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Jeongmin Lee,Sangwook Lee,Wooram Jung,Guk Bae Kim,Taehun Kim,Jiwon Seong,장혜민,Young Noh,Na Kyung Lee,Boo Rak Lee,Jung-Il Lee,Soo Jin Choi,Wonil Oh,Namkug Kim,Seunghoon Lee,Duk L. Na 대한의학회 2022 Journal of Korean medical science Vol.37 No.31
Background: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. Methods: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. Results: We compared the planned vs. insertion trajectory of IBI to the hippocampus. With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. Conclusion: Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.
Effectiveness of pharmacopuncture for cervical spondylosis: A systematic review and meta-analysis
Lee, Sungyub,Shin, Joon-Shik,Lee, Jinho,Ha, In-Hyuk,Kim, Me-riong,Koh, Wonil,Lee, Sook-Hyun,Kim, Seoyoun,Cha, Yun-Yeop,Lee, Jun-Hwan,Jang, Bo-Hyoung,Lee, Yoon Jae ELSEVIER SCIENCE B.V. 2018 European journal of integrative medicine Vol.20 No.-
Lee, Jeong-Eun,Seo, Inweon,Jeong, Soo-Jin,Koh, Wonil,Jung, Ji Hoon,Kwon, Tae-Rin,Lee, Hyo-Jung,Han, Ihn,Lee, Hyo-Jeong,Lee, Eun-Ok,Kim, Sun-Hyung,Jung, Hee-Jae,Lu, Junxuan,Kim, Sung-Hoon Institute for Advanced Research in Asian Science a 2011 The American journal of Chinese medicine Vol.39 No.6
<P>Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail. Our collaborative team has shown that it has potent anti-angiogenic, anti-cancer and anti-metastatic activities in vivo without observable side effects. We have documented evidence for KMKKT to alleviate drug-induced hematotoxicity in vivo. In the present study, we investigated the mechanistic and signaling events through which KMKKT enhances hematopoiesis, using hematopoietic stem cells (HSCs) isolated from the bone marrow of 8-12 week-old C57BL/6 mice. Our results show that KMKKT significantly increased the expression of the hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in HSCs. KMKKT also increased the expression of c-Kit, a cytokine receptor expressed in HSCs. In addition, KMKKT enhanced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), and increased the binding activity of STAT5 to gamma interferon activated sites (GAS) that mediate JAK2 downstream signaling. Furthermore, we found that KMKKT significantly enhanced the growth rate of colony-forming unit granulocyte erythrocyte monocyte macrophages (CFU-GEMM) and burst forming unit erythroid (BFU-E) of mouse HSCs (mHSCs) stimulated by IL-3/EPO. Overall, our results demonstrated that KMKKT alleviated drug-induced side effects through enhanced hematopoiesis, at least in part through cytokine-mediated JAK2/STAT5 signaling.</P>
Lee, Ju-Young,Joo, Bitna,Nam, Jin Han,Nam, Hye Yeon,Lee, Wonil,Nam, Youngpyo,Seo, Yongtaek,Kang, Hye-Jin,Cho, Hyun-Ji,Jang, Young Pyo,Kim, Jeongyeon,We, Young-Man,Koo, Ja Wook,Hoe, Hyang-Sook Frontiers Media S.A. 2018 FRONTIERS IN AGING NEUROSCIENCE Vol.10 No.-
<P>Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In the present study, we developed ALWPs, a mixture of <I>Antler</I> and LWPs, and investigated whether ALWPs can affect neuroinflammatory responses. We found that ALWPs (500 mg/ml) inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine IL-1β mRNA levels in BV2 microglial cells but not primary astrocytes. ALWPs significantly reduced LPS-induced cell-surface levels of TLR4 to alter neuroinflammation. An examination of the molecular mechanisms by which ALWPs regulate the LPS-induced proinflammatory response revealed that ALWPs significantly downregulated LPS-induced levels of FAK phosphorylation, suggesting that ALWPs modulate FAK signaling to alter LPS-induced IL-1β levels. In addition, treatment with ALWPs followed by LPS resulted in decreased levels of the transcription factor NF-κB in the nucleus compared with LPS alone. Moreover, ALWPs significantly suppressed LPS-induced BV2 microglial cell migration. To examine whether ALWPs modulate learning and memory <I>in vivo</I>, wild-type C57BL/6J mice were orally administered ALWPs (200 mg/kg) or PBS daily for 3 days, intraperitoneally injected (i.p.) with LPS (250 μg/kg) or PBS, and assessed in Y maze and NOR tests. We observed that oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly rescued short- and long-term memory. More importantly, oral administration of ALWPs to LPS-injected wild-type C57BL/6J mice significantly reduced microglial activation in the hippocampus and cortex. Taken together, our results suggest that ALWPs can suppress neuroinflammation-associated cognitive deficits and that ALWPs have potential as a drug for neuroinflammation/neurodegeneration-related diseases, including Alzheimer’s disease (AD).</P>
