Vaccination of Brucella abortus recombinant protein DapB induces CD4+/CD8+ T cells differentiation during Brucella abortus infection in BALB/c mice

Tran Xuan Ngoc Huy, Ched Nicole Turbela Aguilar, Trang Thi Nguyen, Said Abdi Salad, Hu Jang Lee, Jin Hur, Dong-Kwan Lee, Suk Kim 한국예방수의학회 2023 예방수의학회지 Vol.47 No.3

Extensive research and testing continue to be conducted for the development of vaccines targeting zoonotic diseases such as brucellosis. In this study, the potential of the DapB as a recombinant protein vaccine to effectively combat Brucella abortus 544 infection in BALB/c mice was evaluated. Western blotting assay results showed that recombinant protein DapB reacted with Brucella-positive serum, indicating its potential immunoreactivity. In vivo results showed that the peripheral blood CD4+ and CD8+ T cell population significantly increased in the DapB-immunized mice group after the first, second and third blood collection, compared to the control group that received PBS. Additionally, at the fourth blood collection, an increase in CD4+ T cell activation was observed in three vaccination groups compared to PBS negative control group. These results indicate the potential of DapB in stimulating cellular immunity. Fourteen days after infection, the bacterial load in the spleen was evaluated. The reduction in bacterial replication in the spleen by both DapB and RB51 highlights their protective efficacy against Brucella infection. These findings contribute to the ongoing efforts in developing effective vaccines against brucellosis and provide valuable insights for further research in this field.

4-F-PCP, a Novel PCP Analog Ameliorates the Depressive-Like Behavior of Chronic Social Defeat Stress Mice via NMDA Receptor Antagonism

( Darlene Mae D. Ortiz ),( Mikyung Kim ),( Hyun Jun Lee ),( Chrislean Jun Botanas ),( Raly James Perez Custodio ),( Leandro Val Sayson ),( Nicole Bon Campomayor ),( Chaeyeon Lee ),( Yong Sup Lee ),( J 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.

Identification of a glucokinase that generates a major glucose phosphorylation activity in the cyanobacterium Synechocystis sp. PCC 6803.

Lee, Jung-Mi,Ryu, Jee-Youn,Kim, Hyong-Ha,Choi, Sang-Bong,de Marsac, Nicole Tandeau,Park, Youn-Il Korean Society for Molecular Biology 2005 Molecules and cells Vol.19 No.2

<P>In silico analysis of genome of the cyanobacterium Synechocystis sp. PCC 6803 identified two genes, slr0329 and sll0593, that might participate in glucose (Glc) phosphorylation (www.kazusa.or.jp/cyano). In order to determine the functions of these two genes, we generated deletion mutants, and analyzed their phenotypes and enzymatic activities. In the presence of 10 mM Glc, wild-type (WT) and slr0329 defective strain (M1) grew fast with increased respiratory activity and NADPH production, whereas the sll0593 deletion mutant (M2) failed to show any of the Glc responses. WT and M1 were not significantly different in their glucokinase activity, but M2 had 90% less activity. Therefore, we propose that Sll0593 plays a major role in the phosphorylation of glucose in Synechocystis cells.</P>

