Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

( Yaodong Liu ),( Sibtain Ahmed ),( Yaowei Fang ),( Meng Chen ),( Jia An ),( Guang Yang ),( Xiaoyue Hou ),( Jing Lu ),( Qinwen Ye ),( Rongjun Zhu ),( Qitong Liu ),( Shu Liu ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soil-borne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 μM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 μg/ml and minimum fungicidal concentration (MFC) at 520 μg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Liu, Fei,Pu, Xiao-Yun,Huang, Shao-Guang,Xiang, Gui-Ming,Jiang, Dong-Neng,Hou, Gou,Huang, Di-Nan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.

Liposomal honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic antitumor efficacy without increasing toxicity

Jia Hu,Li Liu,Xiang Chen,Ping Chen,Guang-li Yang,Wen-li Hou,Ming-hai Tang,Fan Zhang,Xian-huo Wang,Xia Zhao,Yu-quan Wei,Li-juan Chen 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.6

Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy. Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study

Wang Qi,Dai Huajie,Hou Tianzhichao,Hou Yanan,Wang Tiange,Lin Hong,Zhao Zhiyun,Li Mian,Zheng Ruizhi,Wang Shuangyuan,Lu Jieli,Xu Yu,Liu Ruixin,Ning Guang,Wang Weiqing,Bi Yufang,Zheng Jie,Xu Min 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family, <i>Desulfovibrio</i> genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all <i>P</i><0.044). The causal associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas <i>Desulfovibrio</i> genus was negatively associated with ApoB/ApoA1 (all <i>P</i><0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (<i>P</i>=0.028) and 4.6% (<i>P</i>=0.033); the association between <i>Desulfovibrio</i> genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (<i>P</i>=0.019), 4.2% (<i>P</i>=0.035), and 9.1% (<i>P</i>=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Systematic Review and Meta-Analysis of Antibiotic-Impregnated Shunt Catheters on Anti-Infective Effect of Hydrocephalus Shunt

Zhou, Wen-xiu,Hou, Wen-bo,Zhou, Chao,Yin, Yu-xia,Lu, Shou-tao,Liu, Guang,Fang, Yi,Li, Jian-wen,Wang, Yan,Liu, Ai-hua,Zhang, Hai-jun The Korean Neurosurgical Society 2021 Journal of Korean neurosurgical society Vol.64 No.2

Objective : Shunt infection is a common complication while treating hydrocephalus. The antibiotic-impregnated shunt catheter (AISC) was designed to reduce shunt infection rate. A meta-analysis was conducted to study the effectiveness of AISCs in reduction of shunt infection in terms of age, follow-up time and high-risk patient population. Methods : This study reviewed literature from three databases including PubMed, EMBASE, and Cochrane Library (from 2000 to March 2019). Clinical studies from controlled trials for shunt operation were included in this analysis. A subgroup analysis was performed based on the patient's age, follow-up time and high-risk population. The fixed effect in RevMan 5.3 software (Cochrane Collaboration) was used for this meta-analysis. Results : This study included 19 controlled clinical trials including 10105 operations. The analysis demonstrated that AISC could reduce the infection rate in shunt surgery compared to standard shunt catheter (non-AISC) from 8.13% to 4.09% (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.58; p=0.01; I2=46%). Subgroup analysis of different age groups showed that AISC had significant antimicrobial effects in all three groups (adult, infant, and adolescent). Follow-up time analysis showed that AISC was effective in preventing early shunt infections (within 6 months after implant). AISC is more effective in high-risk population (OR, 0.24;95% CI, 0.14-0.40; p=0.60; I2=0%) than in general patient population. Conclusion : The results of meta-analysis indicated that AISC is an effective method for reducing shunt infection. We recommend that AISC should be considered for use in infants and high-risk groups. For adult patients, the choice for AISC could be determined based on the treatment cost.

Realizing the empirical mode decomposition by the adaptive stochastic resonance in a new periodical model and its application in bearing fault diagnosis

Jingling Zhang,Dawen Huang,Jianhua Yang,Hou-guang Liu,Xiaole Liu 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.10

We investigate a multi-frequency signal that cannot be decomposed by empirical mode decomposition directly. Moreover, this kind of signal in the noisy background cannot be decomposed successfully by the traditional stochastic resonance with bistable system yet. We propose a new method which using the empirical mode decomposition combined the adaptive stochastic resonance in a new periodical model to solve this problem. The results show that the proposed method decomposes the multi-frequency signal perfectly. Meanwhile, the general scale transformation and random particle swarm optimization algorithm are used to help obtain a better result in the process of optimization. Through using this new method, the simulation results are satisfactory. More importantly, this new method also shows good performance in the application of bearing fault diagnosis.

Workspace analysis of 3-CPS parallel micro-manipulator for mirror active adjusting platform

Gang Cheng,Bing-jing Qiu,De-hua Yang,Hou-guang Liu 대한기계학회 2013 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.27 No.12

In order to adjust telescope mirrors with high precision, a 3 cylindrical-prismatic-spherical (CPS) parallel micro-manipulator with 6 degrees-of-freedom (DOF) and partial decoupling is proposed. Structure characteristics of the micro-manipulator were analyzed and the kinematic equations were derived based on Euler method. To avoid tedious derivation, Jacobian matrix with screw theory representing the input and output relation of micro-manipulator is established by using velocity influence coefficient method. Combining topological structure characteristics of the 3-CPS parallel micro-manipulator, the solving procedures of workspace are obtained. Moreover, the position workspace with a given orientation and the orientation workspace with a given translation position are constructed by numerical simulations. The workspace range is chosen as the optimization goal of structure parameters, and the circumcircle radius ratio of base and moving platform and the lengths of each sub-link are optimized. The maximum condition number and the minimum singular value are chosen as the precision indexes to analyze the precision performance of the workspace. Then, the properties of the position workspaces with various orientations and the orientation workspaces with various positions are simulated numerically, and the simulation results prove that the 3-CPS parallel micro-manipulator has an ability to achieve high precision operations. This research provides a workspace modeling and optimization method for the practical application in telescope mirror adjustment or other fields requiring high precision.

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

Zhang, Jing-Wen,Yu, Wan-Jia,Sheng, Xiao-Min,Chang, Fu-Hou,Bai, Tu-Ya,Lv, Xiao-Li,Wang, Guang,Liu, Su-Zhen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Purpose: To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibility among Mongolian and Han populations in the Inner Mongolian region. Materials and Methods: CYP2E1 and NAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. Results: (1) Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1 RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178-1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared with rapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1 together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1 c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CC and NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lung cancer risk than others with rapid acetylation. Conclusions: Disequilibrium distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2 slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lung cancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasing lung cancer risk.