• Title/Summary/Keyword: Systems Biology

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Characterization of ovarian culture in vitro and sex steroids in vivo by recombinant eel gonadotropin treatments in the eel Anguilla japonica

  • Kim, Dae-Geun;Kim, Jung-Hyun;Baek, Hea-Ja;Kim, Shin-Kwon;Min, Kwan-Sik;Kim, Dae-Jung
    • Fisheries and Aquatic Sciences
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    • v.25 no.1
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    • pp.12-19
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    • 2022
  • In the present study, we investigated the effects of recombinant eel gonadotropins (rec-GTHs) on maturation induction in immature ovarian culture in vitro and sex steroid hormones in vivo in the Japanese eel Anguilla japonica. To study the in vitro effects of rec-GTHs on estradiol-17β (E2) production in immature ovarian tissues, ovarian tissues were incubated with different doses of rec-follicle-stimulating hormone (rec-FSH) or rec-luteinizing hormone (rec-LH). The results revealed that the E2 levels in the rec-FSH (0.1, 0.5, or 1 ㎍/mL)- and rec-LH (0.1 or 0.5 ㎍/mL)-treated groups were significantly higher than those in the female eels from the control group. Furthermore, to investigate the in vivo effects of rec-GTHs on the gonadosomatic index (GSI) and plasma sex steroid hormone levels, the eels were injected intraperitoneally with eel's ringer (control), salmon pituitary extract (SPE; for female eels), human chorionic gonadotropin (hCG; for male eels), rec-FSH, rec-LH, and rec-FSH + rec-LH once a week. The results revealed that except for the SPE and the hCG groups, none of the groups exhibited a significant difference in GSI values. However, in vivo plasma E2 levels increased at the end of 4 weeks after rec-FSH treatment in female eels. Based on these results, it is suggested that rec-GTHs may have a positive effect on sexual maturation in female eels; however, further studies on complementary rec-protein production systems and additional glycosylation of rec-hormones are needed to elucidate hormone bioactivity in vivo and in vitro.

A report of 24 unrecorded bacterial species in Korea belonging to the Phyla Proteobacteria and Bacteroidetes isolated in 2020

  • Kim, Ju-Young;Yoon, Jung-Hoon;Joh, Kiseong;Seong, Chi-Nam;Kim, Won-Yong;Im, Wan-Taek;Cha, Chang-Jun;Kim, Seung-Bum;Jeon, Che-Ok;Seo, Taegun;Kim, Myung Kyum
    • Journal of Species Research
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    • v.11 no.3
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    • pp.133-142
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    • 2022
  • In 2020, 24 bacterial strains were isolated from algae, kudzu leaf, mud, pine cone, seashore sand, sea water, soil, tidal flat, and wetland from the Republic of Korea. Isolated bacterial strains were identified based on 16S rRNA gene sequences, and those exhibiting at least 98.7% sequence similarity with known bacterial species, but not reported in Korea, were highlighted as unrecorded species. These isolates were allocated to the phyla Bacteroidetes and Proteobacteria as unrecorded species in Korea. The four Bacteroidetes strains were classified into the families Chitinophagaceae, Flavobacteriaceae, and Sphingobacteriaceae (of the orders Chitinophagales, Flavobacteriales, and Sphingobacteriales, respectively). The 20 Proteobacteria strains belonged to the Aeromonadaceae, Marinobacter, Microbulbiferaceae, Enterobacteriaceae, Erwiniaceae, Morganellaceae, Yersiniaceae, Lysobacteraceae, Halomonadaceae, Moraxellaceae, Pseudomonadaceae, Steroidobacteraceae, Xanthomonadaceae, and Myxococcaceae (of the orders Aeromonadales, Alteromonadales, Cellvibrionales, Enterobacterales, Lysobacterales, Oceanospirillales, Pseudomonadales, Steroidobacter, Xanthomonadales, and Myxococcales). This study focused on the description of 24 unreported bacterial species in Korea in the phyla Bacteroidetes and Proteobacteria belonging to six classes.

Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis

  • Ruo Yu Meng;Cong Shan Li;Dan Hu;Soon-Gu Kwon;Hua Jin;Ok Hee Chai;Ju-Seog Lee;Soo Mi Kim
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.493-511
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    • 2023
  • Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

Systemic and molecular analysis dissect the red ginseng induction of apoptosis and autophagy in HCC as mediated with AMPK

  • Young Woo Kim;Seon Been Bak;Won-Yung Lee;Su Jin Bae;Eun Hye Lee;Ju-Hye Yang;Kwang Youn Kim;Chang Hyun Song;Sang Chan Kim;Un-Jung Yun;Kwang Il Park
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.479-491
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    • 2023
  • Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

Insight from sirtuins interactome: topological prominence and multifaceted roles of SIRT1 in modulating immunity, aging, and cancer

  • Nur Diyana Zulkifli;Nurulisa Zulkifle
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.23.1-23.9
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    • 2023
  • The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.

The contribution of the nervous system in the cancer progression

  • Hongryeol Park;Chan Hee Lee
    • BMB Reports
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    • v.57 no.4
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    • pp.167-175
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    • 2024
  • Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.

Ecological health assessment of Mae Kha Canal, Chiang Mai Province, Thailand in 2023

  • Onalenna Manene;Nick Deadman;Chotiwut Techakijvej;Songyot Kullasoot;Pitak Sapewisut;Nattawut Sareein;Chitchol Phalaraksh
    • Journal of Ecology and Environment
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    • v.48 no.1
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    • pp.110-119
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    • 2024
  • Background: The Mae Kha Canal is one of Chiang Mai's most important waterways. It supports local agriculture, irrigation, and transportation as well as provides stormwater drainage to prevent floods. Due to the unregulated rapid urbanization of the city and lack of efficient waste and wastewater management systems over the past few decades, the canal has become heavily polluted. This study aimed to evaluate the water quality of Mae Kha canal through assessment of the physico-chemical water quality and coliform bacteria. Moreover, benthic macroinvertebrates were samples and assessed using the Biological Monitoring Working Party (BMWPThai) and Average Score Per Taxon (ASPTThai) as biological indices. Results: The physico-chemical showed low dissolved oxygen levels, high levels of ammonia and phosphates, and elevated levels of biochemical oxygen demand, indicating that the water quality had significantly deteriorated. The canal was found to be heavily polluted, with most sites falling into the polluted to very heavily polluted. Coliform bacteria analysis revealed alarmingly high levels of total coliform bacteria and fecal coliform bacteria in the canal. The BMWPThai and ASPTThai scores indicated poor to very poor water quality. Conclusions: The physico-chemical and coliform bacteria indicated that the water quality of the Mae Kha canal had significantly deteriorated. The biological indices also indicated the poor to very poor water quality. This study underscores the urgent need for comprehensive remediation efforts, emphasizing strategic planning, investment, and community engagement to revive the canal's ecological health and water quality.

Effects of In Vitro Culture Systems on the Development of In Vitro Fertilized or DNA-Microinjected Embryos (체외 배양 체계가 체외수정 및 유전자 미세주입 수정란의 발달에 미치는 영향)

  • Park Y. S.;Min K. S.
    • Reproductive and Developmental Biology
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    • v.29 no.3
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    • pp.181-186
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    • 2005
  • This experiment was conducted to investigate effects of the two different in vitro production systems, serumcontaining system (IVM, IVF and IVC; TCM199, TALP and CR1aa) and serum-free system (IVM, IVF and IVC; IVMD101, IVMD100 and IVMD101), on the development of in vitro fertilized or DNA-microiniected embryos. We also examined the effect of DNA dosage and its expression pattern in embryos. The DNA used for microinjection was a green fluorescence protein gene. The development rates to $\geq$ 2cell, 8cell and blastocyst stage were significantly higher in vitro fertilized embryos than those in DNA-microinjected embryos. The development rate to the 8-cell stage was significantly higher in serum-free system than in serum-containing system (p<0.05; $3.3\%\;vs.\;15.5\%\;and\;21.4\%$, respectively). The development rates to the blastocyst stage of in vitro fertilzed or DNA-microinjected embryos between two different culture system ($2.7\%\;vs.\;2.3\%\;and\;23.0\%\;vs.\;23.6\%$, respectively) were not different. The development rates of embryos injected 2 ng/uL DNA was higher. than those of embryos injected 4 or 8 ng/uL DNA. The GFP expression rate of 1-cell embryos was significantly higher than that of 2-cell and 4-cell embryos, whereas the rates were not different between 4-cell and blastocyst-stage embryos.

