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马宜菲 ( Ma-yifei ),金明华 ( Jin-minghua ) 경상대학교 교육연구원 2023 현대교육연구 Vol.35 No.1
School bullying is a widespread and seriously harmful social problem that needs to be of great concern to the whole society. According to a UNESCO report, school violence and bullying are major problems worldwide. Formally speaking, school bullying is characterized by the low age of the subjects, the diversity of the methods, the violence, the repetitiveness of the behaviors, and the long-term nature, and the subjective maliciousness of the bully, the serious consequences of the bullying, and the serious social harm of the bullying behavior, and some serious bullying behaviors have certain criminal illegality, which cause great harm to the physical and psychological aspects of the bully. To address the phenomenon of school bullying, we should not only focus on the causes of school bullying, and look for the sources of school bullying from the perspectives of individuals, families, schools and society, but also find a reasonable means of regulation from legislation and judicial practice to maintain the peace of campus and society and protect the rights and interests of the bully. Although China currently has laws to protect the legal rights of minors, there are no specific provisions to regulate bullying in schools. In judicial practice, because of the young age of the group in which school bullying occurs, the punishment for bullying behavior is too light to achieve educational and preventive effects. Bullying in schools is also an important issue globally. In view of the laws and regulations on school bullying in foreign countries, some countries have already introduced specific laws and regulations on school bullying. Therefore, we should further improve the law on the protection of minors and other related laws and introduce relevant laws on school bullying as soon as possible to make up for the current problems of school bullying, taking into account the legislation and judicial practice. And through the cooperation of family, school and society, the legal awareness of minors should be enhanced to curb the phenomenon of school bullying from the source.
Hoang, Van-Hai,Tran, Phuong-Thao,Cui, Minghua,Ngo, Van T. H.,Ann, Jihyae,Park, Jongmi,Lee, Jiyoun,Choi, Kwanghyun,Cho, Hanyang,Kim, Hee,Ha, Hee-Jin,Hong, Hyun-Seok,Choi, Sun,Kim, Young-Ho,Lee, Jeewoo American Chemical Society 2017 Journal of medicinal chemistry Vol.60 No.6
<P>Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of beta-amyloid peptides (pGlu-A beta) and thus may participate in the pathogenesis of Alzheimer's disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, A beta 3E-42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform A beta and total A beta and restored cognitive functions. This potent A beta-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong-interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.</P>
Hoang, Van-Hai,Ngo, Van T. H.,Cui, Minghua,Manh, Nguyen Van,Tran, Phuong-Thao,Ann, Jihyae,Ha, Hee-Jin,Kim, Hee,Choi, Kwanghyun,Kim, Young-Ho,Chang, Hyerim,Macalino, Stephani Joy Y.,Lee, Jiyoun,Choi, S American Chemical Society 2019 Journal of medicinal chemistry Vol.62 No.17
<P>Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of β-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor <B>1</B>, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.</P> [FIG OMISSION]</BR>
Ngo, Van T.H.,Hoang, Van-Hai,Tran, Phuong-Thao,Van Manh, Nguyen,Ann, Jihyae,Kim, Eunhye,Cui, Minghua,Choi, Sun,Lee, Jiyoun,Kim, Hee,Ha, Hee-Jin,Choi, Kwanghyun,Kim, Young-Ho,Lee, Jeewoo Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.12
<P><B>Abstract</B></P> <P>Glutamyl cyclase (QC) is a promising therapeutic target because of its involvement in the pathogenesis of Alzheimer’s disease. In this study, we developed novel QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore. Several potent inhibitors were identified, showing IC<SUB>50</SUB> values in a low nanomolar range, and were further studied for <I>in vitro</I> toxicity and <I>in vivo</I> activity. Among these, inhibitors <B>51</B> and <B>53</B> displayed the most potent Aβ<SUB>N3pE−40</SUB>-lowering effects in <I>in vivo</I> acute model with reasonable BBB penetration, without showing cytotoxicity and <I>h</I>ERG inhibition. The molecular modeling analysis of <B>53</B> indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound <B>53</B> may serve as a potential candidate for anti-Alzheimer’s agents.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Ngo, Van T.H.,Hoang, Van-Hai,Tran, Phuong-Thao,Ann, Jihyae,Cui, Minghua,Park, Gyungseo,Choi, Sun,Lee, Jiyoun,Kim, Hee,Ha, Hee-Jin,Choi, Kwanghyun,Kim, Young-Ho,Lee, Jeewoo Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.5
<P><B>Abstract</B></P> <P>Pyroglutamate-modified amyloid β peptides (pGlu-Aβ) are highly neurotoxic and promote the formation of amyloid plaques. The pGlu-Aβ peptides are generated by glutaminyl cyclase (QC), and recent clinical studies indicate that QC represents an alternative therapeutic target to treat Alzheimer’s disease (AD). We have previously developed a series of QC inhibitors with an extended pharmacophoric scaffold, termed the Arg-mimetic D-region. In the present study, we focused on the structure activity relationship (SAR) of analogues with modifications in the D-region and evaluated their biological activity. Most compounds in this series exhibited potent activity in vitro, and our SAR analysis and the molecular docking studies identified compound <B>202</B> as a potential candidate because it forms an additional hydrophobic interaction in the <I>h</I>QC active site. Overall, our study provides valuable insights into the Arg-mimetic pharmacophore that will guide the design of novel QC inhibitors as potential treatments for AD.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation
