Publications by authors named "Rikinari Hanayama"

The leukocyte immunoglobulin-like receptor (LILR) family, a group of primate-specific immunoreceptors, is widely expressed on most immune cells and regulates immune responses through interactions with various ligands. The inhibitory type, LILRB, has been extensively studied, and many ligands, such as HLA class I, have been identified. However, the activating type, LILRA, is less understood.

View Article and Find Full Text PDF
Article Synopsis
  • Cells use exosomes, which are small vesicles released from multivesicular bodies, to communicate with other cells, and recent research links their formation to autophagy, but the exact mechanisms are still unclear.
  • A study highlighted that Rubicon, a protein that negatively regulates autophagy, is crucial for the release of exosomes by recruiting another protein, WIPI2d, to enhance their formation.
  • The findings also showed that Rubicon plays a significant role in the age-related increase in exosome release in mice and influences the types of microRNAs found in exosomes, which are related to aging and longevity.
View Article and Find Full Text PDF
Article Synopsis
  • A 74-year-old man with severe aplastic anaemia achieved a long-term remission due to the growth of HLA allele-deficient clones, despite initial treatment complications.
  • After starting eltrombopag and ciclosporin, his blood counts eventually normalized over a span of 3 years, showing a complete recovery of blood cell production.
  • Research techniques like flow cytometry and deep sequencing indicated that his recovery relied on clones with mutations that interfered with antigen presentation, demonstrating a potential new approach for managing immune-related aplastic anaemia in similar patients.
View Article and Find Full Text PDF

Extracellular vesicles (EVs) serve as an intrinsic system for delivering functional molecules within our body, playing significant roles in diverse physiological phenomena and diseases. Both native and engineered EVs are currently the subject of extensive research as promising therapeutics and drug delivery systems, primarily due to their remarkable attributes, such as targeting capabilities, biocompatibility, and low immunogenicity and mutagenicity. Nevertheless, their clinical application is still a long way off owing to multiple limitations.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers studied leukocyte immunoglobulin-like receptors (LILRs) on chromosome 19, which show genetic variations across human populations and have complex genomic regions that are hard to characterize.
  • They used a tool called JoGo-LILR CN Caller to analyze data from over 2,500 whole genome sequencing samples, discovering a novel large deletion in the Japanese population that affects three genes.
  • This deletion creates a hybrid gene combining parts of two LILR genes, leading to potentially new signaling functions, with similar hybrid genes also identified in another population sample.
View Article and Find Full Text PDF

In addition to cross-presentation, cross-dressing plays an important role in the induction of CD8 T cell immunity. In the process of cross-dressing, conventional dendritic cells (DCs) acquire major histocompatibility complex class I (MHCI) from other cells and subsequently prime CD8 T cells via the pre-formed antigen-MHCI complexes without antigen processing. However, the mechanisms underlying the cross-dressing pathway, as well as the relative contributions of cross-presentation and cross-dressing to CD8 T cell priming are not fully understood.

View Article and Find Full Text PDF

Methods that enable specific and sensitive quantification of small extracellular vesicles (sEVs) using flow cytometry are still under development. Aggregation or adsorption of antibodies causes sub-nano sized particles or non-specific binding and largely affects the results of flow cytometric analysis of single sEVs. Comparison of control IgG and target-specific IgG is inappropriate because they have different characters.

View Article and Find Full Text PDF

Amorphous silica has been approved as a food and pharmaceutical additive. However, its potential to enhance the carcinogenicity of epithelial cells is incontrovertible. With their expanded surface area per unit mass and distinctive cellular incorporation, nano-sized silica particles (nSPs) exhibit heightened cytotoxicity compared to micrometer-sized counterparts.

View Article and Find Full Text PDF

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) cells have high metastatic potential. Recent research has revealed that the interaction of between tumor cells and the surrounding stroma plays an important role in tumor invasion and metastasis. In this study, we showed the prognostic value of expression of SPARC, an extracellular matrix protein with multiple cellular functions, in normal adjacent tissues (NAT) surrounding NPC.

View Article and Find Full Text PDF

Scanning ion conductance microscopy (SICM) is a promising tool for visualizing the dynamics of nanoscale cell surface topography. However, there are still no guidelines for fabricating nanopipettes with ideal shape consisting of small apertures and thin glass walls. Therefore, most of the SICM imaging has been at a standstill at the submicron scale.

View Article and Find Full Text PDF

In our previous study, osteosarcoma advanced locally, and metastasis was promoted through the secretion of large number of small extracellular vesicles, followed by suppressing osteoclastogenesis via the upregulation of microRNA (miR)-146a-5p. An additional 12 miRNAs in small extracellular vesicles were also detected ≥6× as frequently in high-grade malignancy with the capacity to metastasize as in those with a low metastatic potential. However, the utility of these 13 miRNAs for determining the prognosis or diagnosis of osteosarcoma has not been validated in the clinical setting.

View Article and Find Full Text PDF

Anti-spike neutralizing antibodies (S NAbs) have been developed for prevention and treatment against COVID-19. The nanoscopic characterization of the dynamic interaction between spike proteins and S NAbs remains difficult. By using high-speed atomic force microscopy (HS-AFM), we elucidate the molecular property of an S NAb and its interaction with spike proteins.

