Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis

( Xiao-qiang Li ),( Xiao-xiao Liu ),( Xue-ying Wang ),( Yan-hua Xie ),( Qian Yang ),( Xin-xin Liu ),( Yuan-yuan Ding ),( Wei Cao ),( Si-wang Wang ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3

The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

A cross-entropy algorithm based on Quasi-Monte Carlo estimation and its application in hull form optimization

Liu Xin,Zhang Heng,Liu Qiang,Dong Suzhen,Xiao Changshi 대한조선학회 2021 International Journal of Naval Architecture and Oc Vol.13 No.1

Simulation-based hull form optimization is a typical HEB (high-dimensional, expensive computationally, black-box) problem. Conventional optimization algorithms easily fall into the “curse of dimensionality” when dealing with HEB problems. A recently proposed Cross-Entropy (CE) optimization algorithm is an advanced stochastic optimization algorithm based on a probability model, which has the potential to deal with high-dimensional optimization problems. Currently, the CE algorithm is still in the theoretical research stage and rarely applied to actual engineering optimization. One reason is that the Monte Carlo (MC) method is used to estimate the high-dimensional integrals in parameter update, leading to a large sample size. This paper proposes an improved CE algorithm based on quasi-Monte Carlo (QMC) estimation using high-dimensional truncated Sobol subsequence, referred to as the QMC-CE algorithm. The optimization performance of the proposed algorithm is better than that of the original CE algorithm. With a set of identical control parameters, the tests on six standard test functions and a hull form optimization problem show that the proposed algorithm not only has faster convergence but can also apply to complex simulation optimization problems.

Evaluation of insecticidal activity of the essential oil of Allium chinense G. Don and its major constituents against Liposcelis bostrychophila Badonnel

Xin Chao Liu,Xiao Nan Lu,Qi Zhi Liu,Zhi Long Liu 한국응용곤충학회 2014 Journal of Asia-Pacific Entomology Vol.17 No.4

Water-distilled essential oil from the dried bulbs of Allium chinense (Liliaceae) was analyzed by gaschromatography–mass spectrometry (GC–MS). Eighteen compounds, accounting for 98.4% of the total oil,were identified and the main components of the essential oil of A. chinense were methyl allyl trisulfide(30.7%), dimethyl trisulfide (24.1%), methyl propyl disulfide (12.8%) and dimethyl disulfide (9.6%) followed bymethyl allyl disulfide (3.4%) and methyl propyl trisulfide (3.6%). The essential oil exhibited contact toxicityagainst the booklice (Liposcelis bostrychophila) with an LC50 value of 441.8 μg/cm2 while the two major constituents,dimethyl trisulfide and methyl propyl disulfide had LC50 values of 153.0 μg/cm2 and 738.0 μg/cm2 againstthe booklice, respectively. The essential oil of A. chinense possessed strong fumigant toxicity against the booklicewith an LC50 value of 186.5 μg/l while methyl allyl trisulfide (LC50=90.4 μg/l) and dimethyl trisulfide (LC50=114.2 μg/l) exhibited stronger fumigant toxicity than methyl propyl disulfide (LC50= 243.4 μg/l) and dimethyldisulfide (LC50= 340.8 μg/l) against the booklice. The results indicated that the essential oil and itsmajor constituentshave potential for development into natural insecticides or fumigants for control of insects in stored grains.

Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis

Li, Xiao-Qiang,Liu, Xiao-Xiao,Wang, Xue-Ying,Xie, Yan-Hua,Yang, Qian,Liu, Xin-Xin,Ding, Yuan-Yuan,Cao, Wei,Wang, Si-Wang The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3

The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), ${\alpha}$-bromo-4-methylcinnamaldehyde (4), and ${\alpha}$-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of $11.38{\pm}2.22{\mu}M$ and $2.12{\pm}0.37{\mu}M$, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao, Cheng-Xiao,Liu, Ming,Xu, Yong,Yang, Kuo,Wei, Dong,Shi, Xiao-Hong,Yang, Fan,Zhang, Yao-Guang,Wang, Xin,Liang, Si-Ying,Zhao, Fan,Zhang, Yu-Rong,Wang, Na-Na,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Yuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, $P=7.3{\times}10^{-5}$), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, $Padj=1.1{\times}10^{-4}$). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, $P=1.0{\times}10^{-5}$) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

Relation between Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-α Expression in Invasive Ductal Breast Cancer Patients and Correlations with Prognosis

Yan, Jian,Liu, Xiao-Long,Han, Lu-Zhe,Xiao, Gang,Li, Ning-Lei,Deng, Yi-Nan,Yin, Liang-Chun,Ling, Li-Juan,Yu, Xiao-Yuan,Tan, Can-Liang,Huang, Xiao-Ping,Liu, Li-Xin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.

