A5043476878- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Neurological Disease Mechanisms and Treatments
- Bone Metabolism and Diseases
- Acute Ischemic Stroke Management
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Angiogenesis and VEGF in Cancer
- Neurogenesis and neuroplasticity mechanisms
- Lipoproteins and Cardiovascular Health
- Alzheimer's disease research and treatments
- Pancreatic function and diabetes
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- Viral gastroenteritis research and epidemiology
- Nuclear Receptors and Signaling
- Cardiac Fibrosis and Remodeling
- Neurological Disorders and Treatments
- Bone health and treatments
- Neuroscience and Neuropharmacology Research
- Peripheral Artery Disease Management
Osaka University
2016-2025
Social Welfare Department
2024
The University of Tokyo
2005-2017
Tokyo Medical and Dental University
2017
Hamamatsu University School of Medicine
2011-2014
Kanazawa University
2011-2014
New York University
2014
MIND Research Institute
2014
Cornell University
2008-2014
Chiba University
2013-2014
Background— Subarachnoid hemorrhage caused by the rupture of cerebral aneurysm (CA) remains a life-threatening disease despite recent diagnostic and therapeutic advancements. Recent studies strongly suggest active participation macrophage-mediated chronic inflammatory response in pathogenesis CA. We examined role nuclear factor-κB (NF-κB) CA formation this study. Methods Results— In experimentally induced CAs rats, NF-κB was activated arterial walls early stage with upregulated expression...
Arterial calcification and osteoporosis are associated in postmenopausal women. RANK (the receptor activator of nuclear factor kappaB), RANKL (RANK ligand), osteoprotegerin key proteins bone metabolism have been found at the site aortic calcification. The role these vasculature, as well contribution estrogen to vascular calcification, is poorly understood.To clarify mechanism system context deficiency.RANKL induced inducer morphogenetic protein-2 by human endothelial cells (HAECs) decreased...
Significance Although a high-serum osteoprotegerin (OPG) level is associated with an unfavorable outcome in ischemic stroke, it unclear whether OPG culprit or innocent bystander. Here we show that the deletion of and enhanced RANKL/RANK signaling contribute to reduction infarct volume lower brain edema, whereas increased by reduced −/− mice WT treated anti-RANKL neutralizing antibody. OPG, RANKL, RANK mRNA were expressed activated microglia macrophages. Enhanced showed neuroprotective...
A rapid increase in the number of patients with dementia has emerged as a global health challenge. Accumulating evidence suggests that early diagnosis and timely intervention can delay cognitive decline. The is commonly performed using neuropsychological tests, such Mini-Mental State Examination (MMSE), administered by trained examiners. While these traditional tests are valid reliable, they neither simple nor sufficiently short routine screening tools for dementia. Here, we developed brief...
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4+ CD44high CD62Llow PD-1+ CD153+ accumulate in visceral adipose tissues (VAT) obese individuals. Here, we show the long-lasting effect of using CD153 vaccination remove from high-fat diet (HFD)-induced C57BL/6J mice. We administered a peptide-KLH (keyhole limpet hemocyanin) conjugate vaccine with Alhydrogel (CD153-Alum) or CpG oligodeoxynucleotide (ODN) 1585...
Toll-like receptors (TLRs) and the scavenger receptor CD36 are key molecular sensors for innate immune response to invading pathogens. However, these may also recognize endogenous "danger signals" generated during brain injury, such as cerebral ischemia, trigger a maladaptive inflammatory reaction. Indeed, TLR2 4 involved in inflammation related tissue damage caused by ischemia. Because act coreceptor heterodimers (TLR2/1 or TLR2/6), we tested whether interaction plays role ischemic...
CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates the molecular events underlying reaction that accompanies cerebral ischemia and tissue damage. found activation of nuclear factor-κB, transcription factor coordinates postischemic gene expression, is attenuated CD36-null mice subjected middle artery occlusion. The...
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates expression of low-density lipoprotein (LDL) receptors via receptor internalization and subsequent lysosomal degradation. Thus, an anti-PCSK9 antibody is well known as anti-hyperlipidemia drug. Here, we aimed to develop vaccine for a long-term treatment dyslipidemia targeted PCSK9. In This study, designed peptide mouse PCSK-9, which consisted short peptides conjugated keyhole limpet hemocyanin (KLH) carrier protein. Vaccines were...
