• Molecules and Cells
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• v.42 no.1
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• pp.1-7
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• 2019

Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

• BMB Reports
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• v.52 no.1
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• pp.24-34
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• 2019

Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide.

• Archives of Plastic Surgery
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• v.46 no.3
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• pp.277-281
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• 2019

Recto-vaginal fistulas are difficult to treat due to their high recurrence rate. Currently, no single surgical intervention is universally regarded as the best treatment option for recto-vaginal fistulas. We present a case of recurrent recto-vaginal fistula surgically treated with a gracilis pull-through flap. The surgical goals in this patient were complete excision of the recto-vaginal fistula and introduction of fresh, vascularized muscle to seal the fistula. A defunctioning colostomy was performed 1 month prior to the present procedure. The gracilis muscle and tendon were mobilized, pulled through the freshened recto-vaginal fistula, passed through the anus, and anchored externally. Excess muscle and tendon were trimmed 1 week after the procedure. Follow-up at 4 weeks demonstrated complete mucosal coverage over an intact gracilis muscle, and no leakage. At 8 weeks post-procedure, the patient resumed sexual intercourse with no dyspareunia. At 6 months post-procedure, her stoma was closed. The patient reported transient fecal staining of her vagina after stoma reversal, which resolved with conservative treatment. The fistula had not recurred at 20 months post-procedure. The gracilis pull-through flap is a reliable technique for a scarred vagina with an attenuated recto-vaginal septum. It can function as a well-vascularized tissue plug to promote healing.

• Korean Circulation Journal
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• v.48 no.11
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• pp.974-988
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• 2018

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.2
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.366.1-366.1
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• 2002

Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defective site to initiate de novo tissue regeneration. In this respect. the availability of an appropriate biomaterial scaffold is crucial to allow chondrocyte growth and cartilaginous matrix deposition in a three-dimensional geometry. Hyaluronic acid (HA) molecules are anchored to the chondrocyte membrane via receptors, such as CD44. (omitted)

• Archives of Plastic Surgery
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• v.49 no.5
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• pp.696-700
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• 2022

We performed distal bypass and free flap transfer in a single-stage operation to repair an extensive soft tissue defect in an ischemic foot of an 84-year-old woman. The nutrient artery of the free flap was anastomosed to the bypass graft in an end-to-side manner. Subsequently, the bypass graft became occluded on several occasions. Although intravascular and surgical interventions were performed each time, the bypass graft eventually became completely occluded. However, despite late occlusion of the nutrient artery, the free flap has remained viable and the patient is ambulatory. The time required for a transplanted free flap to become completely viable without a nutrient artery is likely longer for an ischemic foot compared with a healthy foot. However, the exact period of time required is not known. A period of month was required in our patient. We report this case to help clarify the process by which a free flap becomes viable when applied to an ischemic foot.

• BMB Reports
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• v.55 no.2
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• pp.65-71
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• 2022

Regenerative medicine is a research field that develops methods to restore damaged cell or tissue function by regeneration, repair or replacement. Stem cells are the raw material of the body that is ultimately used from the point of view of regenerative medicine, and stem cell therapy uses cells themselves or their derivatives to promote responses to diseases and dysfunctions, the ultimate goal of regenerative medicine. Stem cell-derived extracellular vesicles (EVs) are recognized as an attractive source because they can enrich exogenous microRNAs (miRNAs) by targeting pathological recipient cells for disease therapy and can overcome the obstacles faced by current cell therapy agents. However, there are some limitations that need to be addressed before using miRNA-enriched EVs derived from stem cells for multiplexed therapeutic targeting in many diseases. Here, we review various roles on miRNA-based stem cell EVs that can induce effective and stable functional improvement of stem cell-derived EVs. In addition, we introduce and review the implications of several miRNA-enriched EV therapies improved by multiplexed targeting in diseases involving the circulatory system and nervous system. This systemic review may offer potential roles for stem cell-derived therapeutics with multiplexed targeting.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.12.1-12.17
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• 2024

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.

• Restorative Dentistry and Endodontics
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• v.35 no.1
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• pp.5-12
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• 2010

The purpose of this study was to evaluate the pulp tissue reaction to direct pulp capping of mechanically exposed beagle dogs' pulp with several capping materials. A total of 36 teeth of 2 healthy beagle dongs were used. The mechanically exposed pulps were capped with one of the followings: (1) Mineral Trioxide Aggregate (MTA: $ProRoot^{(R)}$ MTA. Dentsply, Tulsa, USA), (2) Clearfil SE Bond (Dentin adhesive system: Kuraray, Osaka, Japan), (3) Ultra-Blend (Photo-polymerized Calcium hydroxide: Ultradent, South Jordan, USA), (4) Dycal (Quick setting Calcium hydroxide: LD Caulk Co., Milford, USA) at 7, 30, and 90 days before sacrificing. The cavities were restored with Z350 flowable composite resin (3M ESPE, St. Paul. MN, USA). After the beagle dogs were sacrificed, the extracted teeth were fixed, decalcified, prepared for histological examination and stained with HE stain. The pulpal tissue responses to direct pulp capping materials were assessed. In MTA calcium hydroxide, and photo-polymerized calcium hydroxide groups, initial mild inflammatory cell infiltration, newly formed odontoblast-like cell layer and hard tissue bridge formation were observed. Compared with dentin adhesive system, these materials were biocompatible and good for pulp tissue regeneration. In dentin adhesive system group, severe inflammatory cell infiltration, pulp tissue degeneration and pulp tissue necrosis were observed. It seemed evident that application of dentin adhesive system in direct pulp capping of beagle dog teeth cannot lead to acceptable repair of the pulp tissue with dentine bridge formation.