Korea Research Institute of Bioscience and Biotechnology
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Viburnum stellato？tomentosum extract suppresses obesity and hyperglycemia through regulation of lipid metabolism in high？fat diet？fed mice
No full textThe potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid β-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid β-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.
Downregulation of swpa4 peroxidase expression in transgenic sweetpotato plants decreases abiotic stress tolerance and reduces stress-related peroxidase expression
No full textClass III peroxidases are involved in plant responses to various environmental conditions. Peroxidase production is triggered by various stimuli and activates stress-related signaling pathways to help plants cope with abiotic and biotic stresses. Recent evidence suggests that the interplay between diverse peroxidases plays a critical role in regulating stress responses. However, the underlying molecular mechanisms remain poorly understood. Previous research showed that transgenic sweetpotato overexpressing the swpa4 peroxidase gene exhibited increased tolerance to oxidative stress and high salinity. In this study, loss of function of the swpa4 peroxidase gene in sweetpotato was assessed in transgenic plants with constitutive RNAi-mediated suppression of the swpa4 gene. Compared with control plants, leaf discs from RNAi-suppressed lines exhibited increased damage following treatment with the oxidative stressors hydrogen peroxide and methyl viologen. Transgenic plants also showed reduced resistance to high salinity conditions compared with control plants. Repression of swpa4 also led to reduced expression of the endogenous stress-related peroxidase genes swpa1, swpa2, and swpn1. These findings suggest that swpa4 regulates signaling pathways involved in the regulation of peroxidase metabolism during the stress response in sweetpotato.
TMEM52B suppression promotes cancer cell survival and invasion through modulating E-cadherin stability and EGFR activity
No full textBackground: TMEM52B is a novel gene broadly expressed in a variety of normal human tissues. However, the biological function of TMEM52B expression in cancer is largely unknown.
Methods: The effects of TMEM52B on tumor growth and metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. Clinical datasets from KmPlotter and The Cancer Genome Atlas (TCGA) were analyzed in relation to TMEM52B expression and function.
Results: Suppression of TMEM52B in colon cancer cells promoted cancer cell epithelial-mesenchymal transition (EMT), invasion, and survival in vitro. Similarly, in vivo studies showed increased tumor growth and circulating tumor cell survival (early metastasis). ERK1/2, JNK, and AKT signaling pathways were involved in TMEM52B suppression-induced invasiveness and cell survival. TMEM52B suppression promoted activation and internalization of epidermal growth factor receptor (EGFR) with enhanced downstream signaling activity, leading to enhanced cell survival and invasion. In addition, TMEM52B suppression reduced E-cadherin stability, likely due to a reduced association between it and E-cadherin, which led to enhanced β-catenin transcriptional activity. Concomitantly, TMEM52B suppression promoted generation of soluble E-cadherin fragments, contributing to the activation of EGFR. Clinical data showed that high TMEM52B expression correlated with increased patient survival in multiple types of cancer, including breast, lung, kidney, and rectal cancers, and suggested a correlation between TMEM52B and E-cadherin.
Conclusions: These findings suggest that TMEM52B is a novel modulator of the interplay between E-cadherin and EGFR. It is possible that TMEM52B functions as a tumor-suppressor that could potentially be used as a novel prognostic marker for cancer.
Induction of autophagy protects against extreme hypoxia-induced damage in porcine embryo
No full textIn the mammalian female reproductive tract, physiological oxygen tension is lower than that of the atmosphere. Therefore, to mimic in vivo conditions during in vitro culture (IVC) of mammalian early embryos, 5% oxygen has been extensively used instead of 20%. However, the potential effect of hypoxia on the yield of early embryos with high developmental competence remains unknown or controversial, especially in pigs. In the present study, we examined the effects of low oxygen tension under different oxygen tension levels on early developmental competence of parthenogenetically activated (PA) and in vitro-fertilized (IVF) porcine embryos. Unlike the 5% and 20% oxygen groups, exposure of PA embryos to 1% oxygen tension, especially in early-phase IVC (0？2 days), greatly decreased several developmental competence parameters including blastocyst formation rate, blastocyst size, total cell number, inner cell mass (ICM) to trophectoderm (TE) ratio, and cellular survival rate. In contrast, 1% oxygen tension did not affect developmental parameters during the middle (2？4 days) and late phases (4？6 days) of IVC. Interestingly, induction of autophagy by rapamycin treatment markedly restored the developmental parameters of PA and IVF embryos cultured with 1% oxygen tension during early-phase IVC, to meet the levels of the other groups. Together, these results suggest that the early development of porcine embryos depends on crosstalk between oxygen tension and autophagy. Future studies of this relationship should explore the developmental events governing early embryonic development to produce embryos with high developmental competence in vitro.