Kim, Min Soo,Lee, Sangmin,Yun, Sanguk,Suh, Pann-Ghill,Park, Jongmi,Cui, Minghua,Choi, Sun,Cha, Sun-Shin,Jin, Wook Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.107 No.2
<P><B>Abstract</B></P> <P>The DJ-1 protein engages in diverse cellular and pathological processes, including tumorigenesis, apoptosis, sperm fertilization, and the progression of Parkinson’s disease (PD). The functional dimeric form of DJ-1 transforms into non-functional filamentous aggregates in an inorganic phosphate (P<SUB>i</SUB>)-dependent manner in vitro. Here, we demonstrated that P<SUB>i</SUB> and reactive oxygen species (ROS) induce DJ-1 aggregation in Neuro2A and SH-SY5Y cells. Remarkably, tartrate treatment significantly reduced P<SUB>i</SUB>- and ROS-induced DJ-1 aggregation and restored P<SUB>i</SUB>- and ROS-provoked cell death using quantitative data as mean±standard deviation, and statistics. Mechanistically, tartrate prevented DJ-1 aggregation via occupying the P<SUB>i</SUB>-binding site. These findings revealed an unexpected physiological role of tartrate in the maintenance of DJ-1 function, and thus, a potential use as an inhibitor of DJ-1 aggregation.</P>
Jeong, Chang-Bum,Kang, Hye-Min,Lee, Young Hwan,Kim, Min-Sub,Lee, Jin-Sol,Seo, Jung Soo,Wang, Minghua,Lee, Jae-Seong American Chemical Society 2018 Environmental science & technology Vol.52 No.19
<P>Among the various materials found inside microplastic pollution, nanosized microplastics are of particular concern due to difficulties in quantification and detection; moreover, they are predicted to be abundant in aquatic environments with stronger toxicity than microsized microplastics. Here, we demonstrated a stronger accumulation of nanosized microbeads in the marine rotifer <I>Brachionus koreanus</I> compared to microsized ones, which was associated with oxidative stress-induced damages on lipid membranes. In addition, multixenobiotic resistance conferred by <I>P</I>-glycoproteins and multidrug resistance proteins, as a first line of membrane defense, was inhibited by nanoplastic pre-exposure, leading to enhanced toxicity of 2,2′,4,4′-tetrabromodiphenyl ether and triclosan in <I>B. koreanus</I>. Our study provides a molecular mechanistic insight into the toxicity of nanosized microplastics toward aquatic invertebrates and further implies the significance of synergetic effects of microplastics with other environmental persistent organic pollutants.</P> [FIG OMISSION]</BR>
Fengnan Lian,Dan Wang,Shuo Yao,Lirui Ge,Yue Wang,Yuyi Zhao,Jinbin Zhao,Xiuling Song,Chao Zhao,Jinhua Li,Yajuan Liu,Minghua Jin,Kun Xu 한국식품과학회 2021 Food Science and Biotechnology Vol.30 No.8
This research aimed to detect Escherichia coli O157:H7 in milk based on immunomagnetic probe separation technology and quenching effect of gold nanoparticles to Rhodamine B. Streptavidin-modified magnetic beads (MBs) were combined with biotin-modified antibodies to capture E. coli O157:H7 specifically. Gold nanoparticle (AuNPs) was incubated with sulfhydryl-modified aptamers (SH-Aptamers) to obtain the Aptamers-AuNPs probe. After magnetic beads captured target bacteria and formed a sandwich structure with the gold nanoprobe, Rhodamine B was added into complex to obtain fluorescent signal changes. Our results demonstrated that the established method could detect E. coli O157:H7 in the range of 101–107 CFU/mL, and the limit of detection (LOD) was 0.35 CFU/mL in TBST buffer (pH = 7.4). In milk simulation samples, the LOD of this method was 1.03 CFU/mL. Our research provides a promising approach on the detection of E. coli O157:H7.
Kim, Hyoun Sook,Im, Ha Na,An, Doo Ri,Yoon, Ji Young,Jang, Jun Young,Mobashery, Shahriar,Hesek, Dusan,Lee, Mijoon,Yoo, Jakyung,Cui, Minghua,Choi, Sun,Kim, Cheolhee,Lee, Nam Ki,Kim, Soon-Jong,Kim, Jin Y American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.41
<▼1><P><B>Background:</B> Csd6 is one of the cell shape-determining proteins in <I>H. pylori</I>.</P><P><B>Results:</B> The active site of Csd6 is tailored to function as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase in the peptidoglycan-trimming process.</P><P><B>Conclusion:</B> Csd6 constitutes a new family of <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase.</P><P><B>Significance:</B> The substrate limitation of Csd6 is a strategy that <I>H. pylori</I> uses to regulate its helical cell shape and motility.</P></▼1><▼2><P><I>Helicobacter pylori</I> causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In <I>H. pylori</I>, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidases. Mass analyses confirm that Csd6 functions only as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase and not as an <SMALL>L</SMALL>,<SMALL>D</SMALL>-transpeptidase. The <SMALL>D</SMALL>-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and <I>in silico</I> docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that <I>H. pylori</I> Csd6 and its homologs constitute a new family of <SMALL>L</SMALL>,<SMALL>D</SMALL>-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of <I>H. pylori</I>.</P></▼2>