• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5713-5718
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• 2013

Background: DNA methyltransferase-3a (DNMT3a) plays significant roles in embryogenesis and the generation of aberrant methylation in carcinogenesis. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of the DNMT3a gene and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer. Methods: The subjects comprised 447 patients with gastric cancer; 111 individuals with gastric atrophy and 961 healthy controls. Two SNPs (rs1550117 and rs13420827) of the DNMT3a gene were genotyped by Taqman assay. DNMT3a expression was analyzed in cancer tissues from 89 patients by tissue microarray technique. Odds ratio (ORs) and 95% confidence intervals were calculated by multivariate logistic regression. Results: Among healthy controls, risk of H.pylori infection was significantly higher in subjects with the rs1550117 AA genotype, compared to those with GG/AG genotypes of DNMT3a [OR=2.08, (95%CI: 1.02-4.32)]. However, no significant correlation was found between the two SNPs and risk of developing gastric atrophy or gastric cancer. In addition, no increase in DNMT3a expression was observed in the gastric cancer with H.pylori infection. Conclusions: This study revealed that DNMT3a rs1550117 polymorphism is significantly associated with an increased risk of H. pylori infection, but did not support any evidence for contributions of DNMT3a rs1550117 and rs13420827 to either gastric atrophy or gastric cancer. The biological roles of DNMT3a polymorphisms require further investigation.

• 한방재활의학과학회지
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• 제28권4호
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• pp.1-9
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• 2018

Objectives Disuse muscle atrophy occurs in response to pathologies such as joint immobilization, inactivity or bed rest. Muscle disuse is accompanied by an increase in apoptotic signaling, which mediates some of the responses to unloading in the muscle. GB34 (Yanglingquan) is a acupuncture point on the lower leg and one of the most frequently used points in various skeletomuscular diseases. In this study, the hypothesis that the acupuncture at GB34 could attenuate immobilization-induced skeletal muscle atrophy was tested. Methods The left hindlimb immobilization was performed with casting tape in both GB34 group (n=10) and Control group (n=10). The rats in GB34 group were daily treated with acupuncture at GB34. After 2 weeks of immobilization, the morphology of right and left gastrocnemius muscles in both GB34 and Control groups were assessed by hematoxylin and eosin staining. To investigate the immobilization-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. Results GB34 group represented the significant protective effects against the reductions of the left gastrocnemius muscles weight and average cross section area to compared with Control group. The acupuncture at GB34 significantly reduced the immunoreactivity of BAX and increased the immunoreactivity of Bcl-2 in gastrocnemius muscle compared with Control group. Conclusions These results suggest that the acupuncture at GB34 has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle.

• Investigative Magnetic Resonance Imaging
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• 제23권3호
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• pp.228-240
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• 2019

Purpose: The aim of this study is to evaluate the T2 value of the articular cartilage of the glenohumeral joint in rotator cuff disease displayed on 3.0T MRI and to apply it in clinical practice. Materials and Methods: This study involved sixty-two patients who underwent shoulder MRI containing T2 mapping. The mean T2 value was measured by placing a free hand ROI over the glenoid or humeral cartilage from the bone-cartilage interface to the articular surface on three consecutive, oblique coronal images. The drawn ROI was subsequently divided into superior and inferior segments. The assessed mean T2 values of the articular cartilage of the glenohumeral joint were compared and evaluated based on the degree of rotator cuff tear, the degree of fatty atrophy of the rotator cuff, and the acromiohumeral distance. Results: ICC values between two readers indicated moderate or good reproducibility. The mean T2 value for the articular cartilage of the glenoid and humeral head cartilage failed to show any significant difference based on the degree of rotator cuff tear. However, the mean T2 values of articular cartilage, based on fatty atrophy, tended to be higher in fatty atrophy 3 or fatty atrophy 4 groups while some subregions displayed significantly higher mean T2 values. There was no correlation between the acromiohumeral distance and the mean T2 values of the articular cartilage of the glenoid and humeral head. Conclusion: T2 mapping of the glenohumeral joint failed to show any significant difference in quantitative analysis of the degenerative change of the articular cartilage based on the degree of rotator cuff tear. However, it also offers quantitative information on the degenerative change of cartilage of the glenohumeral joint in patients with rotator cuff tear and severe fatty atrophy of the rotator cuff.

