785 results match your criteria: "Center for Disease Biology and Integrative Medicine[Affiliation]"

The trabecular meshwork (TM) cells of the eye are important for controlling intraocular pressure (IOP) and regulating outflow resistance in the aqueous humor. TM cells can remove particles and cellular debris by phagocytosis, decreasing both outflow resistance and IOP. However, the underlying mechanisms remain unclear.

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Subcutaneously Transplanted Fresh Cartilage in Allogeneic and Xenogeneic Immunocompetent Mouse.

Tissue Eng Part A

October 2023

Department of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Cartilage is considered to be immune privileged in general. Clinically, live cells are removed from subcutaneously transplanted allogeneic cartilage mainly for preservation and for infection control. However, because maintaining cartilage feature requires live chondrocyte, it would be beneficial to subcutaneously transplant cartilage with live chondrocyte even if it was allogeneic.

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Metabolic fluxes involving fatty acid biosynthesis play essential roles in controlling the differentiation of T helper 17 (T17) cells. However, the exact enzymes and lipid metabolites involved, as well as their link to promoting the core gene transcriptional signature required for the differentiation of T17 cells, remain largely unknown. From a pooled CRISPR-based screen and unbiased lipidomics analyses, we identified that 1-oleoyl-lysophosphatidylethanolamine could act as a lipid modulator of retinoid-related orphan receptor gamma t (RORγt) activity in T17 cells.

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Coevolution of the ileum with Brk/Ptk6 family kinases confers robustness to ileal homeostasis.

Biochem Biophys Res Commun

October 2023

Laboratory of Microbial Carcinogenesis, Institute of Microbial Chemistry, Microbial Chemistry Research Foundation, Tokyo, 141-0021, Japan; Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan; Center of Infection-associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan. Electronic address:

Brk/Ptk6, Srms, and Frk constitute a Src-related but distinct family of tyrosine kinases called Brk family kinases (BFKs) in higher vertebrates. To date, however, their biological roles have remained largely unknown. In this study, we generated BFK triple-knockout (BFK/TKO) mice lacking all BFK members using CRISPR/Cas9-mediated genome editing.

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Background: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known.

Objective: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP.

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PLA2G2E-mediated lipid metabolism triggers brain-autonomous neural repair after ischemic stroke.

Neuron

October 2023

Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; Department of Neuroinflammation and Repair, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Core Research for Evolutionary Medical Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan. Electronic address:

The brain is generally resistant to regeneration after damage. The cerebral endogenous mechanisms triggering brain self-recovery have remained unclarified to date. We here discovered that the secreted phospholipase PLA2G2E from peri-infarct neurons generated dihomo-γ-linolenic acid (DGLA) as necessary for triggering brain-autonomous neural repair after ischemic brain injury.

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Tissue-Adhesive Hydrogel Spray System for Live Cell Immobilization on Biological Surfaces.

ACS Appl Bio Mater

November 2023

Department of Chemistry & Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.

Gelatin hydrogels are used as three-dimensional cell scaffolds and can be prepared using various methods. One widely accepted approach involves crosslinking gelatin amino groups with poly(ethylene glycol) (PEG) modified with -hydroxysuccinimide ester (PEG-NHS). This method enables the encapsulation of live cells within the hydrogels and also facilitates the adhesion of the hydrogel to biological tissues by crosslinking their surface amino groups.

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Runt-related Transcription Factors and Gene Regulatory Mechanisms in Skeletal Development and Diseases.

Curr Osteoporos Rep

October 2023

Department of Tissue and Developmental Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose Of Review: Runt-related transcription factors (RUNX) play critical roles in skeletal development, metabolism, and diseases. In mammals, three RUNX members, namely RUNX1, RUNX2, and RUNX3, play distinct and redundant roles, although RUNX2 is a dominant factor in skeletal development and several skeletal diseases. This review is to provide an overview of the current understanding of RUNX-mediated transcriptional regulation in different skeletal cell types.

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A Disentangled VAE-BiLSTM Model for Heart Rate Anomaly Detection.

Bioengineering (Basel)

June 2023

Precision Health, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Cardiovascular diseases (CVDs) remain a leading cause of death globally. According to the American Heart Association, approximately 19.1 million deaths were attributed to CVDs in 2020, in particular, ischemic heart disease and stroke.

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Recent advances in micro-sized oxygen carriers inspired by red blood cells.

Sci Technol Adv Mater

June 2023

Department of Chemical System Engineering, The University of Tokyo, Tokyo, Japan.

Supplementing sufficient oxygen to cells is always challenging in biomedical engineering fields such as tissue engineering. Originating from the concept of a 'blood substitute', nano-sized artificial oxygen carriers (AOCs) have been studied for a long time for the optimization of the oxygen supplementation and improvement of hypoxia environments and . When circulating in our bodies, micro-sized human red blood cells (hRBCs) feature a high oxygen capacity, a unique biconcave shape, biomechanical and rheological properties, and low frictional surfaces, making them efficient natural oxygen carriers.

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The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing enzymes exhibiting phospholipase A /A and acyltransferase activities. Plaat3-deficient (Plaat3 ) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high-fat diet (HFD) feeding, while Plaat1 mice have not been analyzed. In the present study, we generated Plaat1 mice and investigated the effects of PLAAT1 deficiency on HFD-induced obesity, hepatic lipid accumulation, and insulin resistance.

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Entrainment is characterized by phase response curves (PRCs), which provide a summary of responses to perturbations at each circadian phase. The synchronization of mammalian circadian clocks is accomplished through the receipt of a variety of inputs from both internal and external time cues. A comprehensive comparison of PRCs for various stimuli in each tissue is required.