D-Galactose Induces a Mitochondrial Complex I Deficiency in Mouse Skeletal Muscle: Potential Benefits of Nutrient Combination in Ameliorating Muscle Impairment

Liao Chang,Xin Liu,Jing Liu,Hua Li,Yanshen Yang,Jia Liu,Zihao Guo,Ke Xiao,Chen Zhang,Jiankang Liu,Xi Zhao-Wilson,Jiangang Long 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.3

Accumulating research has shown that chronic D-galactose (D-gal) exposure induces symptoms similar to natural aging in animals. Therefore, rodents chronically exposed to D-gal are increasingly used as a model for aging and delay-of-aging pharmacological research. Mitochondrial dysfunction is thought to play a vital role in aging and age-related diseases; however, whether mitochondrial dysfunction plays a significant role in mice exposed to D-gal remains unknown. In the present study, we investigated cognitive dysfunction, locomotor activity, and mitochondrial dysfunction involved in D-gal exposure in mice. We found that D-gal exposure (125 mg/kg/day, 8 weeks) resulted in a serious impairment in grip strength in mice, whereas spatial memory and locomotor coordination remained intact. Interestingly, muscular mitochondrial complex I deficiency occurred in the skeletal muscle of mice exposed to D-gal. Mitochondrial ultrastructure abnormality was implicated as a contributing factor in D-gal-induced muscular impairment. Moreover, three combinations (A, B, and C) of nutrients applied in this study effectively reversed D-gal-induced muscular impairment. Nutrient formulas B and C were especially effective in reversing complex I dysfunction in both skeletal muscle and heart muscle. These findings suggest the following: (1) chronic exposure to D-gal first results in specific muscular impairment in mice, rather than causing general, premature aging; (2) poor skeletal muscle strength induced by D-gal might be due to the mitochondrial dysfunction caused by complex I deficiency; and (3) the nutrient complexes applied in the study attenuated the skeletal muscle impairment, most likely by improving mitochondrial function.

Arylazolyl(azinyl)thioacetanilide. Part 9#: Synthesis and Biological Investigation of Thiazolylthioacetamides Derivatives as a Novel Class of Potential Antiviral Agents

Peng Zhan,Xinyong Liu,Liu Wang,Hong Liu,Xuwang Chen,Xiao Li,Xin Jiang,Qiangqiang Zhang,Christophe Pannecouque,Lieve Naesens,Erik De Clercq,Ailin Liu,Guanhua Du 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

In continuation of our endeavor to develop new, potent, selective and less toxic antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl) thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route and evaluated for their anti-HIV activities against wild-type virus and clinically relevant mutant strains, and for their anti-influenza virus activities against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The selected active compounds were also assayed for their enzymic inhibitory activities. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC50 values in micromolar range. Two 2-amino substituted thiazole derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in MDCK cells with EC50 values much lower than that of oseltamivir carboxylate, ribavirin, amantadine and rimantadine. Though the mechanism of actions is still unclear, these novel thiazolylthioacetamides might serve as original leads for further pharmacological investigations as potential therapeutic agents against HIV-1 or influenza virus.

Self-assembled wide bandgap nanocoatings enabled outstanding dielectric characteristics in the sandwich-like structure polymer composites

Wang Tian-Yu,Li Xiao-Fen,Liu Shu-Ming,Liu Bai-Xin,Liang Xi-Dong,Li Shunning,Zhang Gui-Xin,Liu Jian-Bo,Dang Zhi-Min 나노기술연구협의회 2022 Nano Convergence Vol.9 No.55

Polymer dielectrics are insulators or energy storage materials widely used in electrical and electronic devices. Polymer dielectrics are needed with outstanding dielectric characteristics than current technologies. In this study, the self-assembly of boron nitride nanosheets (BNNSs) was applied to form an inorganic–organic nanocoating on various common polymer dielectrics. It is inexpensive and easy to fabricate this thin coating on a large scale. The coating has a wide bandgap and thus can significantly improve the breakdown strength of polymer dielectrics. The charge characteristics and trapping parameters of nano-domains on the surfaces of polymer dielectrics were measured, and the coating had shallow trap levels. This facilitated the dissipation of surface charges and thus greatly increased the flashover voltage. The coating also effectively improved the temperature stability and dielectric constant of the polymer dielectric. This nanocoating shows potential as a method to effectively improve the dielectric characteristics of polymer dielectrics and outperform existing composite polymer dielectrics, which are crucial for large-scale applications in energy storage and power and electronic devices.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

Zhang, Yu-Rong,Xu, Yong,Yang, Kuo,Liu, Ming,Wei, Dong,Zhang, Yao-Guang,Shi, Xiao-Hong,Wang, Jian-Ye,Yang, Fan,Wang, Xin,Liang, Si-Ying,Zhao, Cheng-Xiao,Wang, Fei,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Zh Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.