Korea Research Institute of Bioscience and Biotechnology
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Bioinformatics analysis of evolution and human disease related transposable element-derived microRNAs
No full textTransposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of 19 to 24 nucleotides and numerous miRNAs are derived from TE. In this study, to support general knowledge on TE and miRNAs derived from TE, several bioinformatics tools and databases were used to analyze miRNAs derived from TE in two aspects: evolution and human disease. The distribution of TEs in diverse species presents that almost half of the genome is covered with TE in mammalians and less than a half in other vertebrates and invertebrates. Based on selected evolution-related miRNAs studies, a total of 51 miRNAs derived from TE were found and analyzed. For the human disease-related miRNAs, total of 34 miRNAs derived from TE were organized from the previous studies. In summary, abundant miRNAs derived from TE are found, however, the function of miRNAs derived from TE is not informed either. Therefore, this study provides theoretical understanding of miRNAs derived from TE by using various bioinformatics tools.
AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-β signaling pathway
No full textAsthma is characterized by airway hyperresponsiveness and allergic inflammation, detrimentally affecting the patients’ quality of life. The development of new drugs for the treatment of asthma is warranted to alleviate these issues. Recent studies have demonstrated that sirtuin2 (SIRT2) aggravates asthmatic inflammation by up-regulation of T-helper type 2 responses and macrophage polarization. However, effects of SIRT2 on mast cell activation remain obscure. In this study, we investigated the effects of AGK2, an inhibitor for SIRT2, on mast cell-mediated allergic airway inflammation. Pre-treatment with AGK2 inhibited degranulation of mast cells by suppressing the FcεRI signaling pathway and intracellular calcium influx. The expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-5, IL-6, and IL-8, was inhibited via regulation of transcription factors such as NF-κB and NRF2. These effects of AGK2 were verified in passive cutaneous anaphylaxis and acute lung injury animal models. AGK2 attenuated Evans blue pigmentation by inhibiting mast cell activation and lung barrier dysfunction by inhibiting inflammatory responses in these animal models. In the ovalbumin (OVA)-induced allergic airway inflammation murine model, AGK2 alleviated allergic asthma symptoms such as lung histological changes (immune cell and mast cell infiltration, collagen deposition, and α-smooth muscle actin expression) and serum immunoglobulins (Ig) levels (IgE, OVA-specific IgE, IgG1, and IgG2a). Moreover, AGK2 reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-4, IL-5, and IL-6) and inflammatory mediators (myeloperoxidase, eosinophil peroxidase, and tumor growth factor-α) in the bronchoalveolar lavage fluid and lung tissues. In addition, the anti-fibrotic effects of AGK2 were verified using lung epithelial cells and TGF-β/Smad reporter stable cells. In conclusion, our findings suggest that SIRT2 plays a role in mast cell-mediated airway inflammatory disease. Therefore, AGK2 is a good potential candidate for treating allergic asthma and lung inflammation.
Identification of a second type of AHL-lactonase from Rhodococcus sp. BH4, belonging to the α/β hydrolase superfamily
No full textN-acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) plays a major role in development of biofilms, which contribute to rise in infections and biofouling in water-related industries. Interference in QS, called quorum quenching (QQ), has recieved a lot of attention in recent years. Rhodococcus spp. are known to have prominent quorum quenching activity and in previous reports it was suggested that this genus possesses multiple QQ enzymes, but only one gene, qsdA, which encodes an AHL-lactonase belonging to phosphotriesterase family, has been identified. Therefore, we conducted a whole genome sequencing and analysis of Rhodococcus sp. BH4 isolated from a wastewater treatment plant. The sequencing revealed another gene encoding a QQ enzyme (named jydB) that exhibited a high AHL degrading activity. This QQ enzyme had a 46% amino acid sequence similarity with the AHL-lactonase (AidH) of Ochrobactrum sp. T63. HPLC analysis and AHL restoration experiments by acidification revealed that the jydB gene encodes an AHL-lactonase which shares the known characteristics of the α/β hydrolase family. Purified recombinant JydB demonstrated a high hydrolytic activity against various AHLs. Kinetic analysis of JydB revealed a high catalytic efficiency (kcat/KM) against C4-HSL and 3-oxo-C6 HSL, ranging from 1.88 × 106 to 1.45 × 106 M-1 s-1, with distinctly low KM values (0.16 - 0.24 mM). This study affirms that the AHL degrading activity and biofilm inhibition ability of Rhodococcus sp. BH4 may be due to the presence of multiple quorum quenching enzymes, including two types of AHL-lactonases, in addition to AHL-acylase and oxidoreductase, for which the genes have yet to be described.
