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Combination of sorafenib and sodium diethylthiocarbamate synergistically induce cell death in hepatitis B virus derived liver cancer via suppression of the PI3K/Akt/mTOR pathway
No full text목적: 본 연구는 디설피람 유도체인 DDC (sodium diethyldithiocarbamate)를 소라페닙과 조합하여 B형간염 유래 간암세포에서의 항암 작용 가능성을 확인하고자 하였다.
대상 및 방법: 간암 조직과 세포주에서 실시간 폴리머아제 연쇄반응(qRT-PCR)과 면역블롯팅(immunoblotting)을 사용하여 초과산화이온1 (SOD1)과 B형간염 바이러스 단백질(HBx)의 발현 수준을 확인하였다. B형간염 양성 간암세포와 B형간염 음성 간암 세포에서 PI3K/Akt/mTOR 경로를 비교하였다. 소라페닙과 DDC 조합요법에서 세포 생존율, 활성산소 수준 및 세포자멸사 지표들을 평가했고, 소라페닙과 DDC 의 경구 공급과 관련하여 이종이식 생체 내 실험을 수행하였다.
결과: 환자 조직 검체와 B형간염 양성 세포에서 HBx와 SOD1의 발현이 증가되어 있었으며 둘 사이에 유의한 상관관계가 있었다. DDC 치료는 HepG2.2.15 세포에서 SOD1과 HBx의 발현을 효과적으로 감소시켰다. DDC와 소라페닙의 조합요법은 HBx의 발현을 감소시켰다. 소라페닙은 B형간염 양성 세포에서 PI3K/Akt/mTOR 경로를 억제하였으며, 이는 DDC에 의해 더 강화되어 암세포 생존율을 감소시켰다. 그러나 세포자멸사 지표들의 유의한 증가를 보이지는 않았다. 이종이식 생체 내 실험에서 소라페닙과 DDC 조합요법의 경구 투약은 종양의 성장을 억제하였다.
결론: DDC와 소라페닙의 조합요법은 B형간염 유래 간암세포에서 SOD1과 PI3K/Akt/mTOR 경로에 효과적으로 작용한다. 이 조합요법은 SOD1의 발현을 감소시키고, 산화 스트레스를 유도하며, 세포 생존율을 억제함으로써 B형간염 유래 간암세포의 치료에 효과적인 전략이 될 수 있다.|Background/Aims: This study explored the anti-cancer potential of combining sodium diethyldithiocarbamate (DDC), a disulfiram derivative, with sorafenib in HBV-positive liver cancer cells.
Methods: We assessed the expression levels of SOD1 and HBx using qRT-PCR and immunoblotting in liver cancer samples and cell lines. The PI3K/Akt/mTOR pathway was compared between HBV-positive and HBV-negative liver cancer cells. Cell viability, levels of reactive oxygen species, and apoptotic markers were examined in response to sorafenib and DDC combination treatment. Furthermore, we conducted an in vivo xenograft experiment involving oral gavage of sorafenib and DDC.
Results: Patient tissue samples and cells that were positive for HBV showed increased expressions of HBx and SOD1, with a significant correlation between the two. DDC treatment effectively reduced the expression of SOD1 and HBx in HepG2.2.15 cells. When combined, DDC and sorafenib synergistically decreased the expression of HBx. Sorafenib inhibited the PI3K/Akt/mTOR pathway in HBV-positive cells, and this inhibition was further enhanced by DDC, leading to decrease in cancer cell viability. However, the apoptotic markers did not show a significant increase. In an in vivo xenograft model, the combined oral administration of sorafenib and DDC synergistically inhibited tumor growth.
Conclusions: The combination of DDC and sorafenib effectively targets SOD1 and the PI3K/Akt/mTOR pathway in HBV-positive liver cancers. By reducing SOD1 expression, inducing oxidative stress, and suppressing cell viability, this combination therapy presents a promising strategy for the treatment of HBV-related liver cancers.Docto
Mediating Effect of Firefighters' Resilience and Public Service Motivation Regarding the Influence of Depression on Their Work Engagement During COVID-19
No full textIn this study, we aimed to investigate the influence of resilience or public service motivation (PSM) on firefighters' work engagement during the coronavirus disease (COVID-19) pandemic. We conducted an online survey with 304 firefighters assigned to Gyeonggi-do between October 27 and 28, 2022, and collected their demographic information; work-related data; mood, anxiety and insomnia symptoms; and work-related attitudes. The leading causes of firefighters' stress were physical and mental health decline due to heavy workloads (46.4%), verbal abuse and assault from civilians (33.9%), conflict with coworkers (18.4%), and death of colleagues (13.2%). The results of the logistic regression analysis revealed that high levels of resilience (OR = 1.28, p < 0.001), service motivation (OR = 1.17, p < 0.001), and non-exposure to death (OR = 0.33, p = 0.005) led to high work engagement. Mediation analysis showed that resilience and PSM mediated the influence of depression on work engagement. The work engagement of firefighters is influenced by resilience, PSM, and exposure to death
Surgical outcomes including visual improvement after glaucoma surgery in patients with neovascular glaucoma
No full textPurpose: This study aimed to evaluate the prognostic factors affecting surgical outcomes, including visual acuity (VA) improvement, after glaucoma surgery in patients with neovascular glaucoma (NVG).