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The adeno-associated virus (AAV) is a potent vector for in vivo gene transduction and local therapeutic applications of AAVs, such as for skin ulcers, are expected. Localization of gene expression is important for the safety and efficiency of genetic therapies. We hypothesized that gene expression could be localized by designing biomaterials using poly(ethylene glycol) (PEG) as a carrier.

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The Roles of sPLAs in Skin Homeostasis and Disease.

Biomolecules

April 2023

Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo (UTokyo), 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Among the phospholipase A (PLA) family, the secreted PLA (sPLA) family in mammals contains 11 members that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using knockout and/or transgenic mice for a nearly full set of sPLAs, in combination with comprehensive lipidomics, have revealed the diverse pathophysiological roles of sPLAs in various biological events. Individual sPLAs exert specific functions within tissue microenvironments, likely through the hydrolysis of extracellular phospholipids.

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The development of nanotechnology has been advancing for decades and gained acceleration in the 21st century. Two-dimensional (2D) materials are widely available, giving them a wide range of material platforms for technological study and the advancement of atomic-level applications. The design and application of 2D materials are discussed in this review.

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Article Synopsis
  • Comprehensive genomic profiling (CGP) tests have been available in Japan since June 2019, with over 46,000 patients tested, but they require significant administrative time, averaging 7.6 hours per test.
  • Physicians spend an average of 2.7 hours and nonphysicians 4.9 hours on administrative tasks per patient, with the highest burden from preparing and participating in molecular tumor boards.
  • Core Hospitals incur the highest monthly labor costs (¥3.95 million) compared to Designated and Cooperative Hospitals, emphasizing the need to streamline processes to reduce the administrative workload.
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In some models, animals approach aversive stimuli more than those housed in an enriched environment. Here, we found that male mice in an impoverished and unstimulating (i.e.

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Ultrasound-guided protein delivery is promising for site-specific control of cellular functions in the deep interior of the body in a noninvasive manner. Herein, we propose a method for cytosolic protein delivery based on ultrasound-guided intracellular vaporization of perfluorocarbon nano-droplets. The nano-droplets were conjugated with cargo proteins through a bio-reductively cleavable linker and introduced into living cells via antibody-mediated binding to a cell-surface receptor, which gets internalized through endocytosis.

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The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization.

Cancers (Basel)

March 2023

Department of Dermatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Protein kinases, found in the nucleus and cytoplasm, play essential roles in a multitude of cellular processes, including cell division, proliferation, apoptosis, and signal transduction. STK38 is a member of the protein kinase A (PKA)/PKG/PKC family implicated in regulating cell division and morphogenesis in yeast and . However, its function remained largely unknown in mammals.

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Modulation of immunity by the secreted phospholipase A family.

Immunol Rev

August 2023

Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Article Synopsis
  • - The secreted phospholipase A (sPLA) family, part of the larger PLA superfamily, consists of 11 isoforms in mammals that specifically break down phospholipids into fatty acids and lysophospholipids, indicating they have varied functions based on their tissue distribution.
  • - Research using knockout and transgenic mice has unveiled the roles of sPLA isoforms in immune modulation and associated disorders, highlighting their unique enzymatic specificity and effects in different biological contexts.
  • - sPLAs act on both cell membrane and extracellular phospholipids, influencing disease outcomes, with their effects being context-dependent, and this review synthesizes their roles in immune responses and related health issues.
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Kinase signaling in distinct neuronal populations in the mouse brain controls sleep homeostasis and the circadian clock.

Proc Natl Acad Sci U S A

April 2023

Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

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Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids.

Biochem Biophys Res Commun

May 2023

Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Japan; Laboratory of Neural Information Processing, Institute for Advanced Research, Nagoya University, Japan. Electronic address:

Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs.

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The Lysophospholipase PNPLA7 Controls Hepatic Choline and Methionine Metabolism.

Biomolecules

March 2023

Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Article Synopsis
  • Researchers have discovered the essential role of lysophospholipase PNPLA7 in regulating the production of glycerophosphocholine (GPC) in the liver, which is crucial for methionine metabolism.
  • Mice lacking PNPLA7 show reduced levels of GPC and choline, leading to symptoms similar to methionine deficiency and metabolic changes that mirror those that occur when methionine is depleted in liver cells.
  • The study suggests that lower levels of the methyl donor adenosylmethionine (SAM) can affect PNPLA7 expression, which may have implications for liver cancer, as reduced PNPLA7 and related enzyme levels are seen in human liver cancer cases.
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The circadian clock in the piriform cortex intrinsically tunes daily changes of odor-evoked neural activity.

Commun Biol

March 2023

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

The daily activity in the brain is typically fine-tuned by the circadian clock in the local neurons as well as by the master circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. In the olfactory response, odor-evoked activity in the piriform cortex (PC) and olfactory behavior retain circadian rhythmicity in the absence of the SCN, yet how the circadian rhythm in the PC is achieved independently of the SCN remains elusive. Here, to define neurons regulating the circadian rhythm of the odor-evoked activity in the PC, we knocked out the clock gene Bmal1 in a host of specific neurons along the olfactory circuit.

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Diurnal variation in declarative memory and the involvement of SCOP in cognitive functions in nonhuman primates.

Mol Brain

March 2023

Molecular Biology Section, Center for the Evolutionary Origins of Human Behavior, Kyoto University, Inuyama, Aichi, 484-8506, Japan.

Cognitive functions depend on the time of day in various organisms. Previously, we found that 24-h recognition memory performance of nocturnal mice changes diurnally through SCOP protein-dependent regulation. It remains unknown whether diurnal change and SCOP-dependent regulation of memory performance are conserved across species with diurnal/nocturnal habits.

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