• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.575-583
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• 2021

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.695-705
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• 2021

Background: Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods: We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results: We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion: Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.405-416
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• 2021

Background: This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague-Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 ㎍/day; and Group SOG192, SOG at 192 ㎍/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.650-657
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• 2021

Metformin is an anti-diabetic drug and has anticancer effects on various cancers. Several studies have suggested that metformin reduces cell proliferation and stimulates cell-cycle arrest and apoptosis. However, the definitive molecular mechanism of metformin in the pathophysiological signaling in endometrial tumorigenesis and metastasis is not clearly understood. In this study, we examined the effects of metformin on the cell viability and apoptosis of human cervical HeLa and endometrial HEC-1-A and KLE cancer cells. Metformin suppressed cell growth in a dose-dependent manner and dramatically evoked apoptosis in HeLa cervical cancer cells, while apoptotic cell death and growth inhibition were not observed in endometrial (HEC-1-A, KLE) cell lines. Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphate-activated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. To determine why the anti-proliferative effects are observed only in HeLa cells, we examined the expression level of liver kinase B1 (LKB1) since metformin and LKB1 share the same signalling system, and we found that the LKB1 gene is not expressed only in HeLa cancer cells. Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.

• Plant Breeding and Biotechnology
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• v.5 no.2
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• pp.123-133
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• 2017

AP2/EREBP gene family consists of transcription factor genes with a conserved AP2 DNA-binding domain and is involved in various biological processes. AP2/EREBP gene families were identified through genome-wide searches in five Cucurbitaceae species including cucumber, wild cucumber, melon, watermelon, and bitter gourd, which consisted of more than 100 genes in each of the five species. The gene families were further divided into five groups including four subfamilies (ERF, DREB, AP2 and RAV) and a soloist group. Among the subfamilies, DREB subfamily which is known to be related to abiotic stress response was more analyzed and a total of 25 genes were identified as Cucurbitaceae homologues of Arabidopsis CBF/DREB1 genes which are important for abiotic stress-response and tolerance. In silico expression profiling using RNA-Seq data revealed diverse expression patterns of cucumber AP2/EREBP genes. AP2/EREBP gene families identified in this study will be valuable for understanding the stress response mechanism as well as facilitating molecular breeding in Cucurbitaceae crops.

• Environmental Engineering Research
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• v.24 no.1
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• pp.1-16
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• 2019

N-nitrosodimethylamine (NDMA) is a typical nitrogen disinfection by-product, which has posed a potential threat to human health during drinking water disinfection. Because of the well-known effects of mutagenesis, carcinogenesis and teratogenesis, the high detection rate in water engineering systems (such as coagulation, membrane filtration and biological systems), and difficulty to remove, it has received wide concern in the field of water engineering systems. The NDMA is a low molecular weight hydrophilic organic substance, which is difficult to remove. Also, the mechanism for NDMA formation is also recognized to be complex, and many steps still needed to be further evaluated. Therefore, the mechanistic knowledge on NDMA formation potential and their removal processes is of particularly interest. Few papers summarize the occurrence and control of NDMA in water engineering systems. It is for this reason that the content of this paper is particularly important for us to understand and control the amount of NDMA thus reducing the threat of disinfection by-products to drinking water. Four parts including the mechanisms for the NDMA formation potential, the factors affecting the NDMA formation potential, the technologies for removal of NDMA are summarized. Finally, some definite suggestions are given.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.107-116
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• 2019

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.10
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• pp.1483-1490
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• 2019

Objective: To explore the molecular mechanisms of fat metabolism and deposition in pigs, an experiment was conducted to identify hepatic mRNAs and miRNAs expression and determine the potential interaction of them in two phenotypically extreme pig breeds. Methods: mRNA and miRNA profiling of liver from 70-day Jinhua (JH) and Landrace (LD) pigs were performed using RNA sequencing. Blood samples were taken to detect results of serum biochemistry. Bioinformatics analysis were applied to construct differentially expressed miRNA-mRNA network. Results: Serum total triiodothyronine and total thyroxine were significantly lower in Jinhua pigs, but the content of serum total cholesterol (TCH) and low-density lipoprotein cholesterol were strikingly higher. A total of 467 differentially expressed genes (DEGs) and 35 differentially expressed miRNAs (DE miRNAs) were identified between JH and LD groups. Gene ontology analysis suggested that DEGs were involved in oxidation-reduction, lipid biosynthetic and lipid metabolism process. Interaction network of DEGs and DE miRNAs were constructed, according to target prediction results. Conclusion: We generated transcriptome and miRNAome profiles of liver from JH and LD pig breeds which represent distinguishing phenotypes of growth and metabolism. The potential miRNA-mRNA interaction networks may provide a comprehensive understanding in the mechanism of lipid metabolism. These results serve as a basis for further investigation on biological functions of miRNAs in the porcine liver.

• Korean Chemical Engineering Research
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• v.57 no.3
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• pp.438-443
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• 2019

A new measurement method is suggested to quantify the phosphate poisoning of cathodic Pt catalyst for HT-PEMFC. To do that, hydrogen peroxide was used as an indicator to reduce the error which has been occurred in conventional electrochemical measurement such as CV or ORR RDE with high concentration of phosphate ions. As a result, the current density induced from the reaction of hydrogen peroxide decomposition increased proportionally to the concentration of phosphate ion while the conventional methods show has a significant error with high concentration of phosphate ion. Thus, it is confirmed that the suggested way is superior to the conventional measurement method for the quantification of phosphate ion poisoning in an atmosphere similar to the actual operation condition of HT-PEMFC.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.8
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• pp.1084-1094
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• 2019

Objective: The aim of this study was to select the candidate genes affecting meat quality and preliminarily explore the related molecular mechanisms in the Mashen pig. Methods: The present study explored genetic factors affecting meat quality in the Mashen pig using RNA sequencing (RNA-Seq). We sequenced the transcriptomes of 180-day-old Mashen and Large White pigs using longissimus dorsi to select differentially expressed genes (DEGs). Results: The results indicated that a total of 425 genes were differentially expressed between Mashen and Large White pigs. A gene ontology enrichment analysis revealed that DEGs were mainly enriched for biological processes associated with metabolism and muscle development, while a Kyoto encyclopedia of genes and genomes analysis showed that DEGs mainly participated in signaling pathways associated with amino acid metabolism, fatty acid metabolism, and skeletal muscle differentiation. A MCODE analysis of the protein-protein interaction network indicated that the four identified subsets of genes were mainly associated with translational initiation, skeletal muscle differentiation, amino acid metabolism, and oxidative phosphorylation pathways. Conclusion: Based on the analysis results, we selected glutamic-oxaloacetic transaminase 1, malate dehydrogenase 1, pyruvate dehydrogenase 1, pyruvate dehydrogenase kinase 4, and activator protein-1 as candidate genes affecting meat quality in pigs. A discussion of the related molecular mechanisms is provided to offer a theoretical basis for future studies on the improvement of meat quality in pigs.