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Acremonidin E produced by Penicillium sp. SNF123, a fungal endophyte of Panax ginseng, has antimelanogenic activities

  • Kim, Kyuri;Jeong, Hae-In;Yang, Inho;Nam, Sang-Jip;Lim, Kyung-Min
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.98-107
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    • 2021
  • Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

Anti-Endotoxin 9-Meric Peptide with Therapeutic Potential for the Treatment of Endotoxemia

  • Krishnan, Manigandan;Choi, Joonhyeok;Choi, Sungjae;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.31 no.1
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    • pp.25-32
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    • 2021
  • Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

Electron Transfer to Hydroxylase through Component Interactions in Soluble Methane Monooxygenase

  • Lee, Chaemin;Hwang, Yunha;Kang, Hyun Goo;Lee, Seung Jae
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.287-293
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    • 2022
  • The hydroxylation of methane (CH4) is crucial to the field of environmental microbiology, owing to the heat capacity of methane, which is much higher than that of carbon dioxide (CO2). Soluble methane monooxygenase (sMMO), a member of the bacterial multicomponent monooxygenase (BMM) superfamily, is essential for the hydroxylation of specific substrates, including hydroxylase (MMOH), regulatory component (MMOB), and reductase (MMOR). The diiron active site positioned in the MMOH α-subunit is reduced through the interaction of MMOR in the catalytic cycle. The electron transfer pathway, however, is not yet fully understood due to the absence of complex structures with reductases. A type II methanotroph, Methylosinus sporium 5, successfully expressed sMMO and hydroxylase, which were purified for the study of the mechanisms. Studies on the MMOH-MMOB interaction have demonstrated that Tyr76 and Trp78 induce hydrophobic interactions through π-π stacking. Structural analysis and sequencing of the ferredoxin domain in MMOR (MMOR-Fd) suggested that Tyr93 and Tyr95 could be key residues for electron transfer. Mutational studies of these residues have shown that the concentrations of flavin adenine dinucleotide (FAD) and iron ions are changed. The measurements of dissociation constants (Kds) between hydroxylase and mutated reductases confirmed that the binding affinities were not significantly changed, although the specific enzyme activities were significantly reduced by MMOR-Y93A. This result shows that Tyr93 could be a crucial residue for the electron transfer route at the interface between hydroxylase and reductase.

Cerebrotendinous xanthomatosis in a 10-year-old male presenting with Achilles tendon xanthoma and mild intellectual disability: A case report

  • Yoon, Ji Hye;Kim, Ka Young;Lee, Sang-Yun;Kim, Soo Yeon;Lee, Young Ah;Ki, Chang-Seok;Song, Junghan;Shin, Choong Ho;Lee, Yun Jeong
    • Journal of Genetic Medicine
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    • v.19 no.1
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    • pp.22-26
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    • 2022
  • Cerebrotendinous xanthomatosis (CTX) is a rare genetic disease caused by a deficiency of enzymes for the synthesis of bile acid, resulting in the accumulation of cholestanol with reduced chenodeoxycholic acid (CDCA) production and causing various symptoms such as chronic diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas in adolescence and young adulthood, and progressive neurologic dysfunction in adulthood. Because oral CDCA replacement therapy can effectively prevent disease progression, early diagnosis and treatment are critical in CTX. This study reports the case of CTX in a 10-year-old male who presented with Achilles tendon xanthoma and mild intellectual disability. Biochemical testing showed normal cholesterol and sitosterol levels but elevated cholestanol levels. Genetic testing showed compound heterozygous variants of CYP27A1, c.379C>T (p.Arg127Trp), and c.1214G>A (p.Arg405Gln), which confirmed the diagnosis of CTX. The patient had neither cataracts nor other focal neurologic deficits and showed no abnormalities on brain imaging. The patient received oral CDCA replacement therapy without any adverse effects; thereafter, the cholestanol level decreased and no disease progression was noted. The diagnostic possibility of CTX should be considered in patients with tendon xanthoma and normolipidemic conditions to prevent neurological deterioration.

