Global Capital, Business Groups and State Coordination: the Changing Profile of Chaebol-State Relations in South Korea

This article examines the effects of global capitalism and state coordination on the financial behaviour of chaebol (business conglomerates) in South Korea. This study focuses on the evolution from controller to coordinator in the post-developmental South Korean state. In recent times, the Korean government has been studied as the exemplar of the Asian newly industrializing economies (NIEs) based on its ability to control economic development. As civil society pressures outgrew government control in the 1990s, the government’s mission shifted from control to coordination – the state sought to accommodate newly emerging or enlarged bargaining domains of key political-economic actors. However, the emergent post-developmental state is buffeted by the growing strength of the private sector, domestically and transnationally. While civil society strived to mobilize mass movements to further social democracy, the neoliberal evolution of capitalist class interests generated institutional configurations favouring the hegemony of finance capital

Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis

Many single-transmembrane proteins are sequentially cleaved by ectodomain-shedding α-secretases and the γ-secretase complex, a process called regulated intramembrane proteolysis (RIP). These cleavages are thought to be spatially and temporally separate. In contrast, we provide evidence for a hitherto unrecognized multiprotease complex containing both α- and γ-secretase. ADAM10 (A10), the principal neuronal α-secretase, interacted and cofractionated with γ-secretase endogenously in cells and mouse brain. A10 immunoprecipitation yielded γ-secretase proteolytic activity and vice versa. In agreement, superresolution microscopy showed that portions of A10 and γ-secretase colocalize. Moreover, multiple γ-secretase inhibitors significantly increased α-secretase processing (r = −0.86) and decreased β-secretase processing of β-amyloid precursor protein. Select members of the tetraspanin web were important both in the association between A10 and γ-secretase and the γ→α feedback mechanism. Portions of endogenous BACE1 coimmunoprecipitated with γ-secretase but not A10, suggesting that β- and α-secretases can form distinct complexes with γ-secretase. Thus, cells possess large multiprotease complexes capable of sequentially and efficiently processing transmembrane substrates through a spatially coordinated RIP mechanism

A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura

Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma

Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease

Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell-cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD

Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer\u27s disease.

Alzheimer\u27s disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell-cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD

Design of a Biomimetic Hydrogel System for Tissue Engineering Application

A hydrogel platform using visible light inducible methacrylated glycol chitosan and riboflavin, an aqueous initiator from natural vitamins is biocompatible and supports proliferation of the encapsulated cells. However, the hydrogel platform has limited cell-matrix interaction, relatively slow degradation, and poor ability to deliver growth factors, which may hinder tissue regeneration. Therefore, the objective of this research is to design a hydrogel system which mimics native extracellular microenvironments, provides tunable degradation, and stabilizes bioactivity of growth factors. The first study explores if the incorporation of native extracellular matrix components in chitosan hydrogel can promote cell-matrix interaction. The hydrogel is functionalized with cell adhesive motifs and cartilaginous or bony matrix. The modified hydrogels increase chondrogenic or osteogenic differentiation of the encapsulated cells by enhancing cell-matrix interaction. This work suggests a hydrogel platform with a specific microenvironment tailored to promote cell differentiation. Tuning hydrogel degradation enables effective and successful tissue regeneration by modulating cellular behaviors and matrix formation. A new degradable hydrogel system is developed based on a unique enzyme-substrate complex, lysozyme-chitosan. Incorporation of lysozyme accelerates hydrogel degradation in a dose dependent manner. This study proposes a novel strategy of incorporating an exogenous enzyme specific to the hydrogel which can control degradation kinetics in a cell-independent manner. Bacterial infection during surgical processes leads to serious complications and continuously results in unsuccessful wound repair. A lysozyme-chitosan conjugate not only allows tunable degradation, but also exhibits antimicrobial properties. The lysozyme modified hydrogels successfully inhibit bacterial growth and delay its proliferation. This work verifies an advanced hydrogel platform with dual functions, tunable degradability and anti-infection.Although heparin is widely used in controlled release system due to its strong binding ability and protective effect for growth factors such as bone morphogenetic protein-2 (BMP-2), it suffers from natural variability, difficulty in modification, and unknown physiological roles. Heparin mimetic sulfonated molecules can do a similar role of heparin by protecting BMP-2 against therapeutically relevant stressors and enhancing its bioactivity. This work demonstrates a new hydrogel system to improve clinical efficacy of BMP-2 and other heparin-binding growth factors. These findings suggest great potentials of material-based therapeutics for tissue engineering application

Design of a Biomimetic Hydrogel System for Tissue Engineering Application

A hydrogel platform using visible light inducible methacrylated glycol chitosan and riboflavin, an aqueous initiator from natural vitamins is biocompatible and supports proliferation of the encapsulated cells. However, the hydrogel platform has limited cell-matrix interaction, relatively slow degradation, and poor ability to deliver growth factors, which may hinder tissue regeneration. Therefore, the objective of this research is to design a hydrogel system which mimics native extracellular microenvironments, provides tunable degradation, and stabilizes bioactivity of growth factors. The first study explores if the incorporation of native extracellular matrix components in chitosan hydrogel can promote cell-matrix interaction. The hydrogel is functionalized with cell adhesive motifs and cartilaginous or bony matrix. The modified hydrogels increase chondrogenic or osteogenic differentiation of the encapsulated cells by enhancing cell-matrix interaction. This work suggests a hydrogel platform with a specific microenvironment tailored to promote cell differentiation. Tuning hydrogel degradation enables effective and successful tissue regeneration by modulating cellular behaviors and matrix formation. A new degradable hydrogel system is developed based on a unique enzyme-substrate complex, lysozyme-chitosan. Incorporation of lysozyme accelerates hydrogel degradation in a dose dependent manner. This study proposes a novel strategy of incorporating an exogenous enzyme specific to the hydrogel which can control degradation kinetics in a cell-independent manner. Bacterial infection during surgical processes leads to serious complications and continuously results in unsuccessful wound repair. A lysozyme-chitosan conjugate not only allows tunable degradation, but also exhibits antimicrobial properties. The lysozyme modified hydrogels successfully inhibit bacterial growth and delay its proliferation. This work verifies an advanced hydrogel platform with dual functions, tunable degradability and anti-infection.Although heparin is widely used in controlled release system due to its strong binding ability and protective effect for growth factors such as bone morphogenetic protein-2 (BMP-2), it suffers from natural variability, difficulty in modification, and unknown physiological roles. Heparin mimetic sulfonated molecules can do a similar role of heparin by protecting BMP-2 against therapeutically relevant stressors and enhancing its bioactivity. This work demonstrates a new hydrogel system to improve clinical efficacy of BMP-2 and other heparin-binding growth factors. These findings suggest great potentials of material-based therapeutics for tissue engineering application