Mutant IDH1 Enhances Temozolomide Sensitivity via Regulation of the ATM/CHK2 Pathway in Glioma

Lin Lin,Jinquan Cai,Zixiao Tan,Xiangqi Meng,Ruiyan Li,Yang Li,Chuanlu Jiang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.2

Purpose Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate. Materials and MethodsIDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation.ResultsWe established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC50 of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment. ConclusionThese results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

Scutellaria Extract Decreases the Proportion of Side Population Cells in a Myeloma Cell Line by Down-regulating the Expression of ABCG2 Protein

Lin, Mei-Gui,Liu, Li-Ping,Li, Chen-Yin,Zhang, Meng,Chen, Yuling,Qin, Jian,Gu, Yue-Yu,Li, Zhi,Wu, Xin-Lin,Mo, Sui-Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

Four-Hour Fasting for Semifluids and 2-Hour Fasting for Water Improves the Patient Experience of Esophagogastroduodenoscopy: A Randomized Controlled Trial

Cai Meng-Xi,Gao Ye,Li Li,Feng Wen,Wang Yi-Lin,Li Zhao-Shen,Xin Lei,Wang Luo-Wei 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.3

Background/Aims: We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol. Methods: In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting. Results: One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the “4+2” protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0–5.0] vs 4.0 [4.0–5.0], p=0.266). No adverse events were observed during the study. Conclusions: The “4+2” protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD. (

Effects of Aqueous Extract of Schizandra Chinensis Fruit on Cadmium-Induced Change of Monoamine Neurotransmitters in Rats

Zheng Lin Zhao,Guang Wen Zhao,Li Li,Meng Quan Li,Li Xin Guan,Xu Dong Yang,Hou Zhong Li,Feng Lin,Jong Rok Lee,Rong Jie Zhao 한국독성학회 2009 Toxicological Research Vol.25 No.1

The effects of aqueous extract of Schizandra Chinensis Fruit (AESC) on cadmium-induced changes of monoamine neurotransmitters in the different brain regions of adult rats were investigated. Male rats were received intraperitoneal (i.p.) administration of CdCl₂ (0.6 ㎎/㎏/d) for 21 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA) in striatum and serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in cortex were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Cd intoxicated rats (P < 0.05), while pretreatment with AESC (20 ㎎/㎏/d or 60 mg/kg/d, p.o., 30 min before CdCl₂) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC significantly increased the reduction of glutathione contents and superoxide dismutase activities in cortex induced by CdCl₂. These results suggest that AESC ameliorates Cd-induced depletion of monoamine neurotransmitters in brain through its antioxidant activity.

The Gender-Sensitive Social Risk Factors for Internet Addiction in College Undergraduate Students

Xia Lin,Jing-yan Gu,Wan-jun Guo,Ya-jing Meng,Hui-yao Wang,Xiao-jing Li,Wei Deng,Lian-sheng Zhao,Xiao-hong Ma,Ming-li Li,Ting Chen,S,K,Cheng,Tao Li 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.7

Objective The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. Methods Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. Results We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. Conclusion IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

Portable Laser Doppler Flowmeter for Microcirculation Detection

Chang-Lin Hu,Meng-Lin Li,Zhan-Sheng Lin,Yen-Yu Chen,Yuan-Hsiang Lin 대한의용생체공학회 2013 Biomedical Engineering Letters (BMEL) Vol.3 No.2

Purpose The microcirculatory system of the human body is closely related to its physiological conditions. The laser Doppler flowmeter can detect symptoms through variations in the microcirculation; however, the present commercial Doppler flowmeter is very expensive, heavy, and inconvenient to carry. Therefore, an inexpensive, small, and portable laser Doppler flowmeter is proposed. Methods In this study, we designed a laser Doppler flowmeter transmitting receiving module based on the fundamental principles of laser Doppler, using a common computer for flow calculation. A self-designed correction system was used to validate the portable laser Doppler flowmeter. Results The coefficient of correlation between the mean frequency offset <ω> of the flowmeter and the actual mimicked blood flow rate reached a high value of R = 0.99, and the variations in microcirculation flow could be accurately measured. Conclusions The results proved that the low-cost portable laser Doppler flowmeter can be used extensively in early symptom detection for disease prevention and control.