UBE2T: A Molecular Regulator for Cancer Stemness in Hepatocellular Carcinoma

( Nicole Pui-yu Ho ),( Terence Kin Wah Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Increasing evidence showed that cancer stem cells (CSCs) play a critical role in regulating the tumor relapse and therapeutic resistance of hepatocellular carcinoma (HCC). Given high molecular similarities between liver CSCs and normal liver stem cells, we have enriched the normal stem cell populations by establishing a mouse partial hepactectomy model order to identify critical molecules involved in regulation of liver CSCs. By comparing the expression profiles between the early regenerating liver and intact one, UBE2T was found to be highly upregulated. This, together with the data showing upregulation of UBE2T in enriched liver CSC populations, suggest the role of UBE2T on regulating liver CSCs. Methods: We evaluated the clinic-pathological relevance of UBE2T by qPCR, western blot and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of UBE2T in regulating liver CSCs. The protein binding partner of UBE2T was identified by mass spectrometry analysis. Results: By qPCR analysis, UBE2T mRNA overexpression is found in over 90% of HCC samples and is associated with aggressive tumor behavior and poorer patients’ survival. Overexpression of UBE2T protein level in HCC clinical samples was further confirmed by western blot and IHC analyses. Using lentiviral based knockdown approach, suppression of UBE2T inhibited liver CSC properties, including self-renewal, tumorigenicity, drug resistance and expression of liver CSC markers. Using orthotopic liver xenograft model, UBE2T suppression led to decrease in tumor burden as well as lung metastasis in vivo. Mechanistically, we found UBE2T interacts with E3 ligase Mule and regulates its expression via ubiquitation. Since we further found that UBE2T mediates liver CSC function through Mule-mediated β-catenin activation. Conclusions: We have uncovered a novel UBE2T mediated signaling cascade in regulation of liver CSCs. Developing a specific inhibitor targeting this pathway may be a novel approach for HCC treatment.

Interleukin-1 Receptor Kinase 1 Augments Cancer Stemness and Drug Resistance via AP-1/AKR1B10 Signaling Cascade in Hepatocellular Carcinoma

( Nicole Pui Yu Ho ),( Bowie Lik Ling Cheng ),( Irene Oi Lin Ng ),( Terence Kin Wah Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Frequent relapse and drug resistance may be attributed to the existence of tumor-initiating cells (T-ICs) in hepatocellular carcinoma (HCC). We investigated the functional role and clinical significance of Interleukin-receptor associated kinase 1 (IRAK1) in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against HCC. Methods: We evaluated the clinic-pathological relevance of IRAK1 in HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of IRAK1 in regulation of liver T-ICs and sorafenib resistance. Molecular pathways mediating the phenotypic alterations was identified through RNA sequencing analysis and functional rescue experiments. The combinatorial effect of IRAK1/4 inhibitor and sorafenib was tested in vivo. Results: From transcriptome sequencing, we identified IRAK1 in TLR/IRAK pathway to be significantly upregulated in HCC. IRAK1 overexpression in HCC was further confirmed at mRNA and protein levels, and correlated with larger tumor size. Interestingly, IRAK4, an upstream regulator of IRAK1, was also found to be consistently upregulated. Through lentiviral based knockdown and overexpression approaches, we demonstrated that IRAK1 regulates traits of liver T-ICs. Similar phenotypic effects were observed when HCC cells were treated with IRAK1/4 inhibitor. Through RNA sequencing analysis by comparing expression profiles between sh-IRAK1 and control cells, we identified Aldo-Keto Reductase Family 1, Member 10 (AKR1B10) as a downstream target of IRAK1. AKR1B10 was found to be overexpressed in HCC, and correlated with IRAK1 expression. Functional analysis demonstrated that knockdown of AKR1B10 offset the IRAK1 induced T-IC functions through regulating AP-1 complex. Using HCC xenograft model, we found that IRAK1/4 inhibitor in combination with sorafenib demonstrated a maximal tumor suppressive effect. Conclusions: IRAK1/AP-1/AKR1B10 signaling cascade regulates liver T-ICs and sorafenib sensitivity. Targeting IRAK1 alone or in combination with sorafenib might be a novel strategy against HCC.