Methods: The medical records of 116 patients (116 eyes) with NVG who had undergone trabeculectomy or Ahmed glaucoma valve implantation were reviewed retrospectively. The primary outcome measure was surgical success at 6 postoperative months, defined as sufficient intraocular pressure (IOP) reduction (IOP ≤21 mmHg, ≥20% reduction, regardless of topical medication use) without additional glaucoma surgery, hypotony, or progression to no light perception. Success was categorized as complete or qualified based on whether an improvement in VA was observed in addition to the abovementioned definition.
Results: The complete and qualified success rates at 6 months were 44.6% and 92.2%, respectively. Age (p = 0.001), preoperative best-corrected VA (p = 0.031), duration of decreased VA (p = 0.001), closed-angle status (p = 0.013), and etiology (p = 0.007) differed significantly between the groups with and without complete success. Multivariate analysis revealed that age (odds ratio [OR] 1.05; p = 0.026), duration of decreased VA (OR 1.05; p = 0.016), and 360° closed-angle status (OR 3.27; p = 0.031) were risk factors for surgical failure according to the complete success criteria, but not the qualified success criteria.
Conclusions: Patients with NVG showed improved visual prognosis and successful IOP reduction after glaucoma surgery at a relatively younger age if the duration of visual loss was not prolonged and the angle status was not completely closed
Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer
No full textPurpose: We explored the efficacy of PARP inhibition with or without programmed death ligand-1 (PD-L1) blockade as chemotherapy-free maintenance therapy for advanced triple-negative breast cancer (aTNBC) sensitive to platinum-based chemotherapy.
Patients and methods: In the phase II non-comparative DORA trial (NCT03167619), patients with ongoing stable disease (SD) or complete/partial response (CR/PR) to first- or second-line platinum-based chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1,500 mg on day 1 every 4 weeks. The primary objective was to compare progression-free survival (PFS) versus a historical control of continued platinum-based therapy.
Results: 45 patients were randomized (23 to olaparib alone, 22 to the combination; 3 with estrogen/progesterone receptor expression 1%-10%). At 9.8 months' median follow-up, median PFS from randomization was 4.0 [95% confidence interval (CI), 2.6-6.1] months with olaparib and 6.1 (95% CI, 3.7-10.1) months with the combination, both significantly longer than the historical control (P = 0.0023 and P < 0.0001, respectively). Clinical benefit rates (SD ≥24 weeks or CR/PR) were 44% (95% CI, 23%-66%) and 36% (95% CI, 17%-59%) in the monotherapy and combination arms, respectively. Sustained clinical benefit was seen irrespective of germline BRCA mutation or PD-L1 status, but tended to be associated with CR/PR to prior platinum, particularly in the olaparib-alone arm. No new safety signals were reported.
Conclusions: PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance
Influence of the Morphology of Li2S on the Electrochemical Performance of Li6PS5Cl
No full text전고체전지는 차세대 전지 중 하나로, 액체전해질을 고체전해질로 대체한 전지이며, 액체전해질이 갖는 위험성을 해결하고 보다 높은 에너지밀도를 실현할 수 있는 전지이다. 황화물계 고체전해질은 무른 물성과 높은 이온전도성으로 인해 많은 관심을 받고 있으나, 고체전해질을 상용화하기 위해서는 제조 공정이나 출발 물질의 가격이 낮아질 필요가 있 다. 이 연구는 Li6PS5Cl의 출발 물질 중 하나인 Li2S를 대상으로 하며, 서로 다른 공급업체의 Li2S를 바탕으로 물질 분석과 이를 바탕으로 합성한 Li6PS5Cl의 합성 여부와 물질 분석 및 전기화학적 성능을 비교한다.
