Cholinesterases inhibition studies of biological active compounds from the rhizomes of <i>Alpinia officinarum</i> Hance and <i>in silico</i> molecular dynamics

Lee, Ji Sun,Kim, Jang Hoon,Han, Yoo Kyong,Ma, Jin Yeul,Kim, Young Ho,Li, Wei,Yang, Seo Young Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.120 No.2

<P><B>Abstract</B></P> <P>Six diarylheptanoids (<B>1</B>–<B>6</B>) and two flavonoids (<B>7</B> and <B>8</B>) derived from <I>Alpinia officinarum</I> were evaluated for their ability to inhibit acetylcholinesterase. Compound <B>1</B> showed the highest degree of inhibition, with an IC<SUB>50</SUB> of approximately 2 μM, followed by moderate degrees of inhibition by <B>2</B>, <B>4</B> and <B>7</B>, with IC<SUB>50</SUB> values ranging from 20 to 40 μM. The remaining isolated compounds <B>3</B>, <B>5</B>, <B>6</B> and <B>8</B> had IC<SUB>50</SUB> values greater than 50 μM. Enzyme kinetic studies showed that the compounds with high or moderate activity were competitive inhibitors, anchored to the active site of acetylcholinesterase. In particular, compounds <B>1</B> and <B>2</B> were docked at slightly different positions from those occupied by <B>4</B> and <B>7</B>. Furthermore, molecular dynamics studies showed that compound <B>1</B> maintained its interactions with residues Thr74 and Phe295 throughout the simulation trajectory. Our findings suggest that compound <B>1</B> is a potential therapeutically relevant inhibitor of acetylcholinesterase.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Six diarylheptanoids (<B>1</B>–<B>6</B>) and two flavonoids (<B>7</B> and <B>8</B>) were isolated from <I>Alpinia officinarum</I>. </LI> <LI> Compound <B>1</B> showed acetylcholinesterase inhibitory activity with IC<SUB>50</SUB> value of approximately 2 μM. </LI> <LI> Compounds <B>1</B>, <B>2</B>, <B>4</B>, and <B>7</B> inhibited the catalytic reaction of acetylcholinesterase as competitive mode. </LI> <LI> Computational simulation study suggested the predicted binding position of the compound <B>1</B> with catalytic site of receptor. </LI> </UL> </P>

Design and applications of fluorescent detectors for peroxynitrite

Wang, Shan,Chen, Liyan,Jangili, Paramesh,Sharma, Amit,Li, Wei,Hou, Ji-Ting,Qin, Caiqin,Yoon, Juyoung,Kim, Jong Seung Elsevier 2018 Coordination chemistry reviews Vol.374 No.-

<P><B>Abstract</B></P> <P>Peroxynitrite (ONOO<SUP>−</SUP>) is one of the endogenous reactive oxygen species (ROS), which causes damage to a wide array of molecular components in the cells, including DNA and proteins, owing to its high oxidizing as well as nitrating properties. However, the precise pathogenic roles played by this substance in biological systems have not yet been elucidated completely owing to its short lifetime, high reactivity, low concentration and elusive nature in the <I>in vivo</I> applications. Thus, the development of more sensitive and selective techniques for detecting ONOO<SUP>−</SUP>, with high biocompatibilities, sensitivities, and site-specificities, is a significant goal. This review summarizes the recent advances that have been made in developing fluorescent sensors for ONOO<SUP>−</SUP> and their biological applications in diverse living systems.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The general significance of ONOO<SUP>−</SUP> detection. </LI> <LI> The design strategies of functional ONOO<SUP>−</SUP> probes. </LI> <LI> The diverse platforms to design ONOO<SUP>−</SUP> probes, including small molecules, proteins and nanocarriers. </LI> <LI> The diverse biological applications of fluorescent ONOO<SUP>−</SUP> probes. </LI> <LI> Perspectives and potential future directions. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>In this review, the development of fluorescent probes for peroxynitrite detection since 2013 is described. The chemical sensor’s designs has been classified by their reaction based sensing patterns.</P> <P>[DISPLAY OMISSION]</P>

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

( Ji-wei Ma ),( Yong Zhang ),( Ji-cheng Ye ),( Ru Li ),( Yu-lin Wen ),( Jian-xian Huang ),( Xue-yun Zhong ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.2