Effects of Aqueous Extract of Schizandra Chinensis Fruit on Cadmium-Induced Change of Monoamine Neurotransmitters in Rats

Zhao, Zheng Lin,Zhao, Guang Wen,Li, Li,Li, Meng Quan,Guan, Li Xin,Yang, Xu Dong,Li, Hou Zhong,Lin, Feng,Lee, Jong-Rok,Zhao, Rong Jie Korean Society of ToxicologyKorea Environmental Mu 2009 Toxicological Research Vol.26 No.1

The effects of aqueous extract of Schizandra Chinensis Fruit (AESC) on cadmium-induced changes of monoamine neurotransmitters in the different brain regions of adult rats were investigated. Male rats were received intraperitoneal (i.p.) administration of CdCl2 (0.6 mg/kg/d) for 21 days and sacrificed 7 days after the last administration. Concentrations of norepinephrine (NE), dopamine (DA) in striatum and serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) in cortex were measured by HPLC. There were significant decreases of NE, DA, 5-HT and 5-HIAA in Cd intoxicated rats (P < 0.05), while pretreatment with AESC (20 mg/kg/d or 60 mg/kg/d, p.o., 30 min before $CdCl_2$) greatly inhibited the decrease of monoamine transmitters, respectively (P < 0.05). Also, AESC significantly increased the reduction of glutathione contents and superoxide dismutase activities in cortex induced by $CdCl_2$. These results suggest that AESC ameliorates Cd-induced depletion of monoamine neurotransmitters in brain through its antioxidant activity.

Seroprevalence of Encephalitozoon cuniculi and Toxoplasma gondii in domestic rabbits (Oryctolagus cuniculus) in China

Qing-Feng Meng,Wei-Lin Wang,Xiao-Ting Ni,Hai-Bin Li,Gui-Zhe Yao,Xiao-Lin Sun,Wei-Li Wang,Wei Cong 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.6

The breeding of domestic rabbits (Oryctolagus cuniculus) for human consumption has a long tradition in China. Infections that can affect the production of meat or even be transmitted from animals to humans are important to monitor, especially for public health reasons as well as for their impact on animal health. Thus, a total of 1,132 domestic rabbit sera from 4 regions in China were collected for serological screening for Encephalitozoon cuniculi and for Toxoplasma gondii by ELISA and modified agglutination test (MAT), respectively. Antibodies to E. cuniculi were detected in 248/1,132 (21.9%) sera tested while antibodies against T. gondii revealed a seroprevalence of 51/1,132 (4.5%). We believe that the present results are of epidemiological implications and public health importance due to the acknowledged susceptibility of humans to E. cuniculi and T. gondii infections. Therefore, routine screening tests of domestic rabbits are proposed considering the zoonotic potential of these parasites.

Synthesis and Structural Studies of an Organic Complex and its Association with BSA

Meng, Fa-Yan,Yu, Sheng-Rong,Liang, Li-Xi,Zhong, Xue-Ping,Wang, Li,Zhu, Jin-Mei,Lin, Cui-Wu Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.7

The self-assembly of one novel organic complex based on chlorogenic acid (HCA) and 2,2'-bipyridine (2,2'-bipy) has been synthesized and characterized. The complex achieved by hydrogen-bonding interactions, adopted a 1:1 stoichiometry in a solid state. The proton transfer occurred from the carboxyl oxygen to the aromatic nitrogen atom to form salts CA${\cdot}$(2,2'-Hbipy), the 2,2'-Hbipy molecule individually occupies the pseudo-tetragonum that is formed with CA. In this paper, the interactions of CA${\cdot}$(2,2'-Hbipy) with bovine serum albumin (BSA) were studied by fluorescence spectrometry. For CA${\cdot}$(2,2'-Hbipy), HCA and 2,2'-bipy, the average quenching constants for BSA were $2.4384{\times}10^4$, $4.653{\times}10^3$, and $3.059{\times}10^3\;L{\cdot}mol^{-1}$, respectively. The mechanism for protein fluorescence quenching is apparently governed by a static quenching process. The Stern-Volmer quenching constants and corresponding thermodynamic parameters ${\Delta}$H, ${\Delta}$G and ${\Delta}$S were calculated. The binding constants and the number of binding sites were also investigated. The conformational changes of BSA were observed from synchronous fluorescence spectra.

Syntheses, Crystal Structures, and Spectral Properties of Two Coordination Compounds Based on 1,2-Bis(benzimidazolyl)benzene

Meng, Fa-Yan,Jiang, Bing-Li,Lin, Cui-Wu,Wang, Li,Tan, Xiao-He Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

Two new benzimidazolyl-containing complexes have been synthesized by reactions of $Cu^{II}$ salts and 1,2-bis(benzimidazolyl) benzene ($H_2bbbz$) with two different dicarboxylate ligands. When phthalate acid ($H_2pt$) was employed as secondary ligand, a 0D molecular complex Cu$(H_2bbbz)(pt){\cdot}(H_2pt)$ (1)was furnished and when the secondary ligand was instead by a linear bridging ligand of terephthalic acid ($H_2tp$) a 1D zipper-like coordination polymer $[Cu(H_2bbbz)(tp){\cdot}2(C_2H_5OH){\cdot}H_2O]_n$ (2) was obtained, suggesting the structure-direction effect of the secondary dicarbxylate ligand. The preliminary investigation on the spectral properties of the complexes was also presented.