All- solid-state batteries, as one of the next-generation battery technologies, replace liquid electrolytes with solid ones, mitigating the safety concerns associated with liquid electrolytes and enabling higher energy density. Sulfide-based solid electrolytes, due to their soft mechanical properties and high ionic conductivity, have garnered significant interest. However, for the commercialization of solid-state electrolytes, there is a need to reduce manufacturing costs and the price of starting materials. This study deals with Li2S, one of the starting materials, and compares the electrochemical performance of Li6PS5Cl synthesized based on material analysis using Li2S from different suppliers
Spatiotemporal tracking of intracellular nanoparticles using complementary imaging systems reveals acute ferroptosis triggered by burst reduction of ferric ions
No full textUptake and intracellular trafficking of nanoparticles are tightly regulated by their interactions with cellular organelles and physiological microenvironment. Although the dynamic physicochemical reactions at the interface of nanoparticles and cells ultimately determine the intracellular distribution and fate, microscopic tracing and quantitative analysis of the nanoparticles have been hampered by the limited resolution associated with individual nanoparticle trafficking. Herein, we report spatiotemporal investigations on autophagic clearance of biodegradable iron oxide-silica core-shell nanoparticles in terms of intracellular trafficking and ionic dissolution at a single cell level using multimodal imaging systems. By combining transmission electron microscopy and super-resolution confocal laser scanning microscopy with fluorescence correlation spectroscopy, the complementary imaging analysis exclusively shows the intracellular uptake, endosomal fusion and biodegradative clearance, leading to identify the step-by-step endocytic transport pathway and autophagic degradation pathways. Tracing the intracellular trafficking of nanoparticles reveals that they are spontaneously transported from endosomes to lysosomes, and transiently stimulate autophagy while maintaining cell viability. While protecting iron oxide core, the silica shell is gradually degraded during endocytosis and autophagic clearance, resulting in ionic dissolution of iron oxide in acidic environment. Moreover, burst reduction of ferric ions by adding ascorbic acid readily triggers acute ferroptosis owing to rapid supplement of ferrous ions and Fenton reaction in cancer cells. The complementary imaging strategy provides insights into the design of biocompatible nanomedicines for cellular delivery and the degradative mechanisms beyond the intracellular fate
A study on the characteristics of clinical subtyps in patients with psoriasis
No full text연구배경 및 목적: 건선은 유전과 환경이 복합적으로 작용하여 발생하는 면역 매개성 만성, 재발 성, 염증성, 전신성 질환이다. 건선의 병인은 유전, 면역, 환경 등 여러 요소를 포함한다. 이러한 요소의 차이로 인해 건선은 형태, 분포, 중증도에 있어서 개인 간의 큰 차이가 있으며, 본 연구는 실제 임상에서 관찰된 건선 환자의 인구통계학적 정보, 건선 병변의 분포와 중증도, 건선 관절염, 손발톱 변형, 동반 질환 등의 특성을 수집하여 농포성 건선을 포함한 건선의 아형별 환자의 특성 을 분석하여 질병에 대한 이해를 높이고 질병을 더 잘 관리하는 것을 목적으로 한다. 또한 건선 의 발병 기전에서 IL-23의 중요한 역할을 고려하여 4명의 연구 환자의 혈액을 채취하여 IL-23의 유전적 변이와 건선의 발병기전의 연관성을 탐색하고자 한다.
연구방법: 2021년 10월부터 2022년 2월까지 서울아산병원 피부과에 방문한 조직학적으로 진단된 건선 환자 30명의 의무기록을 후향적으로 분석하였다. 그 중에서 4명 환자의 혈액 샘플을 채취하 여 혈액 세포에서 RNA와 유전체 DNA를 분리하였다. 이후 PCR을 이용하여 염증성 사이토카인 IL-23의 유전자를 증폭한 후, 분리된 RNA 또는 유전체 DNA의 PCR 산물을 sequencing하여 건선 환자 특이적 돌연변이의 존재 여부를 확인하였다.
연구결과: 포함된 건선 환자의 평균연령은 44.5세였으며 남성이 여성에 비해 1.3배 많았다. 남성 과 여성을 비교하였을 때 남성의 PASI (Psoriasis Area and Severity Index) 점수는 여성보다 높았고 (남 PASI 21 vs 여 PASI 16), BMI＞25(남75% vs 여25%)、고혈압 동반율 (남50% vs 여0%) 여성보 다 높게 나왔다. 조기 발병군과 후기 발병군 건선환자를 비교하였을 때 후기 발병군에 남성이 87.5%으로 압도적인 비율을 차지하였고 건선 관절염(조기 발병13.6% vs 후기 발병 37.5%), 당뇨 (초기 발병0% vs 후기발병 25%), 고혈압(초기 발병22.7% vs 후기 발병 62.5%)의 비율은 후기 발 병군에서 조기 발병군보다 높았다. 한편, 손발바닥에 병변이 있는 환자 (P<0.001) 및 항-TNF치료 제 치료 받은 환자 (P=0.001) 의 비율은 농포성 건선군에서 통계적으로 유의미하게 높았다. 가족 력, 중증도, 농포성, 만기 발병 4가지 특징을 가진 건선 환자에서 유전자 돌연변이를 확인하지 못 했 하였다.