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

Effect of Glutamate on the Vestibulo-Solitary Projection after Sodium Nitroprusside-Induced Hypotension in Conscious Rats

Li, Li-Wei,Ji, Guang-Shi,Yang, Yan-Zhao,Ameer, Abdul Nasir,Kim, Min Sun,Park, Byung Rim,Jin, Yuan-Zhe The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.3

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

Novel arylhydrazone derivatives bearing a rhodanine moiety: synthesis and evaluation of their antibacterial activities

Li, Wei,Zheng, Chang-Ji,Sun, Liang-Peng,Song, Ming-Xia,Wu, Yan,Li, Yin-Jing,Liu, Yi,Piao, Hu-Ri 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.7

A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of $2-4{\mu}g/mL$ against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at $64{\mu}g/mL$.

Novel arylhydrazone derivatives bearing a rhodanine moiety: synthesis and evaluation of their antibacterial activities

Wei Li,Chang-Ji Zheng,Liang-Peng Sun,Ming-Xia Song,Yan Wu,Yin-Jing Li,Yi Liu,Hu-Ri Piao 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.7

A series of arylhydrazone derivatives bearing arhodanine moiety have been synthesized, characterized, andevaluated as antibacterial agents. Some of these compoundsshowed potent antibacterial activities against several differentstrains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIkand IIIk were identified as the most effective, with minimuminhibitory concentration values of 2–4 lg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcusaureus. None of the compounds exhibited any activityagainst the Gram-negative bacteria Escherichia coli 1356 at64 lg/mL.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

Xiong, Wei,Jiang, Yong-Xin,Ai, Yi-Qin,Liu, Shan,Wu, Xing-Rao,Cui, Jian-Guo,Qin, Ji-Yong,Liu, Yan,Xia, Yao-Xiong,Ju, Yun-He,He, Wen-Jie,Wang, Yong,Li, Yun-Fen,Hou, Yu,Wang, Li,Li, Wen-Hui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Fei Li,Xin-ji Li,Li Qiao,Fei Shi,Wen Liu,You Li,Yu-ping Dang,Weijie Gu,Xiao-gang Wang,Wei Liu 생화학분자생물학회 2014 Experimental and molecular medicine Vol.46 No.-

Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Ma, Ji-wei,Zhang, Yong,Ye, Ji-cheng,Li, Ru,Wen, Yu-Lin,Huang, Jian-xian,Zhong, Xue-yun The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.2

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

HIV-negative plasmablastic lymphoma: report of 8 cases and a comprehensive review of 394 published cases

Ya-Jun Li,Ji-Wei Li,Kai-Lin Chen,Jin Li,Mei-Zuo Zhong,Xian-Ling Liu,Ping-Yong Yi,Hui Zhou 대한혈액학회 2020 Blood Research Vol.55 No.1

BackgroundHuman immunodeficiency virus (HIV)-negative plasmablastic lymphoma (PBL) is a rare entity of diffuse large B-cell lymphoma (DLBCL). The clinicopathological features of and optimal treatment for HIV-negative PBL remain largely unknown.MethodsTo gain insight into this distinct lymphoma, we summarized the clinicopathologic charac-teristics of 8 unpublished HIV-negative PBLs and performed a comprehensive review of 394 published cases.ResultsOf the 8 unpublished PBLs, the median patient age was 53.0 years. Four patients pre-sented with stage IV disease. All 8 patients showed a plasma cell-like immunophenotype. Of the six patients who received anthracycline-based chemotherapy, including two who received bortezomib, three patients achieved a continuous complete response, two pa-tients died due to disease progression, and one patient was lost to follow-up. The other two patients achieved continuous complete response after receiving chemotherapy com-bined with radiotherapy and surgery. Of the 402 patients, the majority were male, with a mean age of 58.0 years. EBV infection was detected in 55.7% of the patients. The median survival times of the patients who received CHOP or CHOP-like regimens and intensive regimens were not reached and 23.0 months, respectively, and the intensive regimen did not improve the survival outcome (P=0.981). Multivariate analysis showed that EBER remained the only independent factor affecting overall survival (OS).ConclusionHIV-negative PBL is a distinct entity with a predilection for elderly and immunosup-pressed individuals. Intensive chemotherapy had no apparent survival benefits over the CHOP regimen in terms of OS; the prognosis of this disease is poor with current chemo-therapy methods, and treatment remains a challenge.