Hydrodynamic cavitation for bacterial disinfection and medium recycling for sustainable Ettlia sp. cultivation
No full textOpen cultivation systems are the most economic option for microalgal biomass production but their harvesting cost, bacterial invasion, and water usage are still deterring large-scale applications. Therefore, in this study, low-cost techniques for harvesting, bacterial disinfection, and medium recycling were sequentially implemented for Ettlia sp. For harvesting, the employed auto-flocculation harvested 96% of algae but was not able to remove bacteria that invaded during cultivation. For this reason, hydrodynamic treatment was applied as a bacterial disinfection method for medium recycling, and treated up to 100% of the bacteria in the supernatant. Afterward, the supernatant was replenished with nutrients and reused to grow microalgae. In medium-recycled cultivation, auto-flocculation recycled (AR) medium showed the highest final biomass concentration of 3.84 g L？1, while the centrifugation recycled (CR) medium and the fresh medium (FM) resulted in 3.78 and 3.67 g L？1, respectively. In addition, the lipid content of the AR group was highly increased to 20.4%, resulting in the highest lipid productivity of 0.11 g L？1 d？1. Moreover, an analysis of fatty acid methyl ester compositions confirmed that 76.6% of lipid from the AR group were mainly composed of C16-C18, which are suitable for biodiesel. Consequently, the results showed that the implementation of low-cost techniques not only reduced process costs and water usage but also enhances both the biomass and lipid productivities of the species.
Global proteomics to study silica nanoparticle-induced cytotoxicity and is mechanisms in HepG2 cells
No full textSilica nanoparticles (SiO2 NPs) are commonly used in medical and pharmaceutical fields. Research into the cytotoxicity and overall proteomic changes occurring during initial exposure to SiO2 NPs is limited. We investigated the mechanism of toxicity in human liver cells according to exposure time [0, 4, 10, and 16 h (h)] to SiO2 NPs through proteomic analysis using mass spectrometry. SiO2 NP-induced cytotoxicity through various pathways in HepG2 cells. Interestingly, when cells were exposed to SiO2 NPs for 4 h, the morphology of the cells remained intact, while the expression of proteins involved in mRNA splicing, cell cycle, and mitochondrial function was significantly downregulated. These results show that the toxicity of the nanoparticles affects protein expression even if there is no change in cell morphology at the beginning of exposure to SiO2 NPs. The levels of reactive oxygen species changed significantly after 10 h of exposure to SiO2 NPs, and the expression of proteins associated with oxidative phosphorylation, as well as the immune system, was upregulated. Eventually, these changes in protein expression induced HepG2 cell death. This study provides insights into cytotoxicity evaluation at early stages of exposure to SiO2 NPs through in vitro experiments.
Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development
No full textSmoking is a major cause of lung cancer, and 4？(methylnitrosamino)？1？(3？pyridyl)？1？butanone (NNK) is one of the most important carcinogens in cigarette smoke. NNK modulates the expression of peroxiredoxin (Prdx) I in lung cancer. Prdx1 is upregulated in lung squamous cell carcinoma and lung adenocarcinoma, and considered a potential biomarker for lung cancer. The current article reviewed the role and regulatory mechanisms of Prdx1 in NNK？induced lung cancer cells. Prdx1 protects erythrocytes and DNA from NNK？induced oxidative damage, prevents malignant transformation of cells and promotes cytotoxicity of natural killer cells, hence suppressing tumor formation. In addition, Prdx1 has the ability to prevent NNK？induced lung tumor metabolic activity and generation of large amount of reactive oxygen species (ROS) and ROS？induced apoptosis, thus promoting tumor cell survival. In contrast to this, Prdx1, together with NNK, can promote the epithelial？mesenchymal transition and migration of lung tumor cells. The signaling pathways associated with NNK and Prdx1 in lung cancer cells have been discussed in present review; however, numerous potential pathways are yet to be studied. To develop novel methods for treating NNK？induced lung cancer, and improve the survival rate of patients with lung cancer, further research is needed to understand the complete mechanism associated with NNK.
