• Journal of Life Science
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• v.31 no.2
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• pp.248-255
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• 2021

Mammary gland tumors are one of the most common cancers in female dogs, and there are various types of cells depending on the tumor type. Complex carcinoma consists of a combination of luminal epithelial and myoepithelial cells with intra-tumoral heterogeneity. However, the origins of these tumor cells and their effects on the malignancies of tumors have not been identified. Recently, it has been reported that cancer stem cells, identified in several types of human tumors, are involved in tumor heterogeneity and may also contribute to malignancies such as tumor recurrence and metastasis. Interestingly, cancer stem cells share several abilities of self-renewal and cell differentiation into multiple types of cancer cells, but they have abnormal genetic mutation and signal transduction pathways to regulate the maintenance of stem cell characters. Moreover, it is known that these cell populations contribute to cell metastasis as well as cell resistance against chemo- and radio-therapeutics that promote tumor recurrence. The existence of cancer stem cells might explain the intra-tumoral heterogeneity and cancer aggressiveness during tumorigenesis in canine mammary gland tumors. This review summarizes the characteristics and types of canine mammary gland tumors, the definition of tumor stem cells, methods of isolation, and clinical significance.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.5
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• pp.339-348
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• 2022

Background: To compare the anesthetic efficacy of supplemental buccal infiltration (BI) (1.7 ml) versus intraligamentary (IL) injection containing 0.4 ml of 4% articaine with 1:100.000 epinephrine after an inferior alveolar nerve block (IANB) with 1.7 ml 2% lidocaine in the first and second mandibular molars diagnosed with irreversible pulpitis (IP). Methods: One hundred subjects diagnosed with IP of either the mandibular first (n = 50) or second molars (n = 50) and failed profound anesthesia following an IANB were selected. They randomly received either the IL or BI techniques of anesthesia. Pain scores on a 170 mm Heft-Parker visual analog scale were recorded initially, before, and during supplemental injections. Furthermore, pulse rate was measured before and after each supplemental injection. During the access cavity preparation and initial filing, no or mild pain was assumed to indicate anesthetic success. The chi-square test, Mann-Whitney U test, and independent samples t-test were used for the analyses. Results: The overall success rates were 80% in the IL group and 74% in the BI group, with no significant difference (P = 0.63). In the first molars, there was no significant difference between the two techniques (P = 0.088). In the second molars, IL injection resulted in a significantly higher success rate (P = 0.017) than BI. IL injection was statistically more successful (P = 0.034) in the second molars (92%) than in the first molars (68%). However, BI was significantly more successful (P = 0.047) in the first molars (88%) than in the second molars (64%). The mean pulse rate increase was significantly higher in the IL group than in the BI group (P < 0.001). Conclusions: Both the IL and BI techniques were advantageous when used as supplemental injections. However, more favorable outcomes were observed when the second molars received IL injection and the first molars received BI.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Journal of Korean society of Dental Hygiene
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• v.23 no.4
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• pp.219-226
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• 2023

Objectives: This study aimed to investigate the effects of rhubarb extract on osteoclast differentiation in bone marrow-derived macrophages (BMMs). Osteoclasts are vital for bone resorption and remodeling. Osteoclast dysregulation can contribute to various bone-related disorders that directly affect oral health. Rhubarb, a medicinal plant with anti-inflammatory properties, has been shown to modulate bone metabolism. Methods: BMMs were isolated from the femurs and tibias of 5-week-old C57BL/6 mice and cultured in the presence of mouse macrophage colony-stimulating factor (M-CSF) for 3 days. Subsequently, BMMs were treated with M-CSF and receptor activator of nuclear factor-κB ligand (RANKL) to induce osteoclast differentiation. Results: Rhubarb extract effectively suppressed osteoclast differentiation in BMMs. Furthermore, rhubarb extract inhibited the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), which are essential for osteoclastogenesis. Moreover, it inhibited the RANKL-induced expression of nuclear factor of activated T cell c1 (NFATc1), a crucial transcription factor in osteoclast differentiation. Conclusions: These results suggest that rhubarb extract promotes oral health by inhibiting osteoclastogenesis in BMMs. Thus, rhubarb extract shows promise as a therapeutic agent for bone-related disorders that directly affect oral health, particularly those associated with abnormal osteoclast activity. Further research and exploration of the underlying mechanisms are warranted to fully understand their potential clinical applications.

• Journal of Korean Foot and Ankle Society
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• v.27 no.4
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• pp.123-130
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• 2023

Purpose: "Hallux valgus" is a common disease encountered in clinical practice and is accompanied by foot deformities. Conservative treatment is commonly used in the early stages of hallux valgus. On the other hand, surgical treatment often becomes necessary as the deformity progresses. Surgical treatments involve various osteotomy methods or joint fusion procedures combined with soft tissue release, and outcomes from these surgical treatments are generally favorable. This study compared two soft tissue release techniques in the hallux region. Materials and Methods: This study conducted a retrospective cohort study on 48 participants who underwent surgical treatment for hallux valgus at a single institution from March 1, 2018, to March 31, 2023. A scarf osteotomy was performed in all cases, and the "Modified Mcbride procedure" or "Trans-articular approach" was done for soft tissue release. Hallux valgus angle (HVA), intermetatarsal angle (IMA), and the degree of subluxation of the lateral sesamoid were measured through simple foot radiographs taken before surgery and one year after surgery. Results: In the Modified Mcbride procedure group, HVA, IMA, and the sesamoid position grade decreased from 34.94° to 9.98°, 15.64° to 5.44°, and 2.47 to 0.44, respectively. In the trans-articular approach group, HVA, IMA, and the sesamoid position grade decreased from 33.42° to 7.34°, 15.06° to 6.03°, and 2.17 to 0.58, respectively. There was no significant difference in these changes between the preoperative and one-year postoperative measurements for both techniques (p-value>0.05). Conclusion: A radiological assessment of soft tissue release through the Modified Mcbride procedure and trans-articular approach in hallux valgus did not show significant differences. Therefore, both surgical techniques can be considered in the distal soft tissue release for a hallux valgus correction.