• Clinics in Shoulder and Elbow
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• 제22권4호
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• pp.195-202
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• 2019

Background: This study investigates the effects of neuromuscular electrical stimulation (NMES) in preventing deltoid atrophy during the first 12 weeks after arthroscopic rotator cuff repair. Methods: Eighteen patients undergoing arthroscopic repair of a medium-sized rotator cuff tear by a single surgeon, were randomized into two groups: NMES and transcutaneous electrical nerve stimulation (TENS). Each group used the respective device for 6 weeks after surgery. Pain was measured at baseline, 6, and 12 weeks postoperatively, using the visual analogue scale (VAS); range of motion (ROM), abduction strength and functional scores were measured at baseline and 12 weeks postoperatively. Deltoid thickness and cross-sectional areas were measured using magnetic resonance imaging at 12 weeks postoperatively. Results: At 12 weeks post-surgery, no statistically significant difference was observed between the NMES and TENS groups in the pain VAS, the Disabilities of the Arm, Shoulder and Hand score, ROM, and abduction strength. Postoperative decrease in the thickness of the anterior, middle, and posterior deltoid, at the level just below the coracoid, was -2.5%, -0.7%, and -6.8%, respectively, in the NMES group, and -14.0%, -2.6%, and -8.2%, respectively, in the TENS group (p=0.016, p=0.677, and p=0.791, respectively). At the level of the inferior glenoid tubercle, postoperative decrease in area of the deltoid was -5.4% in the NMES group and -14.0% in the TENS group, which was significantly different (p=0.045). Conclusions: NMES has the potential for reducing deltoid atrophy after arthroscopic rotator cuff repair, suggesting that NMES might help minimize postoperative atrophy after various shoulder surgeries.

• 대한한의학방제학회지
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• 제29권1호
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• pp.45-55
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• 2021

Objectives : This study was conducted to evaluate the anti-atrophic effect of polycan in dexamethasone-induced skeletal muscle atrophy in vitro model. Methods : C2C12 myoblast were differentiated into myotube by 2% horese serum medium for 6 days, and then treated polycan extract at different concentrations for 24h. The effect of dexamethasone on the induction of muscle atrophy and expression of atrophy-related genes in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : The results showed that Treatment with polycan (100 and 200 ㎍/㎖) noncytotoxic levels on both myoblast and myotube. Polycan decreased the ROS level overproduced with dexamethasone and improved the depletion of GSH level. Dexamethasone showed a decrease in myotube diameter, which was associated with up-regulation muscle-specific ubiquitin ligases markers, such as atrogin-1, FoxO3, myostatin and muscle RING finger-1 (MuRF1), and down-regulation of myogenin, MEF2, Myogenic regulatory factor 5, 6 and MyoD. The results showed that polycan treatment significantly dose-dependently inhibited it. Furthermore, decreased expressions of PI3K/Akt signal pathway by dexamethasone were reversed by treatment with polycan. Conclusions : Thus, polycan suppresses dexamethasone induced muscle atrophy in C2C12 myotube in vitro model through activation of PI3K/Akt pathway and protective effect of improve skeletal muscle function.

• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1896-1904
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• 2020

Muscle atrophy, characterized by a reduced number and size of myofibers, occurs due to immobilization, aging, and several chronic diseases. Leonurus japonicus, belonging to the Labiatae family, is widely used as a traditional medicine in Korea, China, and Japan. Previous studies have reported that L. japonicus has various physiological activities, such as anti-bacteria, anti-cancer, and liver protection. Leonurine, which is a major bioactive in L. japonicas, is known to possess biological effects including anti-inflammation, anti-fibrosis, anti-angiogenesis, and anti-diabetes. However, the preventive effects of L. japonicas and leonurine on muscle have not been reported. The current study aimed to determine the inhibitory effects of standardized L. japonicus extract (LJE) and leonurine on muscle atrophy by clarifying their underlying molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-stimulated L6 myotubes. LJE and leonurine stimulated the phosphatidylinositol 3-kinase/Akt pathway that was reduced by TNF-α treatment. LJE and leonurine not only increased the mammalian target of rapamycin pathway for protein anabolism but also decreased the mRNA expression of E3 ubiquitin ligases by blocking the translocation of Forkhead box O, which is closely linked with proteolysis. Additionally, LJE and leonurine alleviated inflammatory responses by downregulating TNF-α and interleukin-6 mRNA expression and reducing the protein expression of nuclear factor-kappa B, a major transcriptional factor of proinflammatory cytokines. Collectively, LJE and leonurine have potential as therapeutic candidates for inhibiting the development of skeletal muscle atrophy by activating the PI3K/Akt pathway and reducing inflammatory responses.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.387-396
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• 2022

골격근은 체중의 약 40-50%를 차지하며 자세 유지, 연조직 지지, 체온 유지, 호흡 등 다양한 기능을 수행하는 중요한 조직이다. 전 세계적으로 광범위하게 발생하는 암은 근위축을 동반한 암 악액질을 일으켜 항암제의 효과를 떨어뜨리고 암환자의 삶의 질과 생존율을 크게 떨어뜨린다. 따라서 암 악액질을 개선하기 위한 연구가 진행 중이지만 암과 근육 위축 사이의 연관성에 관한 연구는 거의 없다. 암 세포는 종양 관련 대식세포(TAM), 종양 관련 호중구(TAN) 및 Warburg 효과로 인한 인슐린 저항성을 포함하여 독특한 미세 환경 및 대사를 나타낸다. 따라서 암세포의 미세환경과 대사적 특성, 사이토카인과 인슐린 저항성에 의해 영향을 받을 수 있는 근육 위축의 분자적 기전을 정리하였다. 또한 이는 TAM, TAN, Warburg 효과에 영향을 미치는 물질의 암 악액질 개선 가능성을 시사한다. 본 논문에서는 또한 암 악액질을 개선할 수 있는 단일 화합물 및 이들에 의해 매개되는 신호 전달 경로를 통해 지금까지 확인된 메커니즘을 정리하였다.