UBE2T: A Molecular Regulator for Cancer Stemness in Hepatocellular Carcinoma

( Nicole Pui-yu Ho ),( Terence Kin Wah Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Increasing evidence showed that cancer stem cells (CSCs) play a critical role in regulating the tumor relapse and therapeutic resistance of hepatocellular carcinoma (HCC). Given high molecular similarities between liver CSCs and normal liver stem cells, we have enriched the normal stem cell populations by establishing a mouse partial hepactectomy model order to identify critical molecules involved in regulation of liver CSCs. By comparing the expression profiles between the early regenerating liver and intact one, UBE2T was found to be highly upregulated. This, together with the data showing upregulation of UBE2T in enriched liver CSC populations, suggest the role of UBE2T on regulating liver CSCs. Methods: We evaluated the clinic-pathological relevance of UBE2T by qPCR, western blot and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of UBE2T in regulating liver CSCs. The protein binding partner of UBE2T was identified by mass spectrometry analysis. Results: By qPCR analysis, UBE2T mRNA overexpression is found in over 90% of HCC samples and is associated with aggressive tumor behavior and poorer patients’ survival. Overexpression of UBE2T protein level in HCC clinical samples was further confirmed by western blot and IHC analyses. Using lentiviral based knockdown approach, suppression of UBE2T inhibited liver CSC properties, including self-renewal, tumorigenicity, drug resistance and expression of liver CSC markers. Using orthotopic liver xenograft model, UBE2T suppression led to decrease in tumor burden as well as lung metastasis in vivo. Mechanistically, we found UBE2T interacts with E3 ligase Mule and regulates its expression via ubiquitation. Since we further found that UBE2T mediates liver CSC function through Mule-mediated β-catenin activation. Conclusions: We have uncovered a novel UBE2T mediated signaling cascade in regulation of liver CSCs. Developing a specific inhibitor targeting this pathway may be a novel approach for HCC treatment.

Comparison of mesenchymal-like stem/progenitor cells derived from supernumerary teeth with stem cells from human exfoliated deciduous teeth.

Lee, Sunray,An, Soyoun,Kang, Tae Hoon,Kim, Kyung Hye,Chang, Nicole Hyesoo,Kang, Seongman,Kwak, Chang Kon,Park, Hyun-Sook Future Medicine 2011 Regenerative medicine Vol.6 No.6

<P>Dental tissue has been the focus of attention as an easily accessible postnatal tissue source of high-quality stem cells. Since the first report on the dental pulp stem cells (DPSCs) from permanent third molar teeth, stem cells from human exfoliated deciduous teeth (SHED) were identified as a population distinct from DPSCs. In this study, we compared DPSCs from supernumerary teeth and SHED in three age- and sex-matched patients.</P>

Treatment and outcomes in undifferentiated and dedifferentiated endometrial carcinoma

Sarah Nicole Hamilton,Anna V. Tinker,Janice Kwon,Peter Lim,Iwa Kong,Sona Sihra,Martin Koebel,Cheng Han Lee 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.3

Objective: Undifferentiated and dedifferentiated endometrial carcinoma is a rare type of uterine malignancy. This study assesses disease characteristics, treatment and survival outcomes in patients with undifferentiated and dedifferentiated endometrial carcinoma treated at BC Cancer. Methods: All patients diagnosed with undifferentiated and dedifferentiated endometrial carcinoma between 2000 and 2019 at BC Cancer were reviewed centrally. Clinical, pathologic, treatment and outcomes were reviewed retrospectively. The Kaplan-Meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Multivariable analysis was performed using Cox regression analysis. Results: Fifty-two patients were included, 33% had undifferentiated carcinoma and 67% dedifferentiated carcinoma. Sixty-nine percent of those who had mismatch repair (MMR) testing of their tumor had an abnormal profile. The 5-year DFS was 80% (95% confidence interval [CI]=71%–89%) for stage I/II, 29% (95% CI=28%–40%) for stage III and 10% (95% CI 1%–19%) for stage IV. The 5-year OS was 84% (95% CI=75%–92%) for stage I/II, 38% (95% CI=26%–50%) for stage III and 12% (95% CI=1%–24%) for stage IV. Multivariate analysis showed that receiving adjuvant chemotherapy, adjuvant radiotherapy, lower stage and better Eastern Cooperative Group performance status were associated with improved DFS (p<0.05). Conclusion: Patients with stage I/II undifferentiated and dedifferentiated endometrial carcinoma had excellent survival outcomes, those with stage III/IV had worse outcomes, similar to previously reported. Adjuvant chemotherapy and radiotherapy were associated with improved DFS. MMR testing should be performed for these patients due to the high incidence of abnormal profiles.

