Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China

BACKGROUND: Individual response to medications varies significantly among different populations, and great progress in understanding the molecular basis of drug action has been made in the past 50 years. The field of pharmacogenomics seeks to elucidate inherited differences in drug disposition and effects. While we know that different populations and ethnic groups are genetically heterogeneous, we have not found any pharmacogenomics information regarding minority groups, such as the Tajik ethnic group in northwest China. RESULTS: We genotyped 85 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 100 unrelated, healthy Tajiks from the Xinjiang Uygur Autonomous Region and compared our data with HapMap data from four major populations around the world: Han Chinese (CHB), Japanese in Tokyo (JPT), Utah Residents with Northern and Western European Ancestry (CEU), and Yorubia in Ibadan, Nigeria (YRI). We found that Tajiks differed from CHB, JPT and YRI in 30, 32, and 32 of the selected VIP genotypes respectively (p < 0.005), while differences between Tajiks and CEU were found in only 6 of the genotypes (p < 0.005). Haplotype analysis also demonstrated differences between the Tajiks and the other four populations. CONCLUSION: Our results contribute to the pharmacogenomics database of the Tajik ethnic group and provide a theoretical basis for safer drug administration that may be useful for diagnosing and treating disease in this population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-014-0102-y) contains supplementary material, which is available to authorized users

Antitumor Effect of Zhihuang Fuzheng Soft Capsules on Tumor-Bearing Mice

Chinese medicines (CMs) have been shown to have some advantages in preventing and controlling tumors. In this study, we investigated the antitumor effect of ZFSC by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group, and the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group and showed a good dose-response relationship. There was no significant effect on human colon cancer, although inhibition trends disappeared in the bar chart. In order to verify the immunomodulatory effect of ZFSC, ELISA was used to analyze serums IL-2, TNF-α, and IFN in spleens. The results showed that ZFSC could enhance the immune function of tumor-bearing mice. ZFSC reduced IFN-γ and TNF-α content in the serum of HT-1080 tumor-bearing mice and inhibit PD1 and PDL1 and suggested that the antitumor mechanism of ZFSC on human fibrosarcoma could be attributed to inhibition of the PDL1/PD1 pathway

Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark of Myrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway

Shufeng Jiedu Capsules Alleviate Lipopolysaccharide-Induced Acute Lung Inflammatory Injury via Activation of GPR18 by Verbenalin

Background/Aims: Acute respiratory tract infection (ARTI) is the most common reason for outpatient physician office visits. Although powerful and significant in the treatment of infections, antibiotics used for ARTI inappropriately have been an important contributor to antibiotic resistance. We previously reported that Shufeng Jiedu Capsule (SJC) can effectively amplify anti-inflammatory signaling during infection. In this study, we aimed to systematically explore its composition and the mechanism of its effects in ARTI. Methods: Pseudomonas aeruginosa (PAK) strain was used to generate a mouse model of ARTI, which were then treated with different drugs or compounds to determine the corresponding anti-inflammatory roles. High-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry. was conducted to detect the chemical compounds in SJC. RNAs from the lung tissues of mice were prepared for microarray analysis to reveal globally altered genes and the pathways involved after SJC treatment. Results: SJC significantly inhibited the expression and secretion of inflammatory factors from PAK-induced mouse lung tissues or lipopolysaccharide-induced peritoneal macrophages. Verbenalin, one of the bioactive compounds identified in SJC, also showed notable anti-inflammatory effects. Microarray data revealed numerous differentially expressed genes among the different treatment groups; here, we focused on studying the role of GPR18. We found that the anti-inflammatory role of verbenalin was attenuated in GPR18 knockout mice compared with wild-type mice, although no statistically significant difference was observed in the untreated PAK-induced mice types. Conclusion: Our data not only showed the chemical composition of SJC, but also demonstrated that verbenalin was a significant anti-inflammatory compound, which may function through GPR18

Thoughts on the Complementation of Chinese and Western Musical Instruments and the Localization of Piano Music

