Korea Research Institute of Bioscience and Biotechnology
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COMPOSITION FOR PREVENTING OR TREATING MUSCLE WEAKNESS DISEASES COMPRISING ALVERINE, 4-HYDROXY ALVERINE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
No full text본 발명은 알베린, 4-히드록시 알베린 또는 이들의 약학적으로 허용가능한 염을 포함하는 근력약화 관련 질환 예방 또는 치료용 약학 조성물 및 체외 근원세포의 분화 촉진용 조성물에 관한 것이다. 본 발명의 약학 조성물의 유효성분인 알베린, 4-히드록시 알베린 또는 이의 약학적으로 허용가능한 염을 근원세포에 처리할 경우, 근관세포로의 분화를 촉진시킨다. 또한, 상기 알베린, 4-히드록시 알베린 또는 이의 약학적으로 허용가능한 염을 마우스에 처리할 경우, 마우스의 근육량을 증가시키며, 근력을 향상시킬 수 있다. 따라서, 본 발명에 따른 약학 조성물은 근원세포의 분화 촉진 및 근력약화 관련 질환의 예방 또는 치료에 유용하게 사용될 수 있다.국
Cyclic peptide mimotopes for the detection of serum anti-ATIC autoantibody biomarker in hepato-cellular carcinoma
No full textTumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.
Coronary circulatory indexes in non-infarct-related vascular territories in a porcine acute myocardial infarction model
No full textObjectives: The aim of this study was to evaluate temporal changes in coronary hemodynamic and physiological indexes in the non-infarct-related artery (IRA), which might be affected by adjacent infarcted myocardium, using an experimental animal model of acute myocardial infarction. Background: There has been debate on the reliability of fractional flow reserve and resting pressure-derived indexes, including instantaneous wave-free ratio, in the non-IRA in patients with acute ST-segment elevation myocardial infarction. Methods: In Yorkshire swine, acute myocardial infarction was simulated with selective balloon occlusion at the left circumflex coronary artery as the IRA for 30 min. Non-IRA stenosis was created using bare-metal stent implantation in the left anterior descending coronary artery 4 weeks before the experiments. Serial changes in systemic hemodynamic status, coronary pressure, and Doppler-derived coronary flow velocity were measured in a nonoccluded left anterior descending coronary artery as the non-IRA from baseline, balloon occlusion of the left circumflex coronary artery, and 15 min after reperfusion of the left circumflex coronary artery. Results: Among the 6 experimental subjects, the median diameter stenosis of the non-IRA was 33.9% (interquartile range: 21.7% to 46.1%). During balloon occlusion of the IRA, there were transient significant changes in both resting and hyperemic aortic pressure, distal coronary pressure, averaged peak velocity, transstenotic pressure gradient, and microvascular resistance of the non-IRA (p < 0.020 for all). After reperfusion of the IRA, the resting averaged peak velocity (p = 0.002) and resting transstenotic pressure gradient (p = 0.004) were significantly increased and resting microvascular resistance (p = 0.004) was significantly decreased compared with their values in the baseline phase. However, the hyperemic averaged peak velocity (p = 0.479), hyperemic transstenotic pressure gradient (p = 0.778), and hyperemic microvascular resistance (p = 0.816) were not significantly different compared with those in the baseline phase. After reperfusion, fractional flow reserve in the non-IRA was not significantly different (0.94 ± 0.01 vs. 0.93 ± 0.01; p = 0.353), while coronary flow reserve (1.93 ± 0.07 vs. 1.36 ± 0.07; p = 0.025) and instantaneous wave-free ratio (0.97 ± 0.01 vs. 0.93 ± 0.01; p = 0.001) were significantly lower than baseline values. Conclusions: In a porcine model of acute myocardial infarction, occlusion of the IRA induced significant changes in systemic hemodynamic status and coronary circulatory indexes of the non-IRA. However, after reperfusion of the IRA, fractional flow reserve did not change significantly, whereas coronary flow reserve and instantaneous wave-free ratio showed significant changes compared with baseline values.
A designed whole-cell biosensor for live diagnosis of gut inflammation through nitrate sensing
No full textMicrobes reprogrammed using advanced genetic circuits are envisaged as emerging living diagnostics for a wide range of diseases and play key roles in regulating gut microbiota to treat disease-associated symptoms in a non-invasive manner. Here, we developed a designer probiotic Escherichia coli that senses and responds to nitrate, a biomarker of gut inflammation. To this end, we first employed the NarX-NarL two-component regulatory system in E. coli to construct a nitrate-responsive genetic circuit. Next, we optimized the nitrate biosensor for the best performance using measures of sensitivity and specificity. We then introduced this genetic circuit into a probiotic E. coli Nissle 1917. We demonstrated that the designed biosensor can sense elevated nitrate levels during gut inflammation in mice with native gut microbiota. Moreover, using Boolean AND gate, we generated a genetically encoded biosensor for simultaneous sensing of the thiosulfate and nitrate biomarkers, thus increasing the tool's specificity for diagnosing gut inflammation. The nitrate-responsive genetic circuit will enable new approaches for non-invasive diagnostics of inflammation-associated diseases.
