Korea Research Institute of Bioscience and Biotechnology
KRIBB Open Access RepositoryNot a member yet
15834 research outputs found
Sort by
Metabolic spectrum of liver failure in type 2 diabetes and obesity: from NAFLD to NASH to HCC
No full textLiver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type 2 diabetes contributes to biological processes driving the severity of NAFLD, the primary cause for development of chronic liver diseases. In the last 20 years, the rate of non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs for treatment of NAFLD and NASH, a class of thiazolidinediones (TZDs) drugs for the treatment of type 2 diabetes is sometimes used to improve liver failure despite the risk of side effects. Therefore, diagnosis, prevention, and treatment of the development and progression of NAFLD and NASH are important issues. In this review, we will discuss the pathogenesis of NAFLD/NASH and NAFLD/NASH-derived HCC and the current promising pharmacological therapies of NAFLD/NASH. Further, we will provide insights into “adipose-derived adipokines” and “liver-derived hepatokines” as diagnostic and therapeutic targets from NAFLD to HCC.
Safety pharmacology of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle platform
No full textThe present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300？mg/kg and 100？mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200？μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5？h (30？min) post-dose at both sexes in mice, with a single 300？mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1？h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200？μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.
Anti-obesity effect of pine needle extract on high-fat diet-induced obese mice
No full textBackground: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism. Methods: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons. Mice were fed a normal or high-fat diet for 12 weeks, then received PNE for the last 2 weeks to measure the following physiological indices: Body weight, food intake, fat/lean mass, glucose metabolism, and plasma leptin levels. In addition, changes of thermogenic, lipolytic, and lipogenetic markers were evaluated in brown adipose tissue (BAT) and white adipose tissue (WAT) by western blotting, respectively. Results: PNE increased hypothalamic POMC neuronal activity, and the effect was abolished by blockade of melanocortin 3/4 receptors (MC3/4Rs). PNE decreased body weight, fat mass, plasma leptin levels, and improved glucose metabolism after high-fat-induced obesity. However, PNE did not change the expression of thermogenic markers of the BAT in HFD fed groups, but decreased only the lipogenetic markers of WAT. This study suggests that PNE has a potent anti-obesity effect, inhibiting lipogenesis in WAT, even though HFD-induced leptin resistance-mediated disruption of POMC neuronal activity.
Mitochondrial transplantation as a novel therapeutic strategy for mitochondrial diseases
No full textMitochondria are the major source of intercellular bioenergy in the form of ATP. They are necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation of metabolism and apoptosis. Mitochondrial dysfunction has been observed in variety of diseases such as cardiovascular disease, aging, type 2 diabetes, cancer and degenerative brain disease. In other words, the interpretation and regulation of mitochondrial signals has the potential to be applied as a treatment for various diseases caused by mitochondrial disorders. In recent years, mitochondrial transplantation has increasingly been a topic of interest as an innovative strategy for the treatment of mitochondrial diseases by augmentation and replacement of mitochondria. In this review, we focus on diseases that are associated with mitochondrial dysfunction and highlight studies related to the rescue of tissue-specific mitochondrial disorders. We firmly believe that mitochondrial transplantation is an optimistic therapeutic approach in finding a potentially valuable treatment for a variety of mitochondrial diseases.
Development of monitoring and detection kit for DDT in agricultural environments
No full textDDT 및 유기인계 잔류농약성분의 신속 감지용 센서 및 가시화기술 개발ABM460201
Structure-based modification of pyrazolone derivatives to inhibit mTORC1 by targeting the leucyl-tRNA synthetase-RagD interaction
No full textThe enzyme leucyl-tRNA synthetase (LRS) and the amino acid leucine regulate the mechanistic target of rapamycin (mTOR) signaling pathway. Leucine-dependent mTORC1 activation depends on GTPase activating protein events mediated by LRS. In a prior study, compound BC-LI-0186 was discovered and shown to interfere with the mTORC1 signaling pathway by inhibiting the LRS-RagD interaction. However, BC-LI-0186 exhibited poor solubility and was metabolized by human liver microsomes. In this study, in silico physicochemical properties and metabolite analysis of BC-LI-0186 are used to investigate the addition of functional groups to improve solubility and microsomal stability. In vitro experiments demonstrated that 7b and 8a had improved chemical properties while still maintaining inhibitory activity against mTORC1. The results suggest a new strategy for the discovery of novel drug candidates and the treatment of diverse mTORC1-related diseases.