Peroxisome metabolism in cancer
No full textPeroxisomes are metabolic organelles involved in lipid metabolism and cellular redox balance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acid synthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations in peroxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linked to metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-related disorders, revealing the significance of peroxisome metabolism in human health. Cancer is a disease with metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functional eects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles, such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated than it is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomes and the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential of inactivating peroxisomes to target cancer metabolism, which may pave the way for more eective cancer treatment.
Nanoformulated single-stranded RNA-based adjuvant with a coordinative amphiphile as an effective stabilizer: inducing humoral immune response by activation of antigen-presenting cells
No full textAs agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.
Miconazole inhibits signal transducer and activator of transcription 3 signaling by preventing its interaction with DNA damage-induced apoptosis suppressor
No full textDNA damage-induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) via their interaction. Here, we identified miconazole as an inhibitor of DDIAS/STAT3 interaction by screening a chemical library using a yeast two-hybrid assay. Miconazole inhibited growth, migration and invasion of lung cancer cells. Furthermore, miconazole suppressed STAT3 tyrosine Y705 phosphorylation and the expression of its target genes, such as cyclin D1, survivin and snail but had no suppressive effect on the activation of ERK1/2 or AKT, which is involved in the survival of lung cancer. As expected, no interaction between DDIAS and STAT3 occurred in the presence of miconazole, as confirmed by immunoprecipitation assays. Mouse xenograft experiments showed that miconazole significantly suppressed both tumor size and weight in an NCI-H1703 mouse model. Tyrosine phosphorylation of STAT3 at Y705 and expression of its targets, such as cyclin D1, survivin and snail, were decreased in miconazole-treated tumor tissues, as compared with those in vehicle-treated tumor tissues. These data suggest that miconazole exerts an anti-cancer effect by suppressing STAT3 activation through inhibiting DDIAS/STAT3 binding.
Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans
No full textMcrA is a key transcription factor that functions as a global repressor of fungal secondary metabolism in Aspergillus species. Here, we report that mcrA is one of the VosA-VelB target genes and McrA governs the cellular and metabolic development in Aspergillus nidulans. The deletion of mcrA resulted in a reduced number of conidia and decreased mRNA levels of brlA, the key asexual developmental activator. In addition, the absence of mcrA led to a loss of long-term viability of asexual spores (conidia), which is likely associated with the lack of conidial trehalose and increased β-(1,3)-glucan levels in conidia. In supporting its repressive role, the mcrA deletion mutant conidia contain more amounts of sterigmatocystin and an unknown metabolite than the wild type conidia. While overexpression of mcrA caused the fluffy-autolytic phenotype coupled with accelerated cell death, deletion of mcrA did not fully suppress the developmental defects caused by the lack of the regulator of G-protein signaling protein FlbA. On the contrary to the cellular development, sterigmatocystin production was restored in the ΔflbA ΔmcrA double mutant, and overexpression of mcrA completely blocked the production of sterigmatocystin. Overall, McrA plays a multiple role in governing growth, development, spore viability, and secondary metabolism in A. nidulans.
