HtrA2 interacts with A beta peptide but does not directly alter its production or degradation.

Liu, Meng-Lu,Liu, Ming-Jie,Kim, Jin-Man,Kim, Hyeon-Jin,Kim, Jeong-Hak,Hong, Seong-Tshool Korean Society for Molecular Biology 2005 Molecules and cells Vol.20 No.1

<P>HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosis-inducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with A beta peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of A beta peptide. The interaction between A beta peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in A beta peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of A beta peptide at the beta/gamma-secretase level, or the degradation of A beta peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of A beta40 and A beta42 by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer's disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of A beta40 and A beta42 suggests that it may play some positive role in mammalian cells.</P>

Omi is a mammalian heat-shock protein that selectively binds and detoxifies oligomeric amyloid-beta.

Liu, Meng-Lu,Liu, Ming-Jie,Shen, Yan-Fei,Ryu, Hoon,Kim, Hyeon-Jin,Klupsch, Kristina,Downward, Julian,Hong, Seong-Tshool Cambridge University Press 2009 Journal of cell science Vol.122 No.11

<P>The cellular generation of toxic metabolites and subsequent detoxification failure can cause the uncontrolled accumulation of these metabolites in cells, leading to cellular dysfunction. Amyloid-beta protein (Abeta), a normal metabolite of neurons, tends to form toxic oligomeric structures that cause neurodegeneration. It is unclear how healthy neurons control the levels of intracellular oligomeric Abeta in order to avoid neurodegeneration. Using immunochemical and biochemical studies, we show that the Abeta-binding serine protease Omi is a stress-relieving heat-shock protein that protects neurons against neurotoxic oligomeric Abeta. Through its PDZ domain, Omi binds preferentially to neurotoxic oligomeric forms of Abeta rather than non-toxic monomeric forms to detoxify oligomeric Abeta by disaggregation. This specific interaction leads not only to mutual detoxification of the pro-apoptotic activity of Omi and Abeta-induced neurotoxicity, but also to a reduction of neurotoxic-Abeta accumulation. The neuroprotective role of Omi is further supported by its upregulation during normal neurogenesis and neuronal maturation in mice, which could be in response to the increase in the generation of oligomeric Abeta during these processes. These findings provide novel and important insights into the detoxification pathway of intraneuronal oligomeric Abeta in mammals and the protective roles of Omi in neurodegeneration, suggesting a novel therapeutic target in neurodegenerative diseases.</P>

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway

Zhou Meng-jiao,Yang Jia-jie,Ma Ting-yao,Feng Ge-xuan,Wang Xue-lian,Wang Li-Yong,Ge Yu-ze,Gao Ran,Hong-liang Liu,Shan Lin,Kong Lu,Chen Xiao-hong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the “MYC_TARGETS_V2” gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the “MYC_TARGETS_V2” gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

Analysis of the Genome Sequence of Strain GiC-126 of Gloeostereum incarnatum with Genetic Linkage Map

( Wan-zhu Jiang ),( Fang-jie Yao ),( Ming Fang ),( Li-xin Lu ),( You-min Zhang ),( Peng Wang ),( Jing-jing Meng ),( Jia Lu ),( Xiao-xu Ma ),( Qi He ),( Kai-sheng Shao ),( Asif Ali Khan ),( Yun-hui Wei 한국균학회 2021 Mycobiology Vol.49 No.4

Gloeostereum incarnatum has edible and medicinal value and was first cultivated and domesticated in China. We sequenced the G. incarnatum monokaryotic strain GiC-126 on an Illumina HiSeq X Ten system and obtained a 34.52-Mb genome assembly sequence that encoded 16,895 predicted genes. We combined the GiC-126 genome with the published genome of G. incarnatum strain CCMJ2665 to construct a genetic linkage map (GiC-126 genome) that had 10 linkage groups (LGs), and the 15 assembly sequences of CCMJ2665 were integrated into 8 LGs. We identified 1912 simple sequence repeat (SSR) loci and detected 700 genes containing 768 SSRs in the genome; 65 and 100 of them were annotated with gene ontology (GO) terms and KEGG pathways, respectively. Carbohydrate-active enzymes (CAZymes) were identified in 20 fungal genomes and annotated; among them, 144 CAZymes were annotated in the GiC-126 genome. The A mating-type locus (MAT-A) of G. incarnatum was located on scaffold885 at 38.9 cM of LG1 and was flanked by two homeodomain (HD1) genes, mip and beta-fg. Fourteen segregation distortion markers were detected in the genetic linkage map, all of which were skewed toward the parent GiC-126. They formed three segregation distortion regions (SDR1-SDR3), and 22 predictive genes were found in scaffold1920 where three segregation distortion markers were located in SDR1. In this study, we corrected and updated the genomic information of G. incarnatum. Our results will provide a theoretical basis for fine gene mapping, functional gene cloning, and genetic breeding the follow-up of G. incarnatum.

Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve in Patients with Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus

Chun Xiang Tang,Meng Jie Lu,Joseph Uwe Schoepf,Christian Tesche,Maximilian Bauer,John Nance,Parkwood Griffith,Guang Ming Lu,Long Jiang Zhang 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.2

Objective: To examine the fractional flow reserve derived from computed tomographic angiography (CT-FFR) in patients with anomalous origin of the right coronary artery from the left coronary sinus (R-ACAOS) with an interarterial course, assess the relationship of CT-FFR with the anatomical features of interarterial R-ACAOS on coronary computed tomographic angiography (CCTA), and determine its clinical relevance. Materials and Methods: Ninety-four patients with interarterial R-ACAOS undergoing CCTA were retrospectively included. Anatomic features (proximal vessel morphology [oval or slit-like], take-off angle, take-off level [below or above the pulmonary valve], take-off type, intramural course, % proximal narrowing area, length of narrowing, minimum luminal area [MLA] at systole and diastole, and vessel compression index) on CCTA associated with CT-FFR ≤ 0.80 were analyzed. Receiver operating characteristic analysis was performed to describe the diagnostic performance of CT-FFR ≤ 0.80 in detecting interarterial R-ACAOS. Results: Significant differences were found in proximal vessel morphology, take-off level, intramural course, % proximal narrowing area, and MLA at diastole (all p < 0.05) between the normal and abnormal CT-FFR groups. Take-off level, intramural course, and slit-like ostium (all p < 0.05) predicted hemodynamic abnormality (CT-FFR ≤ 0.80) with accuracies of 0.69, 0.71, and 0.81, respectively. Patients with CT-FFR ≤ 0.80 had a higher prevalence of typical angina (29.4% vs. 7.8%, p = 0.025) and atypical angina (29.4% vs. 6.5%, p = 0.016). Conclusion: Take-off level, intramural course, and slit-like ostium were the main predictors of abnormal CT-FFR values. Importantly, patients with abnormal CT-FFR values showed a higher prevalence of typical angina and atypical angina, indicating that CT-FFR is a potential tool to gauge the clinical relevance in patients with interarterial R-ACAOS.

HtrA2 Interacts with Aβ Peptide but Does Not Directly Alter Its Production or Degradation

Seong-Tshool Hong,Meng-Lu Liu,Ming-Jie Liu,Jin-Man Kim,Hyeon-Jin Kim,Jeong-Hak Kim 한국분자세포생물학회 2005 Molecules and cells Vol.20 No.1

HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosisinducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with Aβ peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of β peptide. The interaction between Aβ peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in Aβ peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of Aβ peptide at the β/γ-secretase level, or the degradation of Aβ peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of Aβ40 and Aβ42 by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer’s disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of Aβ40 and Aβ42 suggests that it may play some positive role in mammalian cells.

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.

Enhancing cationic lipid-mediated tranfection efficiency of NT2/D1 cells

심안비 ( Yan Fei Shen ),류명걸 ( Ming Jie Liu ),유맹루 ( Meng Lu Liu ),유양 ( Yang Yu ),이연식 ( Youn Sik Lee ),홍성출 ( Seong Tshool Hong ) 전북대학교 의과학연구소 2007 全北醫大論文集 Vol.31 No.2

Cationic lipids, such as lipofectamine series, are the most well developed nonviral vectors that widely used to transfect nucleic acids into eukaryotic cells. Although cationic lipids are known as safer carriers, their transfection efficiency remains low in certain cell lines, such as NT2/D1. In this study, we developed an efficient method which mix the lipofectamine 2000/plasmid pEGFP-N1 lipoplex with trypsin treated NT2/D1 cells in small volume for 1 minute to improve the transfection efficiency. Transfection efficiency of NT2/D1 was significantly increased by this method up to 90% without visible toxicity and expression of transfected pEGFP-N1 plasmid was 2.6-fold increased than using conventional method.

Genetic linkage map construction and quantitative trait loci mapping of agronomic traits in Gloeostereum incarnatum

Jiang Wan-Zhu,Yao Fang-Jie,Lu Li-Xin,Fang Ming,Wang Peng,Zhang You-Min,Meng Jing-Jing,Lu Jia,Ma Xiao-Xu,He Qi,Shao Kai-Sheng 한국미생물학회 2021 The journal of microbiology Vol.59 No.1

Gloeostereum incarnatum is an edible medicinal mushroom widely grown in China. Using the whole genome of G. incarnatum, simple sequence repeat (SSR) markers were developed and synthetic primers were designed to construct its first genetic linkage map. The 1,048.6 cm map is composed of 10 linkage groups and contains 183 SSR markers. In total, 112 genome assembly sequences were anchored, representing 16.43 Mb and covering 46.41% of the genome. Selfing populations were used for quantitative trait loci (QTL) targeting, and the composite interval mapping method was used to co-localize the mycelium growth rate (potato dextrose agar and sawdust), growth period, yield and fruiting body length, and width and thickness. The 14 QTLs of agronomic traits had LOD values of 3.20–6.51 and contribution rates of 2.22– 13.18%. No linkage relationship was found between the mycelium growth rate and the growth period, but a linkage relationship was observed among the length, width and thickness of the fruiting bodies. Using NCBI’s BLAST alignment, the genomic sequences corresponding to the QTL regions were compared, and a TPR-like protein candidate gene was selected. Using whole-genome data, 138 candidate genes were found in four sequence fragments of two SSR markers located in the same scaffold. The genetic map and QTLs established in this study will aid in developing selective markers for agronomic traits and identifying corresponding genes, thereby providing a scientific basis for the further gene mapping of quantitative traits and the marker-assisted selection of functional genes in G. incarnatum breeding programs.

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Yuan Na,Li Xiaoyan,Wang Meng,Zhang Zhilin,Qiao Lu,Gao Yamei,Xu Xinjian,Zhi Jie,Li Yang,Li Zhongxin,Jia Yitao 거트앤리버 소화기연관학회협의회 2022 Gut and Liver Vol.16 No.4

Background/Aims:This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions: An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.