At the beginning of the 20th century, Western music gradually integrated into Chinese music education institutions and various music social activities. The timbre, range and comprehensive expression of Western musical instruments have played an important role in promoting the performance of Chinese national musical instruments. At the same time, Chinese traditional music culture has also had an important impact on the localization of Western music in China, especially for the piano music

Similarity-based approach for accurately retrieving similar cases to intelligently handle online complaints

Purpose The purpose of this paper is to propose a similarity-based approach to accurately retrieve reference solutions for the intelligent handling of online complaints. Design/methodology/approach This approach uses a case-based reasoning framework and firstly formalizes existing online complaints and their solutions, new online complaints, and complaint products, problems and content as source cases, target cases and distinctive features of each case, respectively. Then the process of using existing word-level, sense-level and text-level measures to assess the similarities between complaint products, problems and contents is explained. Based on these similarities, a measure with high accuracy in assessing the overall similarity between cases is designed. The effectiveness of the approach is evaluated by numerical and empirical experiments. Findings The evaluation results show that a measure simultaneously considering the features of similarity at word, sense and text levels can obtain higher accuracy than those measures that consider only one level feature of similarity; and that the designed measure is more accurate than all of its linear combinations. Practical implications The approach offers a feasible way to reduce manual intervention in online complaint handling. Complaint products, problems and content should be synthetically considered when handling an online complaint. The designed procedure of the measure with high accuracy can be applied in other applications that consider multiple similarity features or linguistic levels. Originality/value A method for linearly combining the similarities at all linguistic levels to accurately assess the overall similarities between online complaint cases is presented. This method is experimentally verified to be helpful to improve the accuracy of online complaint case retrieval. This is the first study that considers the accuracy of the similarity measures for online complaint case retrieval. </jats:sec

Bombyx mori Dihydroorotate Dehydrogenase: Knockdown Inhibits Cell Growth and Proliferation via Inducing Cell Cycle Arrest

Dihydroorotate dehydrogenase (DHODH), in the de novo pyrimidine biosynthetic pathway, is the fourth enzyme of pyrimidine synthesis and is used to oxidize dihydroorotate and hence to orotat. We cloned and characterized here the dhod of silkworms, Bombyx mori. The full-length cDNA sequence of dhod is 1339 bp, including an open reading frame (ORF) of 1173 bp that encoded a 390 amino acid protein. And two domains were involved in the Dihydroorotate dehydrogenase amino acid sequence of silkworms, Bombyx mori (BmDHODH), namely a DHO_dh domain and a transmembrane domain in N-termina. The silkworm dhod is expressed throughout development and in nine tissues. Moreover, knockdown of the silkworm dhod gene reduced cell growth and proliferation through G2/M phase cell cycle arrest. Similarly, DHODH inhibitor (leflunomide) also reduced cell growth and proliferation, with a significant decrease of cyclin B and cdk2. DHODH is the fourth enzyme of pyrimidine synthesis, so we also found that leflunomide can inhibit, at least in part, the endomitotic DNA replication in silk glands cells. These findings demonstrate that downregulation of BmDHODH inhibits cell growth and proliferation in silkworm cells, and the endomitotic DNA replication in silk gland cells

Neural Responses to Rapid Facial Expressions of Fear and Surprise

Facial expression recognition is mediated by a distributed neural system in humans that involves multiple, bilateral regions. There are six basic facial expressions that may be recognized in humans (fear, sadness, surprise, happiness, anger, and disgust); however, fearful faces and surprised faces are easily confused in rapid presentation. The functional organization of the facial expression recognition system embodies a distinction between these two emotions, which is investigated in the present study. A core system that includes the right parahippocampal gyrus (BA 30), fusiform gyrus, and amygdala mediates the visual recognition of fear and surprise. We found that fearful faces evoked greater activity in the left precuneus, middle temporal gyrus (MTG), middle frontal gyrus, and right lingual gyrus, whereas surprised faces were associated with greater activity in the right postcentral gyrus and left posterior insula. These findings indicate the importance of common and separate mechanisms of the neural activation that underlies the recognition of fearful and surprised faces