Natural products have recently emerged as promising candidates for anticancer therapeutics. However, research on their use as adjuvants to existing chemotherapeutic agents in the treatment of oral squamous cell carcinoma (OSCC) remains limited. This study investigated the potential of METO, a methanol extract derived from Thuja orientalis, to induce apoptosis and its underlying mechanisms in the OSCC cell line HSC4. The results demonstrated that METO induces apoptosis in HSC4 cells, which is likely mediated through the activation of the ERK and JNK pathways, both of which were observed to be activated in METO-treated cells. Additionally, METO-induced apoptosis appears to involve signaling pathways associated with SOCS3 and p53. These findings highlight that METO exhibits strong anticancer activity in OSCC cells and suggest its potential as a promising chemotherapeutic agent for OSCC treatment.
Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro . However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca2+ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca2+ ([Ca2+]i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca2+]i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca2+ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca2+ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca2+]i mobilization, we identified modified expression levels of Ca2+ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca2+]i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.
Many Korean domestic masonry structures constructed since 1970 have been found to be vulnerable to earthquakes because they lack efficient lateral force resistance. Many studies have shown that the brick and mortar suddenly experience brittle fracture and out-of-plane collapse when they reach the inelastic range. This study evaluated the seismic retrofitting of non-reinforced masonry with Hybrid Super Coating (HSC) and Cast, manufactured using glass fiber. Four types of specimen original specimen (BR-OR), one layered HSC (BR-HS-O), two-layered HSC (BR-HS-B), one layered HSC, and Cast (BR-CT-HS-O) were constructed and analyzed using compression, flexural tensile, diagonal compression, and triplet tests. The specimen responses were presented and discussed in load-displacement curves, maximum strength, and crack propagation. The compressive strength of the retrofit specimens slightly increased, while the flexural tensile strength of the retrofit specimens increased significantly. In addition, the HSC and Cast also produced a considerable increase in the ductile response of specimens before failure. Diagonal compression test results showed that HSC delayed brittle cracks between the mortar and bricks and resulted in larger displacement before failure than the original brick. The triplet test results confirmed that the bonding strength of the retrofit specimens also increased. The application of HSC and Cast was found to restrain the occurrence of brittle failure effectively and delayed the collapse of masonry wall structures.
Human melatonin receptors consist of melatonin receptor 1A (MT1) and melatonin receptor 1B (MT2), and possess various biological activations, which include the control of circadian rhythm and immune regulation. Recently, it have been found that melatonin receptors inhibit cell proliferation and have oncostatic properties, which is being researched in the treatment strategies of breast cancer, prostate cancer, and Non-Small Cell Lung Cancer. Also, interest in the effect of melatonin receptor’s correlation to head and neck carcinogenesis and application possibilities on head and neck cancer has been found. However, in head and neck cancer, how melatonin receptor relates and functions with epithelial-mesenchymal transition (EMT), which plays a major role in human carcinogenesis, is yet unknown. In this research, in HSC5 cell and YD15 cell, the head and neck cancer cell lines, a selective melatonin receptor antagonist, Luzindole, was utilized to examine the effect of melatonin receptors on EMT. After treating Luzindole on HSC5 cells and YD15 cells, the authors evaluated cell viability rate with CCK 8 assay, and performing colony forming assay, invasion assay and western blot analysis, to confirm melatonin receptor’s effect on EMT. When Luzindole was treated on HSC5 cells and YD15 cells in low concentration of 100nM, no significant difference in cell viability was found, whereas Luzindole-treated cells had a significantly increase in the invasion assay. As a result of colony forming assay, in YD15 cells, the number of colony formation decreased slightly, whereas in HSC3 cells, the number of colony formation increased. According to the western blotting, no difference in E-cadherin, Slug, and vimentin protein expression was shown. This result of research indicates the possibility of melatonin receptor being related to EMT and new chemotherapeutic target in the carcinogenesis of head and neck cancer.
Autophagy is recently receiving the spotlight as the development strategy for promising anticancer drugs. In particular, the majority of anticancer drugs originating from natural products are known to induce autophagy. Saururus chinensis has been used for treating various inflammatory diseases. Recent research has revealed that the extract of Saururus chinensis possess cytotoxicity for various types of human cancer cells. However, the exact action mechanism of Saururus chinensis extract for oral squamous cell carcinoma (OSCC) has not been studied yet. Therefore, the authors of this research aim to study the effect of methanol extract of S. chinensis (MESC) on OSCC cells. To observe the cell proliferation inhibitory effect of MESC on HSC3 cells, the authors conducted the trypan blue exclusion assay. Also, the action mechanism of MESC was studied by conducting the cell cycle analysis, acidic vesicular organelle (AVO) staining and flow cytometry analysis, monodansylcadaverine (MDC) staining, propidium iodide staining, and Western blotting on MESC-treated HSC3 cells. When HSC3 cells were treated in MESC, the cell proliferation was suppressed in time-dependent and dose-dependent manners. Also, the number of sub-G1 arrested cells increased in a dose-dependent manner. MDC punctate and AVO puncta significantly increased respectively. Western blot analysis demonstrated the expression of autophagy-related proteins increased, but apoptotic proteins were not observed. Also, the pAkt protein was reduced, while the p-p38 protein and pERK protein increased. According to our results, MESC induced autophagy and accompanied changes in the cell cycle in HSC3 cells. Also, the alteration in Akt, ERK, and p38 pathways were confirmed. This result suggested the possibility of MESC as the new promising adjuvant for treating OSCC patients.