Generation, Diversity Determination, and Application to Antibody Selection of a Human Naïve Fab Library

  • Kim, Sangkyu;Park, Insoo;Park, Seung Gu;Cho, Seulki;Kim, Jin Hong;S.Ipper, Nagesh;Choi, Sun Shim;Lee, Eung Suk;Hong, Hyo Jeong
    • Molecules and Cells
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    • v.40 no.9
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    • pp.655-666
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    • 2017
  • We constructed a large $na{\ddot{i}}ve$ human Fab library ($3{\times}10^{10}$ colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and ${\kappa}$ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 pyrosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries. The frequency of somatic hypermutations (SHMs) in heavy-chain complementarity determining region (HCDR)1 and HCDR2 are higher compared with the natural IgM repertoire. Analysis of position-specific SHMs in CDRs indicates that asparagine, threonine, arginine, aspartate and phenylalanine are the most frequent non-germline residues on the antibody-antigen interface and are converted mostly from the germline residues, which are highly represented in germline SHM hotspots. The amino acid composition and length-dependent changes in amino acid frequencies of HCDR3 are similar to those in previous reports, except that frequencies of aspartate and phenylalanine are a little higher in our repertoire. Taken together, the results show that this antibody library shares common features of natural antibody repertoires and also has unique features. The antibody library will be useful in the generation of human antibodies against diverse antigens, and the information about the diversity of natural antibody repertoires will be valuable in the future design of synthetic human antibody libraries with high functional diversity.

Evaluation of carbon flux in vegetative bay based on ecosystem production and CO2 exchange driven by coastal autotrophs

  • Kim, Ju-Hyoung;Kang, Eun Ju;Kim, Keunyong;Jeong, Hae Jin;Lee, Kitack;Edwards, Matthew S.;Park, Myung Gil;Lee, Byeong-Gweon;Kim, Kwang Young
    • ALGAE
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    • v.30 no.2
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    • pp.121-137
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    • 2015
  • Studies on carbon flux in the oceans have been highlighted in recent years due to increasing awareness about climate change, but the coastal ecosystem remains one of the unexplored fields in this regard. In this study, the dynamics of carbon flux in a vegetative coastal ecosystem were examined by an evaluation of net and gross ecosystem production (NEP and GEP) and $CO_2$ exchange rates (net ecosystem exchange, NEE). To estimate NEP and GEP, community production and respiration were measured along different habitat types (eelgrass and macroalgal beds, shallow and deep sedimentary, and deep rocky shore) at Gwangyang Bay, Korea from 20 June to 20 July 2007. Vegetative areas showed significantly higher ecosystem production than the other habitat types. Specifically, eelgrass beds had the highest daily GEP ($6.97{\pm}0.02g\;C\;m^{-2}\;d^{-1}$), with a large amount of biomass and high productivity of eelgrass, whereas the outer macroalgal vegetation had the lowest GEP ($0.97{\pm}0.04g\;C\;m^{-2}\;d^{-1}$). In addition, macroalgal vegetation showed the highest daily NEP ($3.31{\pm}0.45g\;C\;m^{-2}\;d^{-1}$) due to its highest P : R ratio (2.33). Furthermore, the eelgrass beds acted as a $CO_2$ sink through the air-seawater interface according to NEE data, with a carbon sink rate of $0.63mg\;C\;m^{-2}\;d^{-1}$. Overall, ecosystem production was found to be extremely high in the vegetated systems (eelgrass and macroalgal beds), which occupy a relatively small area compared to the unvegetated systems according to our conceptual diagram of a carbon-flux box model. These results indicate that the vegetative ecosystems showed significantly high capturing efficiency of inorganic carbon through coastal primary production.