytokine storm, resulting in acute respiratory distress syndrome (ARDS) and multiple organ failure. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated potential as immunomodulatory agents. This work investigates the possibility of MSC-Exos to mitigate excessive inflammation in COVID-19 by targeting the mitogen-activated protein kinase (MAPK) signalling pathway. We integrated molecular docking analysis between TGF-β and Annexin A1 as exosomal proteins and key component proteins of the MAPK pathway (p38, ERK1/2, JNK1). The in-silico results were then validated in vivo using a Syrian hamster model of SARS-CoV-2 infection. Quantitative PCR (qPCR), western blotting, and histological examination were employed to evaluate the effects of MSC-Exos therapy on MAPK pathway activation, cytokine production, and lung tissue pathology. The in-silico study revealed extensive hydrogen bonding and hydrophobic interactions at the protein-protein interfaces between exosomal proteins and MAPK components. These interactions suggest that exosomal proteins may modulate MAPK signaling pathways. In vivo, MSC-Exos administration led to marked downregulation of pivotal genes in the MAPK signaling pathway (MEKK1, MEKK2, MEKK3), diminished phosphorylation of JNK1, p38, and ERK1/2, and lowered production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Histopathological examination demonstrated ameliorated lung tissue structure, characterized by diminished alveolar wall thickness and decreased immune cell infiltration. MSC-Exos elicit immunomodulatory effects in SARS-CoV-2-Infected hamsters, partially by directly targeting and blocking the MAPK signaling pathway. These findings offer a compelling justification for the clinical assessment of MSC-Exos as a therapeutic approach to alleviate the cytokine storm and enhance outcomes in severe COVID-19 by targeting the ACE2-Independent pathway.

To study the effects of different concentrations of glutathione peroxidase (GSH-Px) on sperm motility and viability, structural integrity, antioxidant capacity and metabolic enzyme activity after frozen semen of sheep, and to evaluate the expression of differential proteins. Semen samples were collected from six Dorper rams, pooled, and subsequently divided into four groups. Glutathione peroxidase was added to the cryoprotectant solution at concentrations of 0, 0.8, 1.6, and 3.2 units per liter, respectively. Following thawing, sperm motility, viability, and kinematic parameters were assessed, along with acrosomal and plasma membrane integrity, DNA integrity, mitochondrial activity, antioxidant status, metabolic enzyme activity, and proteomic profiles. Adding 1.6 U/L GSH-Px to the freezing extender significantly enhanced the motility and viability of sperm after freeze-thaw, as well as the integrity of the acrosome, plasma membrane and DNA. The activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) were significantly increased. The oxidative stress marker malondialdehyde (MDA) was significantly reduced, and the activities of metabolic enzymes including lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also decreased. Proteomic analysis identified 150 differentially expressed proteins (DEPs). Western blotting verification confirmed the upregulation of G1 to S Phase Transition 1 (GSPT1), ribosomal protein L11 (RPL11), as well as the downregulation of annexin A2 (ANXA2) expression. Supplementation of the cryopreservation extender with 1.6 U/L glutathione peroxidase (GSH-Px) significantly improves post-thaw ovine sperm quality, as evidenced by enhanced structural integrity, elevated total antioxidant capacity, and attenuated oxidative stress-induced damage.

Alzheimer's disease (AD), a progressive neurodegenerative disorder with a rising global prevalence, is pathologically characterised by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). These lesions lead to synaptic damage, neuronal loss, and cognitive impairment. Despite the recent approval of immunotherapies for AD treatment, their limited efficacy highlights the urgent need for exploring novel disease mechanisms and developing targeted therapeutic strategies. Annexin A2 (ANXA2), a calcium-dependent phospholipid-binding protein, participates in diverse physiological processes (e.g. membrane organisation, cytoskeleton linkage) and contributes to the pathogenesis of diseases such as cancer and Parkinson's disease. Emerging evidence indicates that ANXA2 interacts with AD-related pathological components (Aβ, tau) and regulates AD-associated inflammatory pathways, suggesting its potential role in AD. However, current evidence regarding ANXA2 in AD remains limited, and the molecular mechanisms underlying its contribution to AD pathogenesis remain unclear. This review comprehensively summarises the current knowledge on ANXA2's cellular and physiological functions in the central nervous system (CNS), as well as its involvement in AD pathology, aiming to provide guidance for research into ANXA2's therapeutic potential for AD prevention and treatment.