β-phenylethyl isothiocyanate(PEITC) is a component derived from cruciferous vegetables and has been demonstrated to fight many types of cancers through various molecular pathways. In the present study, we focused on its effect on the induction of apoptotic cell death to inhibit cell growth and its molecular mechanism in HSC-4 human oral cancer cells. A colorimetric MTS assay was used to examine cell viability. The apoptotic effect and was investigated using DAPI staining and the molecular target and mechanism of PEITC-mediated apoptosis were determined by Western blotting. The result showed that PEITC inhibited oral cancer cell growth and induced apoptosis via extrinsic signaling pathway evidenced by the activation of caspase 8, truncation of bid protein and induction of death receptor(DR) 5. DR5 protein level was increased through the activation of p38 and c-Jun N-terminal kinase(JNK). These results from this study strongly suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 and JNK.
Mosquito-borne viral pathogens infect millions of people worldwide, often resulting in fatal infections. Our research interests in mosquito vector biology focuses on understanding of the molecular and genetic basis of mosquito resistance to arbovirus infections. Unlike mammalian cells including humans, for instance, mosquito cells do not show pathologic symptoms when infected by arboviruses. This observation led us to embarking a microarray study to investigate mosquito-virus interactions using Anopheles gambiae and o’nyong-nyong virus (ONNV) as a model system. As a result, we found that transcription of the hsc70B gene is increased about 2.6-fold in ONNV-infected An. gambiae compared to non-infected controls. Subsequently, in vivo RNAi silencing of the hsc70B transcript caused enhanced ONNV replication in female mosquitoes. Therefore, these results suggest that the hsc70B protein has an inhibitory effect on ONNV replication. A promoter analysis of the hsc70B locus further demonstrated that the hsc70B promoter is able to induce transcription of hsc70B in response to ONNV infection. In addition, hsc70B transcription was also induced by West Nile or La Crosse virus infection. Collectively, our findings indicate that hsc70B plays a role in suppressing virus replication as a general antiviral mechanism. Implications of hsc70B research and our other research endeavors toward the control of mosquito-borne infectious diseases will be discussed.
Cytosolic Ca2+ is an important regulator of tumor cell proliferation and metastasis. Recently, the strategy of blocking receptors and channels specific to certain cancer cell types has emerged as a potentially viable future treatment. Oral squamous cell carcinoma is an aggressive form of cancer with a high metastasis rate but the receptor-mechanisms involved in Ca2+ signaling in these tumors have not yet been elucidated. In our present study, we report that bradykinin induces Ca2+ signaling and its modulation in the human oral squamous carcinoma cell line, HSC-3. Bradykinin was found to increase the cytosolic Ca2+ levels in a concentration-dependent manner. This increase was inhibited by pretreatment with the phospholipase C-β inhibitor, U73122, and also by 2-aminoethoxydiphenyl borate, an inhibitor of the inositol 1,4,5-trisphosphate receptor. Pretreatment with extracellular ATP also inhibited the peak bradykinin-induced Ca2+ rise. In contrast, the ATP-induced rise in cytosolic Ca2+ was not affected by pretreatment with bradykinin. Pretreatment of the cells with either forskolin or phorbol 12-myristate 13-acetate (activators of adenylyl cyclase and protein kinase C, respectively) prior to bradykinin application accelerated the recovery of cytosolic Ca2+ to baseline levels. These data suggest that bradykinin receptors are functional in Ca2+ signaling in HSC-3 cells and may therefore represent a future target in treatment strategies for human oral squamous cell carcinoma.
Root-knot nematode damage was found on yam, Dioscorea bulbifera in Andong Korea. From the root-knots, female nematodes were isolated and subjected to DNA sequence analysis. Sequence of cytochrome oxidase subunit Ⅱ (COII) was analyzed from the genomic DNA of the isolate. COII locus size and sequence of the nematode isolate were similar to those of Meloidogyne javanica or M. incognita. However, an analysis of HinfⅠ restriction site, a species-specific character between these two species, showed that the isolate did not match to either M. javanica or M. incognita.
