Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers

Qi Fei-Yan,Zhu Zhou-Hai,Li Meng,Guan Ying,Peng Qi-Yuan,Lu She-Ming,Liu Zhi-Hua,Wang Ming-Feng,Miao Ming-Ming,Chen Zhang-Yu,Li Xue-Mei,Bai Jie,Yao Jian-Hua 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear. Objective: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population. Methods: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293. Results: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X2 = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X2 = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells. Conclusion: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.

Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine constructed by reverse genetic manipulation

Feng Wen,Ji-Hong Ma,Hai Yu,Fu-Ru Yang,Meng Huang,Yan-Jun Zhou,Ze-Jun Li,Guangzhi Tong 대한수의학회 2014 JOURNAL OF VETERINARY SCIENCE Vol.15 No.3

Novel reassortant H3N2 swine influenza viruses (SwIV)with the matrix gene from the 2009 H1N1 pandemic virushave been isolated in many countries as well as duringoutbreaks in multiple states in the United States, indicatingthat H3N2 SwIV might be a potential threat to public health. Since southern China is the world’s largest producer of pigs,efficient vaccines should be developed to prevent pigs fromacquiring H3N2 subtype SwIV infections, and thus limit thepossibility of SwIV infection at agricultural fairs. In thisstudy, a high-growth reassortant virus (GD/PR8) wasgenerated by plasmid-based reverse genetics and tested as acandidate inactivated vaccine. The protective efficacy of thisvaccine was evaluated in mice by challenging them withanother H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05(H3N2) (HLJ/05)]. Prime and booster inoculation withGD/PR8 vaccine yielded high-titer serum hemagglutinationinhibiting antibodies and IgG antibodies. Completeprotection of mice against H3N2 SwIV was observed, withsignificantly reduced lung lesion and viral loads invaccine-inoculated mice relative to mock-vaccinatedcontrols. These results suggest that the GD/PR8 vaccine mayserve as a promising candidate for rapid intervention ofH3N2 SwIV outbreaks in China.

A novel M2e-multiple antigenic peptide providing heterologous protection in mice

Feng Wen,Ji-Hong Ma,Hai Yu,Fu-Ru Yang,Meng Huang,Yan-Jun Zhou,Ze-Jun Li,Xiu-Hui Wang,Guo-Xin Li,Yi-Feng Jiang,Wu Tong,Guangzhi Tong 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.1

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.

Phytochemistry and pharmacology of natural prenylated flavonoids

Hua-Wei Lv,Qiao-Liang Wang,Meng Luo,Meng-Di Zhu,Hui-Min Liang,Wen-Jing Li,Hai Cai,Zhong-Bo Zhou,Hong Wang,Sheng-Qiang Tong,Xing-Nuo Li 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.4

Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value.

Optimized Transformation of Streptomyces sp. ATCC 39366 Producing Leptomycin by Electroporation

Yong-Qiang Fan,Hong-Jian Liu,Li Yan,Yu-Shi Luan,Hai-Meng Zhou,Jun-Mo Yang,Shang-Jun Yin,Yu-Long Wang 한국미생물학회 2013 The journal of microbiology Vol.51 No.3

Streptomyces sp. ATCC 39366 produces leptomycin derivatives. Leptomycin B, a potent and specific inhibitor against the export of nuclear proteins, is the main product; however, the introduction of DNA into this strain is almost impossible, which has impeded its further use. We developed a Streptomyces sp. ATCC 39366 transformation protocol to introduce foreign DNA via electroporation. Various conditions were examined, including treatments of the cell wall with weakening agents, electroporation parameters, and DNA content. We found that only plasmid DNA isolated from a dam- ET12567 strain resulted in successful transformation. The mycelium growing in a yeast-peptone-dextrose medium supplemented with 1% glycine at 28°C on a rotary shaker (220 rpm) was more dispersed than those without supplementation and prone to electroporation. The maximum transformation efficiency of 8×102 CFU/μg plasmid DNA was obtained at a field strength of 13 kV/cm with a time constant of 13 ms (25-μF capacitor; parallel resistance, 600 Ω) using 1-mm electrocuvettes. The results of the transformations of two other Streptomyces species indicated that the optimized conditions established in this study might only be applicable to Streptomyces sp. ATCC 39366. However, this is the first report of successful transformation of Streptomyces sp. ATCC 39366, and will facilitate the construction of a gene knockout mutant in Streptomyces sp. ATCC 39366 to produce series of new leptomycin derivatives.