• Journal of Gastric Cancer
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• v.24 no.3
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• pp.327-340
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• 2024

Purpose: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. Materials and Methods: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). Results: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. Conclusions: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

• Journal of Society of Preventive Korean Medicine
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• v.1 no.1
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• pp.85-104
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• 1997

As the concern about health is increased, the importance of preventive medicine that prevent disease in advance to overcome boundary of disease remedy gets emphasized in the whole world. The fundamental thoughts of oriental medicine are the harmony between the human body and nature, the unified idea regarding mind in the same light with body, and the symmetry of the cosmo dual forces. And oriental medicine is a kind of study that has developed on the ground of prevention thought. from old days, it has been developed the preventive medicine at is called 'Yangseng(養生; recuperation)' etc. with the clinical medicine. The preventive medicine of oriental medicine was taking a serious of the first preventive medicine of an incurable disease thought and the prevention thought that belongs to the second and third preventive medicine is described through the whole oriental medicine. Also the clinical and preventive medicine to apply to the clinics have an in- separable relation. Therefore I inspected the part of the preventive medicine described in some oriental medicine books and studied the characteristics of preventive medicine of oriental medicine as follows; First, the preventive medicine of oriental medicine has the characteristics that is emphasized generally in the first preventive medicine and wholly it is composed in the system of the first, second and third preventive medicine. It has the presentative theory such as 'Jungkijonae sabulkaghan(正氣存內 邪不可干; If good energy is in body, a disease. dosen't occur)', 'Husajukpung Phijeyushi(虛邪賊風 避之有時; When e infectious disease like plague break out, they must avoid the place occurring the disease)', 'Chuninsangeung(天人相應; The harmony of nature and human)' etc.. This is intimately related to the incurable disease thought of the inside diameter and oriental medicine has pursued that. Second, due to the most prerequisite theory of disease production, the balanced condition of environment, the cause of a disease and host is called the health. As oriental medicine has the system of aetiology like that, we can see the host and environments are importance most of all. Namely we can think of the relation of host >> environment > the cause a disease Up to date Jungkijonae Sabulkaghan(正氣存內 邪不可干) that the most oriental medicine doctors have had a knowledge is not whole theory but a pan of oriental medicine science and it is included in oriental medicine theory to avoid infectious disease such as Husajukpung Phijeyushi(虛邪賊風 避之有時). Third, according to the natural result of the first and second contents, we can know that its characteristics stress the remedy without drugs. Because Jungkijonae Sabulkaghan(正氣存內 邪不可干), Husasukpung Phijeyushi(虛邪賊風 避之有時), and Chuninsangeung(天人相應) mean that they prevent disease in condition of freedom from ailment, We can prevent the disease production through the positive preventive methods such as exercise, spirit, food and innate prevention etc.. fourth, the preventive medicine of oriental medicine has developed with therapeutics and it contains all oriental medical methods such as host, environment, exercise, acupuncture and moxibustion, innate or postnatal methods. Also it is the general preventive medicine that has fundamental philosophy of oriental medicine; for examples, the unified idea, the harmony of nature and human, and the unity of mind and body. fifth, to develope the above scientific merit and special features, the preventive medicine of Oriental medicine must be objectified and reemergent stud? gets more and more essential from now on. Especially we need to have the scientific concern of Oriental medicine about the cause of a disease, environmental hygiene, industrial sanitation, and personal hygiene etc..

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.514-521
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• 2007

The sympathetic nerve block improves the blood flow in the innervated regions. For this region, the sympathetic nerve block has been performed in the neural and cerebral disorders. However, the cerebral blood flow regulation of the cranial cervical ganglion block in dogs have not been well defined and the correlation to the changes in the cerebral circulation and the changes in the electroencephalogram is not well defined in dogs yet. Therefore, we investigated the hypothesis that changes in the EEG could be affected by the changes in cerebral blood flow following the cranial cervical ganglion block in dogs. Twenty five beagle dogs were divided into 3 groups; group I(LCCGB, n=10) underwent left sided cranial cervical ganglion block using the 1% lidocaine, group II(L, n=10) injected the 1% lidocaine into the right or left sided digastricus muscle, group III(N/SCCGB, n=5, served as control) underwent the left sided cranial cervical ganglion block using saline. A statistical difference was not found between the control group and the LCCGB group in the 95% spectral edge frequency(SEF) and the median frequency(MF). In the relative band power, the $\delta$ frequency was decreased during 5-25 min, while the $\alpha$ frequency was increased during the same time(p<0.05). But the $\theta$ frequency and the $\beta$ frequency were not shown the significant changes compared with the control group during the same time(p<0.05). These results suggest that the left cranial cervical ganglion block does not induce the change of the cerebral blood flow and its effect is insignificant.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.301-317
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• 2005

The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.