전편의 실험적 연구에 이어서, 기 수행된 4개의 외부 접합부 시험체에 현존하는 여러 강도 예측식을 사용하여 콘크리트 기둥-강재 보 접합부의 내진 성능을 결정하는 패널 전단 및 지압 강도를 평가하였다. 또한, 접합부 패널지역의 변형특성을 묘사할 수 있는 일련의 스프링을 사용한 macro 형태의 해석모델이 논의되었으며, 이에 따라 Drain-2DX 및 IDARC 등의 상용프로그램을 사용하여 접합부의 패널전단 및 지압 파괴형태의 변형을 포함하는 단순해석이 수행되었다. 강도 예측결과에 의하면 본 연구에서 제시하는 수정된 내부 콘크리트 패널 전단 강도식을 포함하고 있는 ASCE 방법이 실험결과에 가장 근접한 것으로 나타났으며, 본 연구에서 검토된 패널지역 변형을 고려한 단순해석모델은 향후 전체 건물해석에 사용할수 있는 것으로 판단되었다.
반복하중을 지지하는 4개의 2/3 크리 접합부 실험을 통하여 콘크리트 기둥 및 강재 보로 구성된 골조에 대한 외부 모멘트 접합부의 이력거동을 조사하였다. 주요 실험 변수는 접합부에 배치된 후프근의 수, 콘크리트만의 전단강도 발현응ㄹ 유도한 접합부 상세, 강재 보 플랜지 상, 하부에 스터드 형태의 전단키를 사용한 상세 등이다. 실험 시 관측된 균열양상, 파괴형상 및 다양한 계측결과에 근거하여 접합부 상세에 따른 각 시험체의 거동이 자세히 기술되었으며, 항복 후 보유강도, 강성저하 정도 및 에너지 소산능력 등이 분석되었다. 실험결과에 의하면, 이들 중 패널 및 인접 기둥 영역에 각각 2개의 후프근을 갖는 시험체 (CF3) 가 가장 우수한 이력응답을 나타냈으며, 이러한 형태의 접합부 상헤는 우리나와 같은 약진 지역에 적합할 것으로 판단되었다.
희토류(Rare Earth) 함량이 높은 TRU 생성물 중의 RE 원소를 감소시키기 위하여 RE 원소와 UCl3의 산화반응을 이용한 RE 제거 공정의 타당성을 HSC Chemistry 코드를 이용하여 검토하였다. 사용후핵연료에 포함된 TRU 원소 및 RE 원소의 조성 및 열역학적 자료를 검토하였으며, UCl3와의 산화 반응에 따른 평형 자료를 계산하여 공정 가능성을 검토하였다. 실제 파이로 프로세싱 처리를 가정한 물질수지로부터 TRU 생성물의 RE 함량이 다른 두 가지 경우에 대하여 RE 원소 제거율과 TRU 회수율을 평가하였다. TRU 생성물을 산화제인 UCl3와 반응시켰을 때 각 원소의 Gibbs free energy의 차이에 의한 선택적 산화 반응이 일어났다. 투입된 UCl3 양을 조절하여 TRU 회수율을 최대로 유지하면서도 RE 원소를 제거하여 최종생성물의 TRU/ RE 비를 증가시킬 수 있는 가능성을 계산 결과로 확인하였다. 본 연구의 결과들은 열역학적 평형 자료에 기반한 결과이므로 실제 공정에 적용하기에는 많은 차이점이 존재한다. 그러나 TRU 물질을 취급하기 어려운 환경에서 파이로프로세싱의 TRU 생성물을 고속로의 핵연료로 공급하기 위한 공정 설계에 중요한 자료로 활용될 것으로 기대된다.
In this study, rational prediction models for the effective compressive strengths of HSC corner and interior columns with intervening NSC slabs are developed. A structural analogy between HSC column-NSC slab joint and brick masonry is used to develop the prediction models. In addition, the aspect ratio of slab thickness to column dimension and the surrounding slab confinement effect are considered in the models. The proposed prediction model is verified by comparison with experimental results and various prediction expressions. As a result, with average test-to-predicted ratios of 1.00 for HSC corner columns and 1.09 for interior columns, the proposed equation provides superior predictions over all of the existing effective strength prediction approaches including KCI structural concrete design code(2012).
Reactive oxygen species(ROS)에 의한 산화적 손상은 냉동보존 과정과 체외 배양과정 중 세포 생존률 감소의 주된 요인 중 하나이며, 특히 줄기세포의 경우 냉동보존 후 쉽게 분화하거나 사멸하는 경향이 있음이 잘 알려져 있다. 따라서 본 연구는 체외 배양된 인간 조혈모 줄기세포의 냉동보존 시 선별된 항산화제를 처리하여 항산화제가 줄기세포의 생존 및 자동분화에 미치는 영향을 조사하고자 하였다. 해동 후 세포의 생존률은 -tocopherol