Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.

본 연구에서는 당동만을 중심으로 빈산소가 발생하는 물리적 해양환경 특성을 파악하고, 로지스틱 회귀분석을 이용해 빈 산소 발생확률을 예측하였다. 관측 자료를 분석한 결과, 브런트-바이살라 주파수는 수심이 깊은 만 입구보다 수심이 얕은 만 내측에서 더 크게 나타났다. 이는 당동만 내측에서 담수 유입으로 인해 표층 염분이 낮아져 강한 밀도 성층이 형성되었기 때문이다. 시간적으로 는 6월 ~ 9월까지 리차드슨 수와 브런트 바이살라 주파수가 매우 높게 나타났고, 9월 2일 이후로는 성층이 완화되어 감소하는 경향을 보였다. 당동만에서 관측된 용존산소 및 수온, 염분 자료를 분석한 결과, 저층의 용존산소 농도는 공통적으로 표층과 저층의 수온차에 가장 큰 영향을 받는 것으로 나타났다. 한편, 수심차(dz)를 고정된 변수로 두고, 수온차(dt)의 변화에 의한 빈산소의 발생 확률의 변화 를 계산한 결과, 수심차(dz)가 각각 5 m, 10 m, 15 m, 20 m일 경우, 수온차(dt)는 8℃, 7℃, 5℃, 3℃일 때 빈산소 발생확률이 70 %를 상회 하는 것으로 나타났다. 이는 당동만에서 수심차(dz)가 커질수록 빈산소 발생에 필요한 수온차(dt)는 작아지게 된다는 것을 뜻하며, 특 히 당동만에서 수심차(dz)가 20 m 내외인 지역은 빈산소가 발생하기 매우 쉬운 환경이라는 것을 알 수 있었다.

Hypoxia is one of the most common features of cancer. It is also associated with cancer progression and the acquisition of aggressiveness, which includes invasion and metastasis. Oral squamous cell carcinoma accounts for 90% of all oral cancers, and its 5-year survival rate is about 50%. Despite various attempts and trials, its prognosis has not improved. Among numerous adverse prognostic factors, hypoxia is suspected as one of the most important factors, as it increases the aggressiveness of oral cancer cells. We attempted to observe the effect of hypoxia on the expression of epithelial-mesenchymal transition markers in oral cancer cells. We analyzed and compared both the mRNA and protein expression levels of epithelial-mesenchymal markers using qRT-PCR and western blotting in both normoxic and hypoxic YD10B oral squamous cell carcinoma cells. Eighty-six genes were analyzed through real-time PCR using commercial microarray plates, performed in triplicate. Among the 86 genes, the expression of 24 were increased (≥ 2 fold) by hypoxia, while that of three genes was decreased (≥ 2 fold). Hypoxia significantly affects epithelial-mesenchymal transition-related genes. Further studies on the regulation of these genes may help to develop more efficient therapeutic modalities for oral cancer and to improve prognosis of oral cancer patients.

Chronic hypoxia is a major cause that increases neonatal mortality in the perinatal period. Vascular endothelial growth factor (VEGF) and its receptors induced by hypoxia are increased blood vessel permeability in the developing central nervous system and characterized as a critical factor in angiogenesis and vasculogenesis. This study investigated the development of the rat cerebellum with expression of VEGF and its receptors under chronic hypoxia in compare with normoxia. In addition, this study can contribute to the understanding of the effect development in the postnatal cerebellum. Rat pups were divided into two groups, normoxia and hypoxia group. The cerebellum of 35-day-old rat was removed and prepared for immunofluorescent staining. After staining, the sections were observed under the fluorescent microscope and were taken the picture using the microscopic-digital camera system. Expression of VEGF and Flk-1 restricted only to Purkinje cells, but feline sarcoma virus-like tyrosine kinase-1 (Flt-1) did not express in all of cerebellar layers. Under chronic hypoxia, expression of VEGF and fetal liver kinase-1 (Flk-1) increased in Purkinje cells but no changes in case of Flt-1. These results suggest that the source of VEGF and Flk-1 is Purkinje cells in the cerebellum. And increase of VEGF and Flk-1 expression in the murine cerebellum results from adaptive responses to chronic hypoxia.