결론: 본 연구에서는 성별에 따라 건선의 임상 양상이 달라지는 것을 발견하였다. 남성 건선 환자 는 더 심한 건선 중증도, 높은 비만도를 가지고 동반질환을 동반하는 비율도 여성에 비해 높은 것으로 나와 보다 더 면밀한 관찰과 치료가 필요하다. 또한 삼차 병원으로 내원한 농포성 건선은 TNF 억제제 사용과 유의한 상관관계가 있는 것으로 나왔다. 마지막으로 건선의 특정 임상 양상과 IL23 변이와의 연관성은 발견하지 못하였다.
중심어: Psoriasis，Real world, Retrospective studies, Psoriasis Area Severity IndexBlood sample, Cytokines, IL-23Maste
Highly Permeable Mixed Matrix Membranes for Gas Separation via Dual Defect-Engineered Zeolitic Imidazolate Framework-8
No full textDefect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH3COO)2·2H2O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m2 g-1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C2H4) permeability (281 Barrer) with a moderate ethylene/ethane (C2H4/C2H6) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C2H4/C2H6 separation
Techno-economic Analysis and Life Cycle Impact Assessment for the Valorisation of Kraft Lignin and Low-Voltage Hydrogen Production
No full textThis study presents a comparative techno-economic analysis and life cycle impact assessment of hydrogen production from the kraft lignin depolymerization (KLD) with those produced from alkaline electrolysis cell (AEC) and proton exchange membrane electrolysis (PEM). This process happens in a continuous modular flow reactor by using the phosphomolybdic acid as a redox-active catalyst and includes depolymerizing the kraft lignin, producing vanillin, acetovanillone, and hydrogen under a low-voltage condition. For the techno-economic analysis, first, the processes were modelled by using the Aspen Plus V12.1 software and then the results were transferred to Aspen Process Economic Analyzer V12 for economic evaluation. In the next step, the life cycle impact assessment was proposed by using the openLCA V1.11.0 software along with the Environmental Footprint database (MID-Point indicator), and 18 impacts were investigated. According to the techno-economic analysis, KLD exhibits a total capital cost that surpasses that of AEC and PEM by more than 18% and 11%, respectively. Furthermore, KLD’s equipment cost exceeds that of AEC and PEM by approximately 0.5% and 7%, respectively, and necessitates additional components. On the other hand, the life cycle assessment revealed that KLD yields lesser environmental impacts than AEC, while PEM exhibits the most exemplary environmental performance
Corrosion behavior of laser welded AZ31 magnesium alloy
No full text최근 대두되는 환경 문제와 관련하여 자동차 산업분야에서도 연비 향상을 위해 경량 소재의 적용에 관심이 높아지고 있다. 마그네슘 합금의 고유 특성인 높은 비강도는 이러한 경량화에 적합한 특성으로 평가받지만, 빠르게 적용 범위를 늘려가고 있는 초고장력 강 또는 알루미늄 합금과 같은 경쟁소재 대비 내부식성, 성형성, 용접성 등에서 단점을 나타내어 제한적으로 적용되고 있다. 높은 경량화 효과를 얻을 수 있는 마그네슘 합금의 적용 범위를 확대하기 위한 연구의 일환으로 최근 내부식성을 개선한 신 합금이 개발되었으나, 해당 합금의 용접부에 대한 연구는 미미한 실정이다.
따라서 본 연구에서는 레이저 용접(Laser Beam Welding, LBW) 공정을 이용하여 AZ31 마그네슘 합금 및 Modified-AZ31 마그네슘 합금을 각각 동종 접합하였으며, 용접 전/후의 미세조직 비교를 위해 결정립 크기와 이차 금속간 화합물(이하 이차상)의 크기 및 분율을 정량화 하였다. 특히, 용접 전/후 이차상의 크기, 형태, 조성 등의 변화를 관찰함으로써 레이저 용접이 내부식성 개선의 주요 요소인 이차상에 미치는 영향을 중점적으로 분석하였다. 또한 염수 분무 시험과 침지시험을 실시하여 레이저 용접에 따른 부식 속도 변화를 관찰하였으며, 영역별 국소 부위(1mm Ø)에 대해 개방 회로 전위(Open Circuit Potential, OCP)와 동전위 분극 시험(Potentiodynamic polarization test)를 실시하여 두 합금의 영역별 전기화학적 부식 거동을 비교 분석하였다. 최종적으로 미세조직 변화와 부식 거동 변화를 연관 지어 해석함으로써, 레이저 용접부의 미세조직적 변화를 규명하고 부식 거동과의 상관관계를 고찰하였다.Maste