View Article and Find Full Text PDF

Small extracellular vesicles (sEVs) play a crucial role in local and distant cell communication. The intrinsic properties of sEVs make them compatible biomaterials for drug delivery, vaccines, and theranostic nanoparticles. Although sEV proteomics have been robustly studied, a direct instantaneous assessment of sEV structure dynamics remains difficult.

View Article and Find Full Text PDF

Purpose: To inhibit the transmission of SARS-CoV-2, we developed engineered exosomes that were conjugated with anti-spike nanobodies and type I interferon β (IFN-β). We evaluated the efficacy and potency of nanobody-IFN-β conjugated exosomes to treatment of SARS-CoV-2 infection.

Methods: Milk fat globule epidermal growth factor 8 (MFG-E8) is a glycoprotein that binds to phosphatidylserine (PS) exposed on the exosomes.

View Article and Find Full Text PDF

Small extracellular vesicles (SEVs) secreted from various cells are lipid bilayer vesicles, 30-150 nm in size, that carry proteins, nucleic acids, and lipids as cargos to other cells. They include exosomes, which are generated in multivesicular endosomes (MVEs) and secreted upon fusion of MVEs with plasma membranes and a part of microvesicles, which directly bud from plasma membranes. SEVs have attracted attention as diagnostic and drug discovery targets, since it has been demonstrated that SEVs are involved in the intercellular communication in many diseases and physiological phenomena such as cancer, neurodegenerative diseases, and immunity.

View Article and Find Full Text PDF
Article Synopsis
  • SARS-CoV-2 spike protein binds to the human ACE2 receptor, enabling virus entry into cells; this study uses high-speed atomic force microscopy (HS-AFM) to visualize this interaction in real time.
  • The findings reveal that the spike protein has flexible regions and can change shape in response to pH and temperature; the S-ACE2 complex adopts a specific conformation that changes under acidic conditions.
  • Different mechanisms are observed for the spike protein and its S2 subunit when docking onto small extracellular vesicles (sEVs), suggesting potential strategies for developing viral entry inhibitors and neutralizing agents.
View Article and Find Full Text PDF

Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell-cell communication by transporting proteins, lipids, and nucleic acids. As the involvement of EVs in diseases has become apparent, druggable regulators of EV secretion are required. However, the lack of a highly sensitive EV detection system has made the development of EV regulators difficult.

View Article and Find Full Text PDF

Osteosarcoma is the most frequent type of primary bone tumor in children and adolescents, thus care for patients with malignant osteosarcoma is strongly required. The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients.

View Article and Find Full Text PDF

Exosomes have recently gained interest as mediators of cell-to-cell communication and as potential biomarkers for cancer and other diseases. They also have potential as nanocarriers for drug delivery systems. Therefore, detailed structural, molecular, and biomechanical characterization of exosomes is of great importance for developing methods to detect and identify the changes associated with the presence of cancer and other diseases.

View Article and Find Full Text PDF

Accumulating evidence indicates the presence of cytoplasmic DNAs in various types of malignant cells, and its involvement in anti-cancer drug- or radiotherapy-mediated DNA damage response and replication stress. However, the pathophysiological roles of cytoplasmic DNAs in leukemias remain largely unknown. We observed that during hematopoietic stem cell transplantation (HSCT) in mouse myeloid leukemia models, double-stranded (ds)DNAs were constitutively secreted in the form of extracellular vesicles (EVs) from myeloid leukemia cells and were transferred to the donor cells to dampen their hematopoietic capabilities.

View Article and Find Full Text PDF

Leukocyte immunoglobulin (Ig)-like receptors (LILRs) are encoded by members of a human multigene family, comprising 11 protein-coding genes and two pseudogenes. Among the LILRs, LILRB3 and LILRA6 show the highest homology with each other, along with high allelic and copy number variations. Therefore, it has been difficult to discriminate between them, both genetically and functionally, precluding disease association studies of LILRB3 and LILRA6.

View Article and Find Full Text PDF

Cancer-associated cachexia (CAC) is a common syndrome in cancer patients and is characterized by loss of body weight accompanied by the atrophy of fat and skeletal muscle. Metabolic changes are a critical factor in CAC; however, the mechanisms through which tumors inhibit adipogenesis and promote lipolysis are poorly understood. To clarify these mechanisms, we investigated adipogenesis-limiting factors released by tumors in a cell culture system.

View Article and Find Full Text PDF

Extracellular vesicles (EVs), such as exosomes and microvesicles, are small membrane vesicles secreted by almost all cell types and are abundant in blood, body fluids, such as urine, spinal fluid, tears and saliva, and cell culture media. From an evolutionary perspective, they are biologically significant as a means for expelling unwanted cellular contents. Recently, EVs have received considerable attention as messengers of intercellular communication networks, allowing the exchange of proteins and lipids between the cells producing them and target cells that trigger various cellular responses.

View Article and Find Full Text PDF
Article Synopsis
  • Drug tolerance in EGFR mutated lung cancer cells leads to acquired resistance against EGFR-TKIs like osimertinib, despite the reasons for this phenomenon being unclear.
  • AXL-low expressing EGFR-mutated lung cancer cells show more sensitivity to osimertinib, but a small population can develop tolerance through increased IGF-1R expression, influenced by its transcription factor FOXA1.
  • Combining transient IGF-1R inhibition with ongoing osimertinib treatment has been shown to eliminate tumors and prevent regrowth in both cell-derived and patient-derived xenograft models, suggesting a potential strategy to enhance treatment efficacy.
View Article and Find Full Text PDF