Annexin A5 ameliorates immune-mediated liver injury by regulating ferritinophagy-ferroptosis in M2 macrophages via the NRF2/ERK pathway.

Extracellular vesicles in type 2 diabetes exhibit elevated miR-155 cargo and Annexin A1 concentration.

Annexin A1 enhances liver repair after acetaminophen-induced liver injury by regulating neutrophils function.

Annexin A2 orchestrates CSFV entry route selection via the annexin A2/S100A10 heterotetrameric complex.

Streptococcus pneumoniae is a gram-positive bacterium, colonizer of the human nasopharynx capable of causing severe invasive disease. Colonization of the nasopharynx is a prerequisite for the development of invasive disease and depends upon surface-bound bacterial proteins interacting with host cell receptors. Pneumococcal surface adhesin A (PsaA) is a highly conserved lipoprotein involved in the attachment to host airway cells via the host receptor Annexin A2 (ANXA2). However, the specific structural domains of PsaA responsible for ANXA2 recognition and binding remain unknown. Here, we employed a structure-based peptide approach to map the ANXA2-binding domain of PsaA. Five recombinant PsaA peptides were designed and generated based on the crystal structure of PsaA. Far-western blot analysis using ANXA2-overexpressing HEK293T/17 cell lysates revealed that the interaction with ANXA2 was specific to the C-terminal subdomain of PsaA. Cell-binding assays and flow cytometry further confirmed the interaction between the C-terminal subdomain of PsaA and cell surface-expressed ANXA2. Furthermore, polyclonal antibodies against the C-terminal subdomain significantly inhibited the binding of full-length PsaA to ANXA2-overexpressing cells, whereas antibodies against other subdomains did not. Consistently, polyclonal antibodies against the C-terminus of PsaA reduced the binding of S. pneumoniae to A549 lung epithelial cells to a greater extent than other antibodies. Together, these findings establish that the C-terminus of PsaA is crucial for ANXA2 receptor recognition. Targeting this specific subdomain may be a promising strategy for developing next-generation protein-based pneumococcal vaccines that aim at blocking bacterial adherence.IMPORTANCEStreptococcus pneumoniae is a leading cause of millions of deaths worldwide each year due to its ability to transition from an asymptomatic colonizer to an invasive pathogen. Current pneumococcal conjugate and polysaccharide vaccines protect against pneumococcal disease, but overall colonization rates have remained stable. Since pneumococcus is an opportunistic pathogen, decreasing overall colonization rates is essential for preventing progression to disease. The significance of our research lies in mapping functional epitopes within key pneumococcal adhesins that play a critical role in bacterial adherence. Defining these adhesion epitopes is essential for the rational design of next-generation protein-based vaccines capable of blocking colonization and ultimately reducing the global burden of invasive pneumococcal diseases.

Aqueous extract of Solanum nigrum L. restrains colorectal cancer progression by blocking cancer-associated fibroblast-induced STAT3-Annexin A2 signaling.