Effect of reducing dietary crude protein level on growth performance, blood profiles, nutrient digestibility, carcass traits, and odor emissions in growing-finishing pigs

  • Aaron Niyonsaba;Xing Hao Jin;Yoo Yong Kim
    • Animal Bioscience
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    • v.36 no.10
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    • pp.1584-1595
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    • 2023
  • Objective: This study was conducted to evaluate the effect of a low-protein diet on growth performance, carcass traits, nutrient digestibility, blood profiles, and odor emissions in growing-finishing pigs. Methods: A total of 126 crossbred pigs ([Yorkshire×Landrace]×Duroc) with an average body weight (BW) of 38.56±0.53 kg were used for a 14-week feeding trial. Experimental pigs were allotted to one of 6 treatments in 3 replicates of 7 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with different levels of crude protein (CP). Phase 1 (early growing): 14%, 15%, 16%, 17%, 18%, 19%; phase 2 (late growing): 13%, 14%, 15%, 16%, 17%, 18%; phase 3 (early finishing): 12%, 13%, 14%, 15%, 16%, 17%; phase 4 (late finishing): 11%, 12%, 13%, 14%, 15%, 16%. All experimental diets in each phase were contained the same concentration of lysine (Lys), methionine (Met), threonine (Thr), and tryptophan (Trp). Results: Over the entire experimental period, there was no significant difference in BW, average daily feed intake, and gain-to-feed ratio among all treatments (p>0.05), but a quadratic effect (p = 0.04) was observed in average daily gain (ADG) during the late finishing phase with higher ADG in Group D. Blood urea nitrogen concentration linearly increased with an increase in dietary CP levels (p<0.01). Regarding nutrient digestibility, excreted nitrogen in urine and feces and nitrogen retention linearly increased as the CP level increased (p<0.01). A linear effect was observed with increasing CP levels in amines, ammonia, and hydrogen sulfide in odor emissions (p<0.01). No significant effects were observed in the measurements of carcass traits and meat characteristics (p>0.05). Conclusion: In phase feeding, reducing the CP level to 14% in early-growing pigs, 13% in late-growing pigs, 12% in early-finishing pigs, and 11% in late-finishing pigs is recommended.

Gram-Schmidt process based adaptive time-reversal processing (그람슈미트 과정 기반의 적응형 시역전 처리)

  • Donghyeon Kim;Gihoon Byun;J. S. Kim;Kee-Cheol Shin
    • The Journal of the Acoustical Society of Korea
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    • v.43 no.2
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    • pp.184-199
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    • 2024
  • Residual crosstalk has been considered as a major drawback of conventional time-reversal processing in the case of simultaneous multiple focusing. In this paper, the Gram-Schmidt process is applied to time-reversal processing to mitigate crosstalk in ocean waveguides for multiple probe sources. Experimental data-based numerical simulations confirm that nulls can be placed at multiple locations, and it is shown that different signals can be simultaneously focused at different probe source locations, ensuring distortionless responses in terms of active time-reversal processing. This focusing property is also shown to be much less affected by a reduction in the number of receivers than the adaptive time-reversal mirror method. The proposed method is shown to be effective in eliminating crosstalk in passive multi-input multi-output communications using sea-going data.

The Clinical and Genetic Characteristics of Three Korean Patients with Glycogen Storage Disease Type V (McArdle Disease) (세 명의 대한민국 제 V형 당원축적근육병(McArdle 병) 환자들의 유전학적 및 임상적 특성 보고)

  • Lee, Sunghee;Kang, Eungu;Kim, Yoonmyung;Lee, Beom Hee;Kim, Gu Hwan;Yoo, Han Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.2
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    • pp.93-101
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    • 2016
  • Purpose: McArdle disease, glycogen storage disease type V (GSD V), is one of the most common adolescent-onset glycogen storage diseases. It is caused by recessive mutations in PYGM encoding myophosphorylase, which is critical to glycogen metabolism. Since only a few korean patients have been reported, we will observe the clinical and genetic features of three korean patients with McArdle disease. Methods: We retrospectively reviewed the medical records of three patients with genetically confirmed McArdle disease, including the results of forearm ischemic exercise test, electromyogram, nerve conduction velocity, muscle biopsy, and PYGM analysis in peripheral leukocytes. Results: All three cases were males and their age of symptom onset was 12, 5, 14 years old, respectively. A high basal level of serum creatine kinase was noted in all three patients. They experienced the recurrent episodes of rhabdomyolysis, but second wind phenomenon was not definite. In muscle biopsy, subsarcolemmal space vacuoles including periodic acid schiff stained materials were found in two patients, while no evidence of glycogen storage disease was found in the other. A total of five different mutations, $p.Arg50^*$, p.Trp798Arg, $p.Arg50^*$, p.Glu779del, $p.Asp511Thrfs^*28$ and p.Phe710del, were found in three patients. Avoidance of isometric exercise, aerobic exercise and glucose intake before each exercise were recommended for all patients. Conclusion: The three Korean patients with McArdle disease showed the typical manifestations of the condition. The most mutations were private. Therefore, identification of more cases with long-term follow-up will be required to understand the clinical and genetic features of this disease among Korean population.