The defense response involved in sweetpotato resistance to root-knot nematode Meloidogyne incognita: comparison of root transcriptomes of resistant and susceptible sweetpotato cultivars with respect to induced and constitutive defense responses
No full textSweetpotato (Ipomoea batatas [L.] Lam) is an economically important, nutrient- and pigment-rich root vegetable used as both food and feed. Root-knot nematode (RKN), Meloidogyne incognita, causes major yield losses in sweetpotato and other crops worldwide. The identification of genes and mechanisms responsible for resistance to RKN will facilitate the development of RKN resistant cultivars not only in sweetpotato but also in other crops. In this study, we performed RNA-seq analysis of RKN resistant cultivars (RCs; Danjami, Pungwonmi and Juhwangmi) and susceptible cultivars (SCs; Dahomi, Shinhwangmi and Yulmi) of sweetpotato infected with M. incognita to examine the induced and constitutive defense response-related transcriptional changes. During induced defense, genes related to defense and secondary metabolites were induced in SCs, whereas those related to receptor protein kinase signaling and protein phosphorylation were induced in RCs. In the uninfected control, genes involved in proteolysis and biotic stimuli showed differential expression levels between RCs and SCs during constitutive defense. Additionally, genes related to redox regulation, lipid and cell wall metabolism, protease inhibitor and proteases were putatively identified as RKN defense-related genes. The root transcriptome of SCs was also analyzed under uninfected conditions, and several potential candidate genes were identified. Overall, our data provide key insights into the transcriptional changes in sweetpotato genes that occur during induced and constitutive defense responses against RKN infection.
Luteolin orchestrates porcine oocyte meiotic progression by maintaining organelle dynamics under oxidative stress
No full textIncreasing evidence has demonstrated that oxidative stress impairs oocyte maturation, but the underlying mechanisms remain largely unknown. Here, for the first time, we examined the antioxidant role of luteolin in meiotic progression and the underlying mechanisms. Supplementation of 5 μM luteolin increased the rates of first polar body extrusion and blastocyst formation after parthenogenetic activation, and the expression levels of oocyte competence (BMP15 and GDF9)-, mitogen-activated protein kinase (MOS)-, and maturation promoting factor (CDK1 and Cyclin B)-related genes were also improved. Luteolin supplementation decreased intracellular reactive oxygen species levels and increased the expression levels of oxidative stress-related genes (SOD1, SOD2, and CAT). Interestingly, luteolin alleviated defects in cell organelles, including actin filaments, the spindle, mitochondria, the endoplasmic reticulum, and cortical granules, caused by H2O2 exposure. Moreover, luteolin significantly improved the developmental competence of in vitro-fertilized embryos in terms of the cleavage rate, blastocyst formation rate, cell number, cellular survival rate, and gene expression and markedly restored the competencies decreased by H2O2 treatment. These findings revealed that luteolin supplementation during in vitro maturation improves porcine meiotic progression and subsequent embryonic development by protecting various organelle dynamics against oxidative stress, potentially increasing our understanding of the underlying mechanisms governing the relationship between oxidative stress and the meiotic events required for successful oocyte maturation.
Sound waves promote Arabidopsis thaliana root growth by regulating root phytohormone content
No full textSound waves affect plants at the biochemical, physical, and genetic levels. However, the mechanisms by which plants respond to sound waves are largely unknown. Therefore, the aim of this study was to examine the effect of sound waves on Arabidopsis thaliana growth. The results of the study showed that Arabidopsis seeds exposed to sound waves (100 and 100 + 9k Hz) for 15 h per day for 3 day had significantly longer root growth than that in the control group. The root length and cell number in the root apical meristem were significantly affected by sound waves. Furthermore, genes involved in cell division were upregulated in seedlings exposed to sound waves. Root development was affected by the concentration and activity of some phytohormones, including cytokinin and auxin. Analysis of the expression levels of genes regulating cytokinin and auxin biosynthesis and signaling showed that cytokinin and ethylene signaling genes were downregulated, while auxin signaling and biosynthesis genes were upregulated in Arabidopsis exposed to sound waves. Additionally, the cytokinin and auxin concentrations of the roots of Arabidopsis plants increased and decreased, respectively, after exposure to sound waves. Our findings suggest that sound waves are potential agricultural tools for improving crop growth performance.