Synergistic effects of estrogen deficiency and articular disk derangement on condylar bone loss.

Objectives: Temporomandibular joint osteoarthritis (TMJ-OA) with condylar resorption is a multifactorial condition involving hormonal imbalance and articular disk dysfunction, often leading to severe TMJ degeneration. This study investigated the combined effects of estrogen deficiency and anterior articular disk derangement (ADD) on condylar bone resorption in a mouse model.

Methods: Female C57BL/6J mice underwent ovariectomy (OVX) to induce estrogen deficiency and ADD was surgically induced for stress.

CD34hi subset of synovial fibroblasts contributes to fibrotic phenotype of human knee osteoarthritis.

Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify the synovial cell subsets responsible for OA pathophysiology by comprehensive analyses of human synovium samples in single-cell resolution. Two distinct OA synovial tissue groups were classified by gene expression profiles in RNA-Seq: inflammatory and fibrotic.

Release of apoptosis inhibitor of macrophage (AIM) from pentameric IgM in serum predicts prognosis after hemodialysis initiation.

Background: The optimal timing for initiating dialysis and prognostic markers in chronic kidney disease (CKD) patients are under debate, with mortality and cardiovascular risks varying among patients. This study investigates whether the apoptosis inhibitor of macrophage (AIM), which is mostly bound to pentameric IgM, could serve as an effective indicator.

Methods: We prospectively followed 423 patients at dialysis initiation and 563 at various CKD stages.

Modeling vascular dynamics at the initial stage of endochondral ossification on a microfluidic chip using a human embryonic-stem-cell-derived organoid.

Vascular interactions play a crucial role in embryogenesis, including skeletal development. During endochondral ossification, vascular networks are formed as mesenchymal cells condense and later invade skeletal elements to form the bone marrow. We and other groups developed a model of endochondral ossification by implanting human embryonic stem cell (hESC)-derived sclerotome into immunodeficient mice.

Predicting the effects of drugs and unveiling their mechanisms of action using an interpretable pharmacodynamic mechanism knowledge graph (IPM-KG).

Background: Multiple studies have aimed to consolidate drug-related data and predict drug effects. However, most of these studies have focused on integrating diverse data through correlation rather than representing them based on the pharmacodynamic mechanism of action (MOA). It is thus crucial to obtain interpretability to validate prediction results.

Re-evaluation of the canonical PAF pathway in cutaneous anaphylaxis.

Platelet-activating factor (PAF) is a potent classical lipid mediator that plays a critical role in various diseases such as allergy and nervous system disorders. In the realm of allergy, previous studies suggested that PAF is generated in response to extracellular stimuli and contributes to allergic reactions via PAF receptor (PAFR). However, the sources of endogenous PAF and its pathophysiological dynamics remain largely elusive in vivo.

Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics.

Sleep is regulated by homeostatic processes, yet the biological basis of sleep pressure that accumulates during wakefulness, triggers sleep, and dissipates during sleep remains elusive. We explored a causal relationship between cellular synaptic strength and electroencephalography delta power indicating macro-level sleep pressure by developing a theoretical framework and a molecular tool to manipulate synaptic strength. The mathematical model predicted that increased synaptic strength promotes the neuronal "down state" and raises the delta power.

An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience.

Breakdown of lipid homeostasis is thought to contribute to pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer's Disease (AD). Cognitive reserve theory posits a role for compensatory mechanisms in the aging brain in preserving neuronal circuit functions, staving off cognitive decline, and mitigating risk for AD. However, the identities of such mechanisms have remained elusive.

Elucidating Nonlinear Stress Relaxation in Transient Networks through Two-Dimensional Rheo-Optics.

This study aims to elucidate the origin of nonlinear stress relaxation behaviors in transient networks using a systematically controlled model system consisting of the tetra-armed polyethylene glycols (Tetra-PEG slime) in conjunction with two-dimensional rheo-optics observations. Transient networks, characterized by their temporary cross-links, are extensively utilized in self-healing and robust materials. However, the molecular mechanisms governing their viscoelastic responses to large deformations have remained elusive.

Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks.

Although previous studies have reported that pre-mRNA splicing factors (SFs) are involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), their exact role in promoting HR remains poorly understood. Here, we showed that SART1, an SF upregulated in several types of cancer, promotes DSB end resection, an essential first step of HR. The resection-promoting function of SART1 requires phosphorylation at threonine 430 and 695 by ATM/ATR.

Efficient topical treatments of cutaneous lupus erythematosus: a systematic review and network -meta-analysis.

Although topical agents have been used to treat cutaneous lupus erythematosus (CLE), there was previously no high-quality evidence of which agents were most effective and which clinical scores were most suitable. On 22 December 2023, a search was conducted across five databases to identify randomized controlled trials (RCTs) for CLE. Two authors independently screened the titles and abstracts of articles based on predetermined criteria.

Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.

Patatin-like phospholipase domain-containing lipase 8 (PNPLA8), one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological processes through the maintenance of membrane phospholipids. Biallelic variants in PNPLA8 have been associated with a range of paediatric neurodegenerative disorders. However, the phenotypic spectrum, genotype-phenotype correlations and the underlying mechanisms are poorly understood.

Extracellular vesicles as a hydrolytic platform of secreted phospholipase A.

Extracellular vesicles (EVs) represent small vesicles secreted from cells, including exosomes (40-150 nm in diameter), which are released via the multivesicular endosomal pathway, and microvesicles and ectosomes (100-1000 nm), which are produced by plasma membrane budding. Broadly, EVs also include vesicles generated from dying cells, such as apoptotic bodies (5-10 μm), as well as exomeres (< 50 nm), which are very small, non-membranous nanoparticles. EVs play important roles in cell-to-cell signaling in various aspects of cancer, immunity, metabolism, and so on by transferring proteins, microRNAs (miRNAs), and metabolites as cargos from donor cells to recipient cells.

Activation of the PGE-EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis.

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology.

Lipid-orchestrated paracrine circuit coordinates mast cell maturation and anaphylaxis through functional interaction with fibroblasts.

Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA, like that of the phospholipase PLA2G3, the prostaglandin D (PGD) synthase L-PGDS, or the PGD receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA.

Transplantation of pancreatic beta-cell spheroids in mice non-swellable hydrogel microwells composed of poly(HEMA--GelMA).

Pancreatic islet transplantation is an effective treatment for type I diabetes mellitus. However, many problems associated with pancreatic islet engraftment remain unresolved. In this study, we developed a hydrogel microwell device for islet implantation, fabricated by crosslinking gelatin-methacryloyl (GelMA) and 2-hydroxyethyl methacrylate (HEMA) in appropriate proportions.

Associations of Subjective Sleep Quality with Wearable Device-Derived Resting Heart Rate During REM Sleep and Non-REM Sleep in a Cohort of Japanese Office Workers.

Background: Associations between subjective sleep quality and stage-specific heart rate (HR) may have important clinical relevance when aiming to optimize sleep and overall health. The majority of previously studies have been performed during short periods under laboratory-based conditions. The aim of this study was to investigate the associations of subjective sleep quality with heart rate during REM sleep (HR REMS) and non-REM sleep (HR NREMS) using a wearable device (Fitbit Versa).