Development of a diagnostic and drug evaluation system for acute inflammation using a novel [Zr]DTPA-sorbitol probe.

Non-invasive imaging techniques employing biomarkers with high selectivity for inflammation are essential not only for the early diagnosis and prevention of chronic inflammatory diseases but also for guiding appropriate drug therapy and enabling real-time evaluation of anti-inflammatory drug efficacy. In this study, we conjugated radioactive zirconium to sorbitol, a compound that can selectively target inflammation, and evaluated its inflammation-specific uptake and potential for assessing anti-inflammatory treatment efficacy in a mouse inflammation model. Pharmacokinetic analysis demonstrated that radiolabeled sorbitol achieved maximal uptake in inflamed tissues within 1 h.

In Vitro Modeling of Atherosclerosis Using iPSC-Derived Blood Vessel Organoids.

As modeling of atherosclerosis requires recapitulating complex interactions with vasculature and immune cells, previous in vitro models have limitations due to their insufficient 3D vascular structures. However, induced pluripotent stem cell-derived blood vessel organoids (BVOs) are applicable for modeling vascular diseases, containing multiple cell types, including endothelial and vascular smooth muscle cells self-assembled into a blood vessel structure. Atherosclerotic BVOs with a microenvironment associated with atherogenesis, such as shear stress, low-density lipoprotein, pro-inflammatory cytokine, and monocyte co-culture are successfully developed.

CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment.

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment.

Canine amniotic membrane-derived mesenchymal stem cells ameliorate atopic dermatitis through regeneration and immunomodulation.

Mesenchymal stem cells (MSCs) are a promising tool for treating immune disorders. However, the immunomodulatory effects of canine MSCs compared with other commercialized biologics for treating immune disorders have not been well studied. In this study we investigated the characteristics and immunomodulatory effects of canine amnion membrane (cAM)-MSCs.

The Effect of a Novel Mica Nanoparticle, STB-MP, on an Alzheimer's Disease Patient-Induced PSC-Derived Cortical Brain Organoid Model.

Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases, with a substantial amount of advancements in the field of neuroscience and AD. Despite such progress, there has been no significant improvement in AD treatments. To improve in developing a research platform for AD treatment, AD patient-derived induced pluripotent stem cell (iPSC) was employed to generate cortical brain organoids, expressing AD phenotypes, with the accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau (pTau).

Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation.

Decellularized extracellular matrix scaffold, widely utilized for organ engineering, often undergoes matrix decomposition after transplantation and produces byproducts that cause inflammation, leading to clinical failure. Here we propose a strategy using nano-graphene oxide to modify the biophysical properties of decellularized liver scaffolds. Notably, we demonstrate that scaffolds crosslinked with nano-graphene oxide show high resistance to enzymatic degradation via direct inhibition of matrix metalloproteinase activity and increased mechanical rigidity.

Cortical-blood vessel assembloids exhibit Alzheimer's disease phenotypes by activating glia after SARS-CoV-2 infection.

A correlation between COVID-19 and Alzheimer's disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARS-CoV-2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to systemic inflammation including direct cell death.

Combined Orobol-Bentonite Composite Formulation for Effective Topical Skin Targeted Therapy in Mouse Model.

Purpose: Orobol is an isoflavone that has a potent skin protection effect. The objective of this study was to prepare a novel bentonite-based composite formulation of orobol to enhance topical skin delivery.

Methods: The composition was optimized based on the orobol content in the composite and the in vitro release studies, followed by the in vitro and in vivo hairless mouse skin deposition studies.

Preventive effects of nano-graphene oxide against Parkinson's disease via reactive oxygen species scavenging and anti-inflammation.

We investigated the neuroprotective effects of deca nano-graphene oxide (daNGO) against reactive oxygen species (ROS) and inflammation in the human neuroblastoma cell line SH-SY5Y and in the 6-hydroxydopamine (6-OHDA) induced Parkinsonian rat model. An MTT assay was performed to measure cell viability in vitro in the presence of 6-OHDA and/or daNGO. The intracellular ROS level was quantified using 2',7'-dichlorofluorescein diacetate.

LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known to be able to modulate immune responses, possess tissue-protective properties, and exhibit healing capacities with therapeutic potential for various diseases. The ability of MSCs to secrete various cytokines and growth factors provides new insights into autoimmune-diseases such as rheumatoid arthritis (RA). RA is a systemic autoimmune disease that affects the lining of synovial joints, causing stiffness, pain, inflammation, and joint erosion.

Anti-apoptotic Splicing Variant of AIMP2 Recover Mutant SOD1-Induced Neuronal Cell Death.

Although a couple of studies have reported that mutant superoxide dismutase 1 (SOD1), one of the causative genes of familial amyotrophic lateral, interacts physically with lysyl-tRNA synthetase (KARS1) by a gain of function, there is limited evidence regarding the detailed mechanism about how the interaction leads to neuronal cell death. Our results indicated that the aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) mediated cell death upon the interplay between mutant SOD1 and KARS1 in ALS. Binding of mutant SOD1 with KARS1 led to the release of AIMP2 from its original binding partner KARS1, and the free form of AIMP2 induced TRAF2 degradation followed by TNF-α-induced cell death.

Wnt-activating human skin organoid model of atopic dermatitis induced by and its protective effects by .

A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular aggregates with an inside-out morphology with unintended off-target development of cartilage. Here, we first demonstrated that Wnt signaling activation resulted in larger organoids without off-target cartilage.

Enhanced delivery to brain using sonosensitive liposome and microbubble with focused ultrasound.

Glioblastoma is considered one of the most aggressive and dangerous brain tumors. However, treatment of GBM has been still challenged due to blood-brain barrier (BBB). BBB prevents that the chemotherapeutic molecules are extravasated to brain.

All-in-one microfluidic design to integrate vascularized tumor spheroid into high-throughput platform.

The development of a scalable and highly reproducible in vitro tumor microenvironment (TME) platform still sheds light on new insights into cancer metastasis mechanisms and anticancer therapeutic strategies. Here, we present an all-in-one injection molded plastic array three-dimensional culture platform (All-in-One-IMPACT) that integrates vascularized tumor spheroids for highly reproducible, high-throughput experimentation. This device allows the formation of self-assembled cell spheroids on a chip by applying the hanging drop method to the cell culture channel.

Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.

Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by β-amyloid (Aβ) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigger AD pathological features, including Aβ and p-Tau expression.

Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid.

Background And Objectives: Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids.

Immunomodulatory Effect of Epidermal Growth Factor Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Atopic Dermatitis.

Background And Objectives: Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously.

Combined Mesenchymal Stem Cells and Cartilage Acellular Matrix Injection Therapy for Osteoarthritis in Goats.

Background: Human umbilical cord blood-derived MSCs (hUCB-MSCs) have been studied in osteoarthritis (OA) and cartilage regeneration. Our previous study demonstrated that hUCB-MSCs combined with cartilage acellular matrix injection (CAM Inj.) represent potential therapeutic agents for structural improvement and anti-inflammatory effects in a rabbit model of OA.

Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer's disease.

Mitochondrial dysfunction is associated with familial Alzheimer's disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to disease progression. In the amyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by β-secretase to generate a C-terminal fragment, which is then cleaved by γ-secretase to produce amyloid-beta (Aβ). The accumulation of Aβ and its detrimental effect on mitochondrial function are well known, yet the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) contributing to this pathology have rarely been reported.

Vascularization of iNSC spheroid in a 3D spheroid-on-a-chip platform enhances neural maturation.

In vitro platforms for studying the human brain have been developed, and brain organoids derived from stem cells have been studied. However, current organoid models lack three-dimensional (3D) vascular networks, limiting organoid proliferation, differentiation, and apoptosis. In this study, we created a 3D model of vascularized spheroid cells using an injection-molded microfluidic chip.