Lee, Jong-Hwa,Hwang, Kyou-Jung,Kim, Mi-Yeon,Lim, Yeon-Jung,Seol, In-Joon,Jin, Hye-Jin,Jang, Yun-Kyung,Choi, Soo-Jin,Oh, Wonil,Cho, Youl-Hee,Lee, Young-Ho Lippincott Williams Wilkins, Inc. 2012 Journal of pediatric hematology/oncology Vol.34 No.7
Osteoblasts, which are derived from pluripotent mesenchymal stem cells (MSCs), play an important role in hematopoiesis. Human parathyroid hormone (hPTH) induces osteoblasts to produce many factors that are essential to hematopoietic stem cells. However, little is known about the impact of hPTH on MSCs to enhance hematopoiesis. We determined the optimal dose of hPTH that was necessary in vitro for increased osteoblast function. In addition, we compared MSC and osteoblast function to explore the role of hPTH in hematopoiesis. The mRNA expression levels of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 6, stromal cell-derived factor 1, insulin-like growth factor 1 (IGF-1), IGF-2, insulin-like growth factor–binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 were comparable in osteoblasts and human cord blood-derived MSCs. However, G-CSF, GM-CSF, IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3 expression levels in osteoblasts were markedly increased after treatment with 50 or 100 nM of hPTH. In conclusion, hPTH does not affect the ability of MSCs to differentiate into osteoblasts. In addition, hPTH may enhance hematopoiesis by activating the IGF system (IGF-2, IGFBP-1, IGFBP-2, and IGFBP-3) and hematopoietic growth factors (G-CSF and GM-CSF) in osteoblasts, but not in MSCs.
Survey of scrub typhus vectors at epidemic season in Honam region, Korea 2023
Wonil Park,Hyeon Jeong Lee,Eun-Ah Yu,Chi-Kyeong Kim,Wook-Gyo Lee 한국응용곤충학회 2024 한국응용곤충학회 학술대회논문집 Vol.2024 No.04
A surveillance of chigger mites was performed to monitor the incidence of scrub typhus vectors at four environmental collection points in two locations (Sunchang and Haenam) in the Honam region of Korea from August to December 2023. During the surveillance period, 4,174 chigger mites were collected and the predominant species were Leptotrombidium scutellare (94.3%). The density of chigger mites had the peaked at 44 week (10.26~11.1), while the density of patients peaked at 45 week (11.2~11.8) respectively. A positive correlation (r=0.69) observed between scrub typhus patients and vectors. This result suggests that this vector surveillance method will be useful for alarm system of tsutsugamushi disease. However, the relationship between scrub typhus cases and chigger mite density will be studied through long-term periodic surveillance.
Lee, Jae Kwon,Lee, Man Kyoung,Jin, Hye Jin,Kim, Dal-Soo,Yang, Yoon Sun,Oh, Wonil,Yang, Sung-Eun,Park, Tae Seok,Lee, Soo Yeol,Kim, Bum-Soo,Jeun, Sin-Soo Cognizant Communication Corp. 2007 CELL TRANSPLANTATION Vol.16 No.8
<P>Mesenchymal stromal cells (MSCs) are multipotent cells found in several adult tissues; they have the capacity to differentiate into mesodermal, ectodermal, and endodermal tissues in vitro. There have been several reports that MSCs have therapeutic effects in a variety of diseases. Therefore, using a cell labeling technique, monitoring their temporal and spatial migration in vivo, would be useful in the clinical setting. Magnetic resonance imaging (MRI)--tracking of superparamagnetic iron oxide (SPIO)-labeled cells--is a noninvasive technique for determining the location and migration of transplanted cells. In the present study, we evaluated the influence and toxicity of SPIO (ferumoxides) labeling on multiple differentiated MSCs. To evaluate the influence and toxicity of ferumoxides labeling on differentiation of MSCs, a variety of concentrations of ferumoxides were used for labeling MSCs. We found that the cytoplasm of adherent cells was effectively labeled at low concentrations of ferumoxides. Compared with unlabeled controls, the ferumoxides-labeled MSCs exhibited a similar proliferation rate and apoptotic progression. The labeled MSCs differentiated into osteoblasts and adipocytes in an identical fashion as the unlabeled cells. However, chondrogenesis and neurogenesis were inhibited at high concentrations of ferumoxides. Our results suggest the effective concentration for ferumoxides use in tracking MSCs.</P>