Stretchable and suturable fibre sensors for wireless monitoring of connective tissue strain
No full textImplantable sensors can be used to monitor biomechanical strain continuously. However, three key challenges need to be addressed before they can be of use in clinical practice: the structural mismatch between the sensors and tissue or organs should be eliminated; a practical suturing attachment process should be developed; and the sensors should be equipped with wireless readout. Here, we report a wireless and suturable fibre strain-sensing system created by combining a capacitive fibre strain sensor with an inductive coil for wireless readout. The sensor is composed of two stretchable conductive fibres organized in a double helical structure with an empty core, and has a sensitivity of around 12. Mathematical analysis and simulation of the sensor can effectively predict its capacitive response and can be used to modulate performance according to the intended application. To illustrate the capabilities of the system, we use it to perform strain measurements on the Achilles tendon and knee ligament in an ex vivo and in vivo porcine leg.
Single-molecule analysis of interaction between p53TAD and MDM2 using aerolysin nanopores
No full textProtein？protein interactions (PPIs) are regarded as important, but undruggable targets. Intrinsically disordered p53 transactivation domain (p53TAD) mediates PPI with mouse double minute 2 (MDM2), which is an attractive anticancer target for therapeutic intervention. Here, using aerolysin nanopores, we probed the p53TAD peptide/MDM2 interaction and its modulation by small-molecule PPI inhibitors or p53TAD phosphorylation. Although the p53TAD peptide showed short-lived (<100 ms) translocation, the protein complex induced the characteristic extraordinarily long-lived (0.1 s ∼ tens of min) current blockage, indicating that the MDM2 recruitment by p53TAD peptide almost fully occludes the pore. Simultaneously, the protein complex formation substantially reduced the event frequency of short-lived peptide translocation. Notably, the addition of small-molecule PPI inhibitors, Nutlin-3 and AMG232, or Thr18 phosphorylation of p53TAD peptide, were able to diminish the extraordinarily long-lived events and restore the short-lived translocation of the peptide rescued from the complex. Taken together, our results elucidate a novel mechanism of single-molecule sensing for analyzing PPIs and their inhibitors using aerolysin nanopores. This novel methodology may contribute to remarkable improvements in drug discovery targeted against undruggable PPIs.
Development of 6E3 antibody-mediated SERS immunoassay for drug-resistant influenza virus
No full textInfluenza viruses are responsible for several pandemics and seasonal epidemics and pose a major public health threat. Even after a major outbreak, the emergence of drug-resistant influenza viruses can pose disease control problems. Here we report a novel 6E3 monoclonal antibody capable of recognizing and binding to the H275Y neuraminidase (NA) mutation, which has been associated with reduced susceptibility of influenza viruses to NA inhibitors. The 6E3 antibody had a KD of 72.74 μM for wild-type NA and 32.76 pM for H275Y NA, suggesting that it can identify drug-resistant pandemic H1N1 (pH1N1) influenza virus. Molecular modeling studies also suggest the high-affinity binding of this antibody to pH1N1 H275Y NA. This antibody was also subject to dot-blot, enzyme-linked immunosorbent assay, bare-eye detection, and lateral flow assay to demonstrate its specificity to drug-resistant pH1N1. Furthermore, it was immobilized on Au nanoplate and nanoparticles, enabling surface-enhanced Raman scattering (SERS)-based detection of the H275Y mutant pH1N1. Using 6E3 antibody-mediated SERS immunoassay, the drug-resistant influenza virus can be detected at a low concentration of 102 plaque-forming units/mL. We also detected pH1N1 in human nasopharyngeal aspirate samples, suggesting that the 6E3-mediated SERS assay has the potential for diagnostic application. We anticipate that this newly developed antibody and SERS-based immunoassay will contribute to the diagnosis of drug-resistant influenza viruses and improve treatment strategies for influenza patients.