• 생명과학회지
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• 제28권4호
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• pp.435-443
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• 2018

AMPK는 세포 내 에너지 균형을 조절하는 조절자 및 에너지 센서이며, 특히 골격근에서는 muscle-specific ubiquitin ligases의 조절을 통한 근육 단백질 분해를 증가시키는 것으로 알려져 있다. 한편 상엽은 다양한 약리학적 효능을 가지는 전통약재 중 하나이지만 근위축과 관련된 효능에 대해서는 거의 알려져 있지 않다. 본 연구에서는 C2C12 myotubes에서 AMPK 활성제인 AICAR가 유발하는 근위축 및 관련 유전자의 발현과 함께 상엽 에탄올 추출물(ethanol extracts of Mori Folium, EEMF)이 유발하는 근위축 억제 효능에 대해서 조사하였다. 먼저 C2C12 myoblasts에 AICAR를 처리하였을 경우 AMPK 활성화가 유발되었으며, 하위 단계에 있는 FoxO3a의 발현 증가와 함께 muscle-specific ubiquitin ligases인 MAFbx/atrogin-1 및 MuRF1의 발현 증가와 muscle-specific transcription factors인 MyoD 및 myogenin의 발현 감소가 유발되었다. 또한 분화가 유발된 C2C12 myotubes에 세포독성이 없는 조건의 AICAR를 처리하였을 경우 근위축이 유발되었으며, EEMF는 AMPK 불활성화 및 FoxO3a 발현 억제를 유발함으로서 AICAR 처리에 의한 근위축을 억제하는 것으로 나타났다. 본 연구 결과에서 AICAR에 의한 AMPK 활성화가 근위축을 유발한다는 것을 알 수 있었으며, EEMF는 AMPK signaling pathway를 통하여 AICAR에 의한 근위축을 억제한다는 것을 알 수 있었다.

• 생명과학회지
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• 제33권3호
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• pp.277-286
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• 2023

스테로이드 유발 근위축은 장기간 코르티코스테로이드 요법의 일반적인 부작용이며 근육량과 기능의 현저한 감소로 이어질 수 있다. 발아된 Rhynchosia Nulubilis (GRH)는 항염증 및 항산화 특성이 있는 것으로 밝혀진 전통적인 약용 식물이다. 그러나 근 감소 억제 효능에 대하여는 보고된 바가 없다. 본 연구에서는 덱사메타손에 의해 유도된 근위축 C2C12 근관세포 모델과 마우스 모델에서 근위축 억제 활성에 대한 GRH의 영향을 평가하였다. 또한 골격근에 대한 GRH 효과의 기본이 되는 분자 경로를 확인하였다. May Grunwald-Giemsa 염색을 통한 근관 세포 염색 결과는 GRH 처리군에서 근관의 길이와 면적이 증가함을 보여주었다. 또한, muscle ring-finger protein-1 (MuRF-1)와 muscle atrophy F-box (MAFbx) 발현이 GRH 처리군에서 유의하게 감소하였다. 더욱이 덱사메타손에 의해 유도된 근위축 C57BL/6 마우스에서 트레드밀을 사용한 지구력 측정과 악력측정기를 이용한 악력 측정을 통한 근육 기능을 평가한 결과 GRH를 경구 투여한 마우스의 근육 기능이 향상되었다. 또한 이러한 결과는 근육 조직에서 GRH에 의한 MAFbx의 발현 억제를 통해 일어남을 확인하였다. 결론적으로 GRH는 MAFbx 발현을 억제하여 유비퀴틴-프로테아좀 경로를 차단함으로써 덱사메타손에 의해 유발된 근위축을 개선할 수 있을 것이다.

• 한국임상수의학회지
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• 제18권1호
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• pp.88-92
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• 2001

A subcutaneous mass foud in a nine-year-old male Iguana (Iguana iguana) was pathologically and microbiologically examined. Grossly, this mass, measuring $2 cm{\times}1.5 cm{\times}1 cm$ in size, contained white to yellow caseous-crumbly material which was surrounded by the thin connective tissue. Histopathologically, a mass consisted of central caseous necrotic debri in which heterophils and macrophages were scattered, and peripheral fibrous connective tissue in which scattered heterophils, macrophages and lymphoid cell aggregates were present. This mass composed of central necrotic core and peripheal connective tissue did not have any detectable microorganisms including acid-fast bacteria and fungi. Histopathologically, severe atrophy of seminiferous tubules in both testicles was observed. In addition, peripheri of ductus deferens was thickened by fibrous connective tissue. This is the first report of subcutaneous caseous necrotic mass of an Iguana in Korea. In addition, the bilateral severe atrophy of seminiferous tubules may be due to fibrosis of ductus deferens.