망간(II)을 함유한 황산용액에서 Pb-Ag 양극의 산화반응

이만승,Lee, Man-Seung,Nicol, M.J. The Korean Institute of Resources Recycling 2017 資源 리싸이클링 Vol.26 No.4

황산용액에 함유된 망간(II)의 농도가 Pb-Ag양극의 산화거동에 미치는 영향을 1.8에서 2.0 V의 범위에서 정전위법으로 조사하였다. 산화전위가 높고 망간의 초기 농도가 낮은 조건에서는 망간(III)의 농도가 높았으며, 산화반응 후 용액을 분광학적으로 분석하여 이를 확인하였다. 1.8과 1.9 V에서는 $MnO_2$가 망간(II)의 산화에 의해 생성되나, 2.0 V에서는 망간(III)의 불균등화반응에 의해 형성되었다. 1.8 V에서 용액에 망간(II)이 존재하면 정전위조건에서 산화시킬 때 납이 $PbO_2$로 산화되지 않았다. 그러나 1.9와 2.0 V에서는 망간(II)농도가 증가함에 따라 $PbO_2$가 망간(II)에 의해 화학적으로 환원되어 $PbO_2$의 양이 감소하였다. The effect of Mn(II) concentration on the anodic reactions occurring on a Pb-Ag electrode in sulfuric acid solutions has been studied by potentiostatic oxidation in the potential range of 1.8 to 2.0 V. High oxidation potentials and low initial concentrations of Mn(II) resulted in higher concentrations of soluble Mn(III) ions which were obtained from spectrophotometric analysis of the solution after oxidation. $MnO_2$ was deposited on the electrode by electrochemical oxidation of Mn(II) at 1.8 and 1.9 V, while it was formed by disproportionation of Mn(III) at 2.0 V. No $PbO_2$ was formed in the presence of Mn(II) during potentiostatic oxidation treatment for two hours at 1.8 V. Chemical reduction of $PbO_2$ with Mn(II) led to a decrease in the amount of $PbO_2$ as Mn(II) concentration increased at 1.9 and 2.0 V.

Position Statements of the Emerging Trends Committee of the Asian Oceanian Society of Radiology on the Adoption and Implementation of Artificial Intelligence for Radiology

Wee Nicole Kessa,Git Kim-Ann,Lee Wen-Jeng,Raval Gaurang,Pattokhov Aziz,Ho Evelyn Lai Ming,Chuapetcharasopon Chamaree,Tomiyama Noriyuki,Ng Kwan Hoong,Tan Cher Heng 대한영상의학회 2024 Korean Journal of Radiology Vol.25 No.7

Artificial intelligence (AI) is rapidly gaining recognition in the radiology domain as a greater number of radiologists are becoming AI-literate. However, the adoption and implementation of AI solutions in clinical settings have been slow, with points of contention. A group of AI users comprising mainly clinical radiologists across various Asian countries, including India, Japan, Malaysia, Singapore, Taiwan, Thailand, and Uzbekistan, formed the working group. This study aimed to draft position statements regarding the application and clinical deployment of AI in radiology. The primary aim is to raise awareness among the general public, promote professional interest and discussion, clarify ethical considerations when implementing AI technology, and engage the radiology profession in the ever-changing clinical practice. These position statements highlight pertinent issues that need to be addressed between care providers and care recipients. More importantly, this will help legalize the use of non-human instruments in clinical deployment without compromising ethical considerations, decision-making precision, and clinical professional standards. We base our study on four main principles of medical care—respect for patient autonomy, beneficence, non-maleficence, and justice.