Morphological and phylogenetic data do not support the split of Alexandrium into four genera
No full textA recently published study analyzed the phylogenetic relationship between the genera Centrodinium and Alexandrium, confirming an earlier publication showing the genus Alexandrium as paraphyletic. This most recent manuscript retained the genus Alexandrium, introduced a new genus Episemicolon, resurrected two genera, Gessnerium and Protogonyaulax, and stated that: “The polyphyly [sic] of Alexandrium is solved with the split into four genera”. However, these reintroduced taxa were not based on monophyletic groups. Therefore this work, if accepted, would result in replacing a single paraphyletic taxon with several non-monophyletic ones. The morphological data presented for genus characterization also do not convincingly support taxa delimitations. The combination of weak molecular phylogenetics and the lack of diagnostic traits (i.e., autapomorphies) render the applicability of the concept of limited use. The proposal to split the genus Alexandrium on the basis of our current knowledge is rejected herein. The aim here is not to present an alternative analysis and revision, but to maintain Alexandrium. A better constructed and more phylogenetically accurate revision can and should wait until more complete evidence becomes available and there is a strong reason to revise the genus Alexandrium. The reasons are explained in detail by a review of the available molecular and morphological data for species of the genera Alexandrium and Centrodinium. In addition, cyst morphology and chemotaxonomy are discussed, and the need for integrative taxonomy is highlighted.
Effects of graphene oxide-gold nanoparticles nanocomposite on highly sensitive foot-and-mouth disease virus detection
No full textThe polymerase chain reaction (PCR) has become a powerful molecular diagnostic technique over the past few decades, but remains somewhat impaired due to low specificity, poor sensitivity, and false positive results. Metal and carbon nanomaterials, quantum dots, and metal oxides, can improve the quality and productivity of PCR assays. Here, we describe the ability of PCR assisted with nanomaterials (nano-PCR) comprising a nanocomposite of graphene oxide (GO) and gold nanoparticles (AuNPs) for sensitive detection of the foot-and-mouth disease virus (FMDV). Graphene oxide and AuNPs have been widely applied as biomedical materials for diagnosis, therapy, and drug delivery due to their unique chemical and physical properties. Foot-and-mouth disease (FMD) is highly contagious and fatal for cloven-hoofed animals including pigs, and it can thus seriously damage the swine industry. Therefore, a highly sensitive, specific, and practical method is needed to detect FMDV. The detection limit of real-time PCR improved by ~1000 fold when assisted by GO-AuNPs. We also designed a system of detecting serotypes in a single assay based on melting temperatures. Our sensitive and specific nano-PCR system can be applied to diagnose early FMDV infection, and thus may prove to be useful for clinical and biomedical applications.
Morphology, ultrastructure, and molecular phylogeny of the unarmoured dinoflagellate Kirithra sigma sp. nov. (Ceratoperidiniaceae, Dinophyceae)
No full textA Gymnodinium-like dinoflagellate, Kirithra sigma sp. nov., was isolated from Jiaozhou Bay, China, and the southern coast of Korea, and examined by light, scanning, and transmission electron microscopy. Pigment composition and nuclear-encoded partial large subunit ribosomal RNA (LSU rRNA) gene were determined. Cells were oval-shaped (26.4？36.4 μm long and 17.7？27.2 μm wide), with a conical epicone and hemispherical hypocone. Its cingulum and sulcus were deep and wide. The cingulum encircled the cell completely, its ends slightly overlapping and displaced one to two cingular widths; the sulcus and sulcal extension formed a sigmoid curve. The anterior sulcal extension contacted the apical structure complex (ASC). The ASC formed a complete circle, consisting of three parallel series of vesicles, and the amphiesmal vesicles within ASC were arranged with one central vesicle (sometimes two) encircled by approximately three rows of polygonal amphiesmal vesicles. Polygonal amphiesmal vesicles of different sizes covered the whole cell surface. The subspherical nucleus was located in the hypocone. Pigment analysis showed that peridinin was the main accessory pigment. The present species is morphologically similar to Kirithra asteri but differs in numbers and rows of amphiesmal vesicles within the ASC, absence of ventral pore, and a sigmoid curve formed by the sulcus and sulcal extension. The partial LSU rRNA gene sequence (c. 1400 bases) of K. sigma differed by c. 5.3% from that of K. asteri. Molecular phylogeny revealed that K. sigma formed an independent sister clade to K. asteri, indicating they are congeneric but different species.