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Inhibitory Effects of Myelophycus simplex Papenfuss Methanol Extract on Melanogenesis in B16F10 Melanoma Cells (바위수염 메탄올 추출물이 B16F10 흑색종 세포에서의 멜라닌합성에 미치는 영향)

  • Kim, Hyang Suk;Cheon, Ji Min;Kwon, Da Hye;Choi, Eun Ok;Kim, Min Ju;Choi, Yung Hyun;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.1
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    • pp.34-38
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    • 2017
  • Myelophycus simplex Papenfuss, a type of brown algae, is known to be majorly distributed in along the southern coast of Korea and Japan. The purpose of this study was to investigate the effects of M. simplex Papenfuss methanol extract (MSPME) on melanogenesis in ${\alpha}$-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells. Melanin contents of B16F10 melanoma cells were decreased by 27, 41, and 59% in a dose-dependent manner, upon MSPME treatment at 100, 300, and $500{\mu}g/mL$, respectively. Tyrosinase activities in B16F10 melanoma cells were decreased by 18, 49, and 61% in a dose-dependent manner, upon MSPME treatment at 100, 300, and $500{\mu}g/mL$, respectively. MSPME suppressed expression of tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and melanocyte-inducing transcription factor in B16F10 melanoma cells. Concentration of $50{\mu}g/mL$ of MSPME especially induced greater decreases in tyrosinase activity, melanin contents, and melanogenic enzyme protein expressions. This results indicate that MSPME inhibits melanin synthesis and tyrosinase activity, and M. simplex Papenfuss extract may be an ideal candidate as a skin whitening agent.

Genetic Variation and Population Specific Mitochondrial DNA Haplotype Found in the Jeju Native Pig Population (제주재래돼지 집단서 집단특이적 mtDNA Haplotype과 유전적 다양성)

  • Han, S.H.;Cho, I.C.;Lee, C.E.;Lee, S.S.;Kang, S.Y.;Choi, Y.L.;Oh, W.Y.;Sung, P.N.;Ko, S.B.;Oh, M.Y.;Ko, M.S.
    • Journal of Animal Science and Technology
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    • v.46 no.6
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    • pp.917-924
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    • 2004
  • Using PCR-RFLP haplotyping for the mitochondrial DNA(mtDNA) fragment containing the NADH dehydrogenase 2 gene(ND2) and three tRNA genes(tRNA-Met, tRNA-Trp and tRNA-Ala), we characterized the genetic diversity of five pig breeds including Jeju native pigs. mtDNA polymorphisms showing distinct cleavage patterns were found in the pig breeds. Two digestion patterns were detected when HaeIII- and Hinfl-RFLP, and four in the Tsp5091-RFLP analyses. Combining the three restriction enzyme digestion patterns found in five different pig breeds, four mtDNA haplotypes were observed and the haplotype frequencies were significantly different by the pig breeds. A monomorphic haplotype, mtWB, was observed in both Korean wild boars and Large White pigs. Both Duroc and Landrace pigs contained two haplotypes suggesting their multiple maternal lineages. Jeju native pig has two haplotypes(mtJN and mtJD). Of these, mtJN is identified as a Jeju native pig specific haplotype. This study suggested that more than two progenitor populations have been taken part in the domestication process of the Jeju native pig population, and/or probably subsequent crossing with other pig breeds from near east Asia. Unlike with our prediction, there was no direct evidence under molecular levels on the maternal introgression of Korean wild boar in the domestication of Jeju native pigs. In conclusion, specificity of mtDNA haplotypes related to pig breeds win be useful for identifying the maternal lineage as wen as constructing the genealogical pedigree in pigs.

Antimutagenic and Cytotoxic Effects of Acer ginnala Max. Bark Extracts (신나무 껍질 추출물의 항돌연변이원성 및 세포독성 효과)

  • Oh Heung-Seok;Cui Cheng-Bi;Choi Hyung-Taek;Kim Soo-Hyun;Jeon Mi-Sun;Ham Seung-Shi
    • Food Science and Preservation
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    • v.11 no.4
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    • pp.550-556
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    • 2004
  • In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.