Endometriosis (EMs) features ectopic implantation of endometrial stromal cells (EESCs) and strong anoikis resistance, yet how inflammatory signals reprogram mitochondrial function remains unclear. Here, neutrophil extracellular traps (NETs), particularly their DNA scaffold (NET-DNA), are identified as enriched in early lesions and associated with enhanced mitophagy and EESCs survival. In primary human EESCs, NET-DNA suppresses anoikis, increases mitochondrial membrane potential, decreases reactive oxygen species, and enhances ER-mitochondria contacts. NET-DNA directly binds Annexin A2 (ANXA2), promotes its redistribution from the plasma membrane to the cytoplasm, and independently upregulates the ER-resident transmembrane protein TMEM215. TMEM215 facilitates formation of a Ca2+-dependent ANXA2-TMEM215 complex, enhancing ER-mitochondria contacts and PINK1/Parkin-mediated mitophagy. Silencing ANXA2 or TMEM215 disrupts mitophagy, impairs mitochondrial Ca2+ handling, reduces ER-mitochondria contacts, and restores anoikis sensitivity. Proteomic analysis identifies Binding Immunoglobulin Protein (BiP/GRP78) as a TMEM215-interacting partner, and NET-DNA promotes assembly of a TMEM215-ANXA2-BiP complex that reinforces mitochondrial quality control. In mouse EMs models, knockdown of TMEM215 or ANXA2 reduces lesion growth and partially reverses LPS-associated progression. These findings reveal a mechanism linking inflammation to mitochondrial reprogramming in EMs and suggest a potential therapeutic target.

An in-depth synthetic wrap on the immune-hemostatic axis in human disease.

Annexin A2 (ANXA2) is a calcium-dependent protein with high affinity for phospholipids, and its multifunctional nature has drawn increasing attention in the onset and progression of various disorders of the female reproductive system (FRS). Beyond its canonical roles in endocytosis, cytoskeletal dynamics, angiogenesis, and extracellular matrix (ECM) remodeling, ANXA2 signaling integrates phosphorylation events, interactions with S100A10, and fibrinolytic activity to shape reproductive biology. Emerging evidence demonstrates that aberrant ANXA2 expression is implicated in gynecological cancers, endometriosis, adenomyosis, infertility, and pregnancy-related complications, where it modulates processes such as epithelial-mesenchymal transition, trophoblast invasion, vascular integrity, and immune homeostasis. Elevated ANXA2 levels have been correlated with tumor aggressiveness, recurrence risk, chemoresistance, and poor prognosis, while circulating ANXA2 and exosome-derived ANXA2 show promise as minimally invasive biomarkers for benign reproductive system disorders. Despite these advances, the precise molecular mechanisms and context-specific functions of ANXA2 remain incompletely understood, and significant gaps persist regarding its clinical translation. This review synthesizes current knowledge of ANXA2 signaling in female reproductive diseases, highlights its potential diagnostic and therapeutic value, and identifies key challenges and research priorities. A deeper understanding of ANXA2 biology may not only refine disease stratification and prognosis but also open new avenues for targeted interventions, positioning ANXA2 as a promising node for precision medicine in reproductive health.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies with limited treatment options. Lenvatinib is a first-line drug for advanced HCC. However, its effect on patient survival is limited and patients ultimately develop disease progression due to drug resistance. In this study, we established a lenvatinib-resistant orthotopic xenograft model and found a significant upregulation of ANXA3. Further researches revealed that ANXA3 facilitated lenvatinib resistance in vitro and in vivo. Mechanistically, ANXA3 activated the PI3K pathway and enhanced the transcription of PDGF-AA, thus promoting tumor angiogenesis. Besides, ANXA3 also promoted EMT and autophagy through the PI3K pathway. These three effects were comprehensively responsible for the roles of ANXA3 in facilitating lenvatinib resistance. What's more, the secreted PDGF-AA could in turn activate the PI3K pathway, thus forming a positive feedback loop, which could amplify the effects driven by ANXA3. Alpelisib is a PI3K inhibitor approved for breast cancer treatment by FDA. We demonstrated that Alpelisib may synergistically improve the antitumor effects of lenvatinib without increasing side effects. This study reports ANXA3 as a biomarker o predict poor prognosis and lenvatinib resistance in HCC. The combined use of Alpelisib and lenvatinib may serve as a potential therapeutic strategy for lenvatinib-resistant HCC.

Curcumin inhibits Annexin A1 signaling to promote neuronal survival and functional recovery after ischemic stroke

ANXA1-FPR1 signaling in myeloid cells drives MASH by elevating S100A4/A11.

The deficiency of circSLC8A1 fosters tubular partial EMT-induced renal fibrosis through upregulating Annexin A2 signaling.