Background— Although cerebral occlusive disease leads to ischemic events, an effective treatment has not yet been established. An ideal therapeutic approach treat ischemia might have both aspects of enhancement collateral formation and prevention neuronal death. Hepatocyte growth factor (HGF) is a potent angiogenic that also acts as neurotrophic factor. Thus, in this study, we examined the effects HGF on brain injury rat permanent middle artery occlusion model. Methods Results— Gene transfer...
Objective— Vascular calcification is accelerated by hypertension and also contributes to hypertension; however, it an enigma why vascular are a vicious spiral. The present study elucidates the cross-talk between renin–angiotensin II system receptor activator of nuclear factor-κB ligand (RANKL) in calcification. Approach Results— Angiotensin (Ang) (10 −7 mol/L) significantly increased calcium deposition as assessed Alizarin Red staining, associated with significant increase expression RANKL,...
There is no specific treatment to improve the functional recovery in chronic stage of ischemic stroke. To provide new therapeutic options, we examined effect overexpression hepatocyte growth factor (HGF) cerebral infarction by transferring HGF gene into brain using hemagglutinating virus Japan envelope vector. Sixty rats were exposed permanent middle artery occlusion (day 1). Based on sensorimotor deficits at day 7, divided equally control vector or HGF-treated rats. At 56, transfected with...
Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer's disease in addition infectious diseases. However, before use the clinical setting, vaccines targeting self-antigens must be demonstrated effective safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation self. Although vaccine angiotensin II (Ang II) is efficient rodents humans, little known regarding immunological safety of vaccine. In...
The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention treatment mellitus. Immunization DPP4 vaccine in C57BL/6J mice successfully increased titer, inhibited plasma activity, induced an level. Moreover, this elevated titer was sustained 3 mo. In fed high-fat diet, vaccination...
Decreased adherence to daily ingestion of antiplatelet drugs is a critical issue, increasing mortality and morbidity in poststroke patients. As vaccination could be promising approach solving this, we designed an vaccine that inhibited S100A9 (S100 calcium-binding protein A9)/CD36 (cluster differentiation 36) signaling platelets, which was reported key signal arterial thrombosis, but not hemostasis. Immunization with this induced sustainable increase the anti-S100A9 antibody titer for >2...
Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. The aim of this study was design DNA vaccines for high blood pressure eventually develop human vaccine therapy treat Plasmid vector encoding hepatitis B core-angiotensin II (Ang II) fusion protein injected into spontaneously hypertensive rats using needleless injection system. Anti-Ang antibody successfully produced in core-Ang...
Abstract Despite the recent therapeutic developments for treatment of pulmonary fibrosis, its prognosis is still not well controlled, and a novel agent needed. Recently, critical role Toll-like receptors (TLRs) in pathophysiology fibrosis has been reported; however, effects multiple TLR signaling inhibition are unknown. Here, we examined how TLRs affects using synthetic receptor activator nuclear factor κB ligand (RANKL) partial peptide, MHP1-AcN, which could suppress TLR2, 3, 4, 7, 9...
Estrogen deficiency following menopause increases receptor activator of nuclear factor-kappa B ligand (RANKL) expression in osteoblasts, thereby promoting osteoclast differentiation, and enhances T cell-derived tumor necrosis factor-alpha (TNFα) production, which induces sclerostin osteocytes, inhibiting bone formation. This study aimed to develop a novel uncoupling therapeutic agent for osteoporosis. We developed microglial healing peptide 1 with N-terminal acetylation C-terminal amidation...
The γ-secretase complex (which contains presenilins, nicastrin, anterior pharynx defective-1, and presenilin enhancer-2) cleaves type I transmembrane proteins, including Notch amyloid precursor protein. Dysregulated activity has been implicated in the pathogenesis of Alzheimer's disease, stroke, atherosclerosis, cancer. Tight regulation is required for normal physiology. Here, we isolated HIG1 (hypoxia inducible gene 1, domain member 1A) from a functional screen inhibitory genes. was highly...
Although periostin, an extracellular matrix glycoprotein, plays pivotal roles in survival, migration, and regeneration various cells, its expression function the brain are still unknown. Here, we investigated role of periostin ischemic brain.Expression full-length (periostin 1 [Pn1]) splicing variant lacking exon 17 2 [Pn2]) was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, immunohistochemical staining male C57BL6/J mice. The actions were...