Effects of L-malic acid on alpha-glucosidase: inhibition kinetics and computational molecular dynamics simulations.

Gou, Lin,Zhan, Yi,Lee, Jinhyuk,Li, Xuan,Lü,, Zhi-Rong,Zhou, Hai-Meng,Lu, Hang,Wang, Xi-Yao,Park, Yong-Doo,Yang, Jun-Mo Humana Press 2015 Applied biochemistry and biotechnology Vol.175 No.4

<P>The inhibitory effect of L-malic acid (MA) on alpha-glucosidase (EC 3.2.1.20) was investigated by combination study between inhibition kinetics and computational simulations. The results from the serial kinetics demonstrated that MA could directly inactivate the enzyme activity in a dose-dependent manner and a typical non-competitive type, as well as in a fast inactivate process without detectable time course. The tertiary conformation study with an application of spectrofluorimetry showed that MA modulated the tertiary structural conformation of alpha-glucosidase both on the overall and on regional active site pocket, which monitored by red-shift intrinsic fluorescence peak with decreases intensities, and the significant intensity increasing of 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence, respectively. To have more insight, we also adapted the computational molecular dynamics (MD) simulations. The results showed that MA was located in the entrance of active pocket for the catalytic reaction and blocked the passage of substrate. It confirmed that MA inhibits as a non-competitive type, not direct docking to the glucose binding site. Our study provides important molecular mechanisms to figure out alpha-glucosidase inhibition that might associate to development of type 2 diabetes mellitus drug.</P>

Trifluoroethanol-induced changes in activity and conformation of manganese-containing superoxide dismutase.

Yin, Shang-Jun,L?, Zhi-Rong,Park, Daeui,Chung, Hae Young,Yang, Jun-Mo,Zhou, Hai-Meng,Qian, Guo-Ying,Park, Yong-Doo Humana Press 2012 Applied biochemistry and biotechnology Vol.166 No.2

<P>Superoxide dismutase (SOD, EC 1.15.1.1) plays an important role in antioxidant defense in organisms exposed to oxygen. However, there is a lack of research into the regulation of SOD activity and structural changes during folding, especially for SOD originating from extremophiles. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of manganese-containing SOD (Mn-SOD) from Thermus thermophilus. TFE decreased the degree of secondary structure of Mn-SOD, which directly resulted in enzyme inactivation and disrupted the tertiary structure of Mn-SOD. The kinetic studies showed that TFE-induced inactivation of Mn-SOD is a first-order reaction and that the regional Mn-contained active site is very stable compared to the overall structure. We further simulated the docking between Mn-SOD and TFE (binding energy for Dock 6.3, -9.68 kcal/mol) and predicted that the LEU9, TYR13, and HIS29 residues outside of the active site interact with TFE. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of TFE and allow us to describe ligand binding via inhibition kinetics combined with computational predictions.</P>

Kinetics and computational docking studies on the inhibition of tyrosinase induced by oxymatrine.

Liu, Xiao-Xia,Sun, Shi-Qing,Wang, Yu-Jie,Xu, Wei,Wang, Yi-Fang,Park, Daeui,Zhou, Hai-Meng,Han, Hong-Yan Humana Press 2013 Applied biochemistry and biotechnology Vol.169 No.1

<P>A combination of enzymatic inhibition kinetics and computational prediction was employed to search for an effective inhibitor of tyrosinase. We found that oxymatrine significantly inhibited tyrosinase, and that this reaction was not accompanied by detectable conformational changes. Kinetic analysis showed that oxymatrine reversibly inhibited tyrosinase in a mixed-type manner. Measurements of intrinsic and ANS-binding fluorescences showed that oxymatrine did not induce any conspicuous changes in the tertiary structure. We also conducted a docking simulation between tyrosinase and oxymatrine using two docking programs, Dock6.3 and AutoDock4.2 (binding energy was -118.81 kcal/mol for Dock6 and -8.04 kcal/mol for AutoDock4). The results also suggested that oxymatrine interacts mostly with the residues of CYS83 and HIS263 in the active site of tyrosinase. This strategy of predicting tyrosinase inhibition by simulation of docking coupling with kinetics may prove useful in screening for potential tyrosinase inhibitors. Knowledge of tyrosinase inhibition can provide medical, cosmetic, and agricultural applications. Our study suggests that oxymatrine is an important agent for various applications related to pigment formation.</P>