본 연구에서는 2010년 여름에 천수만에서 저층해수를 채집하여 용존산소와 영양염 농도를 측정하였다. 또한 benthic chamber내의 해수시료를 시계열로 채집하는 자동화된 Benthic Lander를 설치하여 해수-퇴적물간 영양염 플럭스를 측정하였다. 오염된 인공호수 유출수가 들어오는 천수만 북쪽에서는 저층수의 용존산소는 2 mg/l로 hypoxia의 존재 가능성이 확인되었다. 반면 남쪽 천수만 입구의 저층 용존산소는 5 mg/l이었다. 영양염은 용존산소와 반대의 분포 경향을 보였고, N/P ratio의 변화는 hypoxia에 의해 발생된 인산염의 탈착과 용출 때문으로 보인다. 만 북쪽 해역의 유기탄소 산화율과 산소소비율은 남쪽 만 입구 해역보다 약 2배 큰 값을 보였고, 영양염 benthic flux는 천수만 북쪽에서 4내지 6배 높았다. 이러한 결과는 해수-퇴적물간 물질 플럭스를 정확히 추정하기 위해서는 hypoxia의 역할에 대한 이해가 중요하다는 점을 시사해준다.

Dental pulp is a highly vascularized tissue with high regenerative potential. Revascularization of severed vasculature in the tooth is required for pulp healing during avulsed tooth treatment. In this study, the relative expression of angiogenesis-related proteins was determined in human dental pulp cells using a human angiogenesis proteome profiler array. The proteome profiler array detected differentially expressed angiogenesis-related factors under conditions of hypoxia, which enhances the angiogenic potential of dental pulp cells. We confirmed that hypoxia regulates the mRNA expression of angiogenesis-related factors, including CXCL16 in dental pulp cells. Furthermore, conditioned media of hypoxic pulp cells induced tube-like structures of vascular endothelial cells, which were reduced by the neutralization of CXCL16 function. In conclusion, our data show that angiogenesisrelated factors are differentially expressed by hypoxia in dental pulp cells and suggest that CXCL16 may involve in the revascularization of hypoxic dental pulp.

본 연구는 소형화된 홀 소자를 이용하여 국내 패류 양식 생물 중 가장 많은 생산량을 보이는 참 굴(Crassostrea gigas)의 패각운동을 기초로, 연안역에서 빈산소에 대한 생물모니터링 시스템의 적 용 가능성을 조사하였다. 정상상태 패각운동의 측정을 위해서 여과해수에서 측정한 결과, 참굴 개 체는 평균 5~12 mm 정도의 개각상태를 유지하였으며, 패각운동 시 비교적 빠른 폐각상태를 보 였다가 느린 속도의 개각상태의 운동이 관찰되었다. 하지만, 주 · 야간 사이에는 큰 차이가 없었다 (p <0.05). 용존산소 농도를 7 mg l-1에서 3 mg l-1까지 감소시키면, 패각운동의 횟수는 증가를 나 타내었으며, 파형도 정상상태와 다르게 불안정한 파형을 보였다. 또한 용존산소가 2 mg l-1로 감 소된 후에는 패각운동의 크기가 점차 작아지거나, 폐각상태를 지시하는 파형이 관찰되었다. 이와 같은 생물모니터링 시스템을 패류 양식에 활용하여 빈산소와 같은 해양환경의 이상변동을 신속히 감지할 수 있다면, 어업피해를 감소시킬 수 있을 것으로 기대된다.

Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived essential factor for osteoclastogenesis. During endochondral bone formation, hypertrophic chondrocytes calcify cartilage matrix that is subsequently resorbed by osteoclasts in order to be replaced by new bone. Hypoxia-induced upregulation of RANKL expression has been previously demonstrated in an in vitro system using osteoblasts; however, the involved mechanism remains unclear in chondrocytes. In the present study, we investigated whether hypoxia regulates RANKL expression in ATDC5 cells, a murine chondrogenic cell line, and hypoxiainducible factor-1α (HIF-1α) mediates hypoxia-induced RANKL expression by transactivating the RANKL promoter. The expression levels of RANKL mRNA and protein, as well as HIF-1α protein, were significantly increased in ATDC5 cells under hypoxic condition. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression under normoxic conditions, whereas dominant negative HIF-1α reduced hypoxia-induced RANKL expression. HIF-1α increased RANKL promoter reporter activity in a HIF-1α binding element-dependent manner in ATDC5 cells. Hypoxia-induced RANKL levels were much higher in differentiated ATDC5 cells, as compared to proliferating ATDC5 cells. These results suggested that under hypoxic conditions, HIF-1α mediates induction of RANKL expression in chondrocytes; in addition, hypoxia plays a role in osteoclastogenesis during endochondral bone formation, at least in part, through the induction of RANKL expression in hypertrophic chondrocytes.

The objective of this study was to evaluate the effects of acute hypoxia on the physiological stress responses (plasma cortisol as the primary response, and hematocrit, hemoglobin, plasma glucose, sodium, chloride, osmolality, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as the secondary responses) of Korean rockfish. The mortality in Korean rockfish started at 0.7 mg L-1 and 0.8 mg L-1 levels at 12℃ and 20℃, respectively. And the time required for the mortality in experimental fish was 274 and 148 minutes at 12℃ and 20℃, respectively. Levels of hematocrit, hemoglobin, AST, ALT, ion concentration, osmolality, glucose and cortisol had significantly increased with decreasing dissolved oxygen at 12℃ and 20℃.

Osteocytes may function as mechanotransducers by regulating local osteoclastogenesis. Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. The hypoxia induced osteoclastogenesis via increased RANKL expression in osteoblasts was demonstrated. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. In the present study, we investigated whether hypoxia regulates RANKL expression in murine osteocytes and HIF-1α mediates hypoxia-induced RANKL expression by transactivating RANKL promoter, to elucidate the role of osteocyte in osteoclastogenesis in the context of hypoxic condition. The expression levels of RANKL mRNA and protein, as well as hypoxia inducible factor-1α (HIF-1α) protein, were significantly increased in hypoxic condition in MLO-Y4s. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression in MLO-Y4s under normoxic conditions, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL expression. To further explore to find if HIF-1α directly regulates RANKL transcription, a luciferase reporter assay was conducted. Hypoxia significantly increased RANKL promoter activity, whereas mutations of putative HIF-1α binding elements in RANKL promoter prevented this hypoxia-induced RANKL promoter activity in MLO-Y4s. These results suggest that HIF-1α mediates hypoxia-induced up-regulation of RANKL expression, and that in osteocytes of mechanically unloaded bone, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in osteocytes.

본 연구는 반폐쇄성 해역인 마산만을 대상으로 eco-hydrodynamic model을 이용하여 해역의 물리적 구조를 분석하여, 물리적 안정도를 나타내는 수직확산계수를 산정하고, 생태계 모델에 적용하여 그 타당성을 평가하는 것이다. 해역의 물리적 구조는 EFDC모델을 사용하여 구하였으며, 수직 확산계수는 수층간의 밀도차이가 커질수록 감소하도록 산정하였다. 산정된 수직 확산계수를 Stella프로그램을 이용하여 구축한 생태계모델에 적용하여, 용존산소 재현성으로 그 타당성을 평가하였다. 수직확산계수 변화를 추정하여 적용한 모델의 결과는 2008년의 R2값은 0.529~0.700으로 나타났으며, 2009년 R2값은 0.542~0.791로 나타났다. 계산값은 관측값과 유사한 경향을 나타내었으며, 만 내측의 빈산소수괴를 잘 재현하였다. 본 연구에서 적용된 수직확산계수는 해역의 밀도성층과 물리적 안정도를 의미하는데, 향후 폐쇄성 내만해역의 빈산소수괴 발생 예측에 유용하게 활용될 것으로 판단된다.