Enhancement of target specificity of CRISPR-Cas12a by using a chimeric DNA-RNA guide
No full textThe CRISPR-Cas9 system is widely used for target-specific genome engineering. CRISPR-Cas12a (Cpf1) is one of the CRISPR effectors that controls target genes by recognizing thymine-rich protospacer adjacent motif (PAM) sequences. Cas12a has a higher sensitivity to mismatches in the guide RNA than does Cas9; therefore, off-target sequence recognition and cleavage are lower. However, it tolerates mismatches in regions distant from the PAM sequence (TTTN or TTN) in the protospacer, and off-target cleavage issues may become more problematic when Cas12a activity is improved for therapeutic purposes. Therefore, we investigated off-target cleavage by Cas12a and modified the Cas12a (cr)RNA to address the off-target cleavage issue. We developed a CRISPR-Cas12a that can induce mutations in target DNA sequences in a highly specific and effective manner by partially substituting the (cr)RNA with DNA to change the energy potential of base pairing to the target DNA. A model to explain how chimeric (cr)RNA guided CRISPR-Cas12a and SpCas9 nickase effectively work in the intracellular genome is suggested. Chimeric guide-based CRISPR- Cas12a genome editing with reduced off-target cleavage, and the resultant, increased safety has potential for therapeutic applications in incurable diseases caused by genetic mutations.
Anti-inflammatory role of Prunus persica L. Batsch methanol extract on lipopolysaccharide-stimulated glial cells
No full textGlial cells are the resident immune cells of the central nervous system. Reactive glial cells release inflammatory mediators that induce neurotoxicity or aggravate neurodegeneration. regulation of glial activation is crucial for the initiation and progression of neuropathological conditions. constituents of the peach tree (Prunus persica l. Batsch), which has a global distribution, have been found to exert therapeutic effects in pathological conditions, such as rashes, eczema and allergies. However, the therapeutic potential of its aerial parts (leaves, fruits and twigs) remains to be elucidated. The present study aimed to evaluate the anti-inflammatory role of P. persica methanol extract (PPB) on lipopolysaccharide (LPS).stimulated glial cells. High.performance liquid chromatography coupled with tandem mass spectrometry analysis showed that PPB contained chlorogenic acid and catechin, which have antioxidant properties. Western blot and reverse transcription polymerase chain reaction results indicated that PPB reduced the transcription of various proinflammatory enzymes (nitric oxide synthase and cyclooxygenase.2) and cytokines [tumor necrosis factor. , interleukin (IL ).1 and IL. 6] in LPS.stimulated BV2 cells. In addition, PPB inhibited the activation of NF. B and various mitogen.activated protein kinases required for proinflammatory mediator transcription. Finally, nitrite measurement and immunocytochemistry results indicated that PPB also suppressed nitrite production and NF. B translocation in LPS.stimulated primary astrocytes. Thus, PPB may be used as a potential therapeutic agent for neurodegenerative diseases and neurotoxicity via the suppression of glial cell activation. ⓒ This work is licensed under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) License.
Anti-allergy effect of mojabanchromanol isolated from Sargassum horneri in bone marrow-derived cultured mast cells
No full textThis study was conducted to isolate and identify an active compound possessing anti-allergic property from the Jeju Island inhabiting Sargassum horneri (S. horneri). The ethanol extract of S. horneri (SHE) exhibited an anti-allergic effect via the reduction of β-hexosaminidase release in immunoglobulin E (IgE)/bovine serum albumin (BSA)-stimulated bone marrow-derived cultured mast cells (BMCMCs). SHE was subjected to liquid phase fractionation obtaining the hexane fraction, and this was further purified via ODS column chromatography and prep-C18 HPLC. The isolated compound was identified as mojabanchromanol (MC) by 1H, 13C NMR, and LCMS analysis. Isolated MC showed a higher inhibitory effect on the β-hexosaminidase release than those of SHE without cytotoxicity. Moreover, MC inhibited the mRNA expression levels of allergic cytokines in BMCMCs. This is the first report to inform on the anti-allergic property of MC isolated from S. horneri. In conclusion, SHE, as well as MC, is applicable in the development of functional health food, cosmetics, and pharmaceutical products exhibiting anti-allergic effects.
What we know and what we need to know about adenovirus 36-induced obesity
No full textBackground: Many internal and external factors are related to obesity. Pathogens that can induce obesity are the most interesting external factors. While the relationship between pathogenic human intestinal microbiota and obesity has been extensively studied, viruses have received relatively little attention. Among the human obesity-related viruses, adenovirus 36 (Ad36) is most commonly associated with obesity.
Methods: A literature search was conducted using the articles in the PubMed database published from April 1982 to April 2019. The following main keywords were used: ('adenovirus 36') and ('obesity') and ('cellular mechanism' or 'genetic factor' or 'immune response' or 'inflammation').
Results: In this review, we have discussed the known facts and what requires to be understood regarding Ad36-induced obesity. In particular, we have summarized the cellular mechanism of Ad36-induced obesity, as well as the genetic and immunological factors affected by Ad36 infection. Ad36 infection increases adipogenesis in animals and humans. Ad36-induced inflammation contributes to angiogenesis in adipose tissues, thereby maintaining proper glycemic control and metabolic robustness. The E4orf1 protein derived from Ad36 is responsible for increasing glucose uptake due to the translocation of GLUT4 via the Ras-PI3K pathway, which is involved in 'distal' insulin signaling.
Conclusions: We expect that this review will assist in guiding future investigations regarding Ad36-induced obesity. (1) Identification of the direct and indirect factors affecting Ad36-induced obesity and understanding their mechanism of action and (2) utilization of the Ad36-induced improvement in glycemic control for clinical applications, with efforts toward developing E4orf1-based drugs.
RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells
No full textIn this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n？=？3) and Prx II knockout DMSCs (n？=？3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p？≤？0.05) between the PrxII+/+ (WT) and PrxII？/？ sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII？/？ samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII？/？ vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.