• The Journal of Korean Medical History
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• v.35 no.1
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• pp.1-11
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• 2022

The medical system of the Central Military Command in the late Joseon Dynasty was practiced by military yakbang (clinicians 藥房), acupuncturists, and horse veterinarians. By analyzing and verifying various literatures, the following conclusions were obtained: 1) In the late Joseon Dynasty, military yakbang prioritized internal medical treatment over surgical treatment. Military yakbang were recognized before military acupuncturists were and had more medicinal gardens. This can be associated with the characteristics of the Military Medical Specialized Book that focuses on drug prescription. 2) The positions of military yakbang and military acupuncturists were not preferred by the Western Medical Offices (洋醫司). For example, in the latter days of King Sukjong's reign, positions were appointed from the Western Medical Offices but, on appeal, outside doctors were included as well. This is understood in terms of salary levels and guarantees of career opportunities. 3) The military acupuncturist was not selected based on ability as per the rules. If that was the case, more military acupuncturists would have been selected as royal acupuncturists (內鍼醫) under the system that continued until the late 19th century. In the future, it is expected that comparative studies will be conducted between local military medicine and the early Joseon's military medicine, thereby intensifying research on military medicine in the Joseon Dynasty.

• Korean Circulation Journal
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• v.53 no.1
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• pp.34-46
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• 2023

Background and Objectives: Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF. Methods: DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated. Results: The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed. Conclusions: We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.8.1-8.15
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• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• Journal of Integrative Natural Science
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• v.17 no.1
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• pp.13-20
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• 2024

Female breast cancer is the fifth highest cause of mortality. Breast cancer is the most prevalent type of cancer in women globally, while it can also affect men. STAT5A plays a role in its development and progression. Given that activation of STAT5a is frequently linked to the growth and progression of tumors, STAT5a has been identified as a possible target for the therapy of several cancers. STAT5A, in particular, has proven to be overexpressed in various breast cancer cell lines and tumors, and it has been associated to the promotion of tumour cell proliferation and survival. STAT5A inhibition has been shown in vitro and in vivo to reduce the development of breast cancer cells. As a result, we have screened compounds from the FDA database that might serve as potential inhibitors of STAT5a through virtual screening, docking, DFT and MD simulation approaches. The drug Nilotinib has shown promising results inhibiting STAT5a. Further, in-vitro analysis will be carried forward to understand the anti-cancer activity.

• International Journal of Oral Biology
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• v.49 no.1
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• pp.18-25
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• 2024

Despite advancements in therapeutic approaches, radiotherapy and cisplatin-based chemotherapy remain primary noninvasive treatments for patients with oral squamous cell carcinoma (OSCC). Moreover, the 5-year survival rate for patients with OSCC has remained almost unchanged for several decades, and many side effects of chemotherapy still exist. In this study, three-dimensional (3D) models of OSCC were established using fibroblasts, and the efficacy of various biological inhibitors was evaluated. A culture of epithelial cells with two types of fibroblasts (hTERT-hNOFs and cancer-associated fibroblasts) within a type I collagen matrix resulted in the formation of a continuous layer of tightly packed cells compared to models without fibroblasts. Furthermore, the effects of biological chemicals, including Y27632, latrunculin A, and verteporfin, on these models were investigated. The stratified formation of the epithelial layer and invasion in OSCC 3D-culture models were effectively inhibited by verteporfin, whereas invasion was weakly inhibited by Y27632 and latrunculin. Collectively, the developed OSCC 3D-culture models established with fibroblasts demonstrated the potential for drug screening, with verteporfin showing promising efficacy.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.171-178
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• 2023

Morus alba, a popular medicinal plant belonging to the family Moraceae, has long been used commonly in traditional medicine and has various physiological activities, including antidiabetic, anti-microbial, diuretic, anti-oxidant, and anti-cancer activities. Morusinol was isolated from the root bark of M. alba; however, its biological effects have not yet been reported. Therefore, we examined the inhibitory effects of morusinol on human platelet aggregation, Ca²⁺ mobilization, and αIIb/β₃ activity. Our data showed that collagen-induced human platelet aggregation was inhibited by morusinol without cytotoxicity. In this study, we examined whether morusinol inhibits platelet aggregation through the regulation of integrin αIIb/β₃ and its associated signaling molecules. We observed that morusinol inhibited αIIb/β₃ activation by regulating vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt (protein kinase B), and glycogen synthase kinase-3α/β. These results show that morusinol inhibited fibronectin adhesion, fibrinogen binding, and clot retraction. Taken together, morusinol shows strong antiplatelet and anti-clot retraction effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• International Journal of Stem Cells
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• v.17 no.1
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• pp.80-90
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• 2024

Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated 𝛽-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

• BMB Reports
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• v.57 no.7
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• pp.318-323
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• 2024

Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

• The Korean Journal of Medicine
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• v.99 no.4
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• pp.199-205
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• 2024

Benign small bowel strictures can occur in association with various conditions, including small bowel Crohn's disease, nonsteroidal anti-inflammatory drug-induced enteritis, ischemic enteritis, intestinal tuberculosis, radiation enteritis, postoperative adhesions, and anastomotic strictures. Benign small bowel strictures are classified into two categories, low-grade and high-grade. Low-grade small bowel strictures involve a partial reduction of the internal diameter of the small intestine, causing slight obstruction of the passage of food and digestive fluids without significant bowel obstruction symptoms. By contrast, high-grade small bowel strictures involve a severe narrowing of the intestinal lumen, leading to marked obstruction of the passage of food and digestive fluids and pronounced bowel obstruction symptoms. Small bowel strictures can be diagnosed using various methods, including abdominal plain radiography, abdominal computed tomography, computed tomography enterography, magnetic resonance enterography, balloon-assisted enteroscopy, and abdominal ultrasound. Each diagnostic method has unique advantages and disadvantages as well as differences in diagnostic specificity and sensitivity. Therefore, even if small bowel strictures are not observed using a single imaging technique, their presence cannot be completely excluded. A comprehensive diagnosis that combines clinical information from multiple diagnostic modalities is necessary. Therapeutic approaches for managing small bowel strictures include medical therapy, endoscopic balloon dilation using balloon-assisted enteroscopy, and surgical methods such as strictureplasty and segmental resection. Endoscopic balloon dilation, in particular, can help reduce complications associated with repeated surgeries for strictures.

• Interdisciplinary Bio Central
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• v.1 no.1
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• pp.3.1-3.6
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• 2009

Introduction: GTPases known as translation factor play a vital role as ribosomal subunit assembly chaperone. The bacterial Obg proteins ($Spo{\underline{0B}}$-associated ${\underline{G}}TP$-binding protein) belong to the subfamily of P-loop GTPase proteins and now it is considered as one of the new target for antibacterial drug. The majority of bacterial Obgs have been commonly found to be associated with ribosome, implying that these proteins may play a fundamental role in ribosome assembly or maturation. In addition, one of the experimental evidences suggested that Bacillus subtilis Obg (BsObg) protein binds to the L13 ribosomal protein (BsL13) which is known to be one of the early assembly proteins of the 50S ribosomal subunit in Escherichia coli. In order to investigate binding mode between the BsObg and the BsL13, protein-protein docking simulation was carried out after generating 3D structure of the BsL13 structure using homology modeling method. Materials and Methods: Homology model structure of BsL13 was generated using the EcL13 crystal structure as a template. Protein-protein docking of BsObg protein with ribosomal protein BsL13 was performed by DOT, a macro-molecular docking software, in order to predict a reasonable binding mode. The solvated energy minimization calculation of the docked conformation was carried out to refine the structure. Results and Discussion: The possible binding conformation of BsL13 along with activated Obg fold in BsObg was predicted by computational docking study. The final structure is obtained from the solvated energy minimization. From the analysis, three important H-bond interactions between the Obg fold and the L13 were detected: Obg:Tyr27-L13:Glu32, Obg:Asn76-L13:Glu139, and Obg:Ala136-L13:Glu142. The interaction between the BsObg and BsL13 structures were also analyzed by electrostatic potential calculations to examine the interface surfaces. From the results, the key residues for hydrogen bonding and hydrophobic interaction between the two proteins were predicted. Conclusion and Prospects: In this study, we have focused on the binding mode of the BsObg protein with the ribosomal BsL13 protein. The interaction between the activated Obg and target protein was investigated with protein-protein docking calculations. The binding pattern can be further used as a base for structure-based drug design to find a novel antibacterial drug.