Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the upstream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA reductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.
Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.
Journal of The Korean Society of Grassland and Forage Science
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v.42
no.3
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pp.195-200
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2022
Sulfur is an essential element in plants, including amino acids, vitamin synthesis, and acting as an antioxidant. However, the interaction between endogenous sulfur and proline synthesis has not been yet fully documented. White clover (Trifolium repens L.) is known as a species highly sensitive to sulfate supply. Therefore, this study aimed to elucidate the role of sulfur in regulating proline metabolism in relation to ammonia detoxification and hydrogen peroxide (H2O2) accumulation in white clover. The detached leaves of white clover were immersed in solution containing different concentration of sulfate (0, 10, 100, and 1000 mM MgSO4). As MgSO4 concentrations were increased, the concentration of H2O2 increased up to 2.5-fold compared to control, accompanied with H2O2 detection in leaves. Amino acid concentrations significantly increased only at higher levels (100 and 1000 mM MgSO4). No significant difference was observed in protein concentration. Proline and ∆1-pyrroline-5-carboxylate (P5C) concentrations slightly decreased at 10 and 100 mM MgSO4 treatments, whereas it rapidly increased over 1.9-fold at 1000 mM MgSO4 treatment. Ammonia concentrations gradually increased up to 8.6-fold. These results indicate that exogenous sulfur levels are closely related to H2O2 and ammonia synthesis but affect proline biosynthesis only at a higher level.
Homeostatic regulation of meristematic stem cells accomplished by maintaining a balance between stem cell self-renewal and differentiation is critical for proper plant growth and development. The quiescent center (QC) regulates root apical meristem homeostasis by maintaining stem cell fate during plant root development. Cell cycle checkpoints, such as anaphase promoting complex/cyclosome/cell cycle switch 52 A2 (APC/CCCS52A2), strictly control the low proliferation rate of QC cells. Although APC/CCCS52A2 plays a critical role in maintaining QC cell division, the molecular mechanism that regulates its activity remains largely unknown. Here, we identified SCFFBS1, a ubiquitin E3 ligase, as a key regulator of QC cell division through the direct proteolysis of CCS52A2. FBS1 activity is positively associated with QC cell division and CCS52A2 proteolysis. FBS1 overexpression or ccs52a2-1 knockout consistently resulted in abnormal root development, characterized by root growth inhibition and low mitotic activity in the meristematic zone. Loss-of-function mutation of FBS1, on the other hand, resulted in low QC cell division, extremely low WOX5 expression, and rapid root growth. The 26S proteasome-mediated degradation of CCS52A2 was facilitated by its direct interaction with FBS1. The FBS1 genetically interacted with APC/CCCS52A2-ERF115-PSKR1 signaling module for QC division. Thus, our findings establish SCFFBS1-mediated CCS52A2 proteolysis as the molecular mechanism for controlling QC cell division in plants.
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.36
no.1
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pp.50-63
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2023
Objectives : This study used a network pharmacology approach to explore the active compounds and therapeutic mechanisms of Yijin-tang on Meniere's disease. Methods : The active compounds of Yijin-tang were screened via the TCMSP database and their target proteins were screened via the STITCH database. The GeneCard was used to establish the Meniere's disease-related genes. The intersection targets were obtained through Venny 2.1.0. The related protein interaction network was constructed with the STRING database, and topology analysis was performed through CytoNCA. GO biological function analysis and KEGG enrichment analysis for core targets were performed through the ClueGO. Results : Network analysis identified 126 compounds in five herbal medicines of Yijin-tang. Among them, 15 compounds(naringenin, beta-sitosterol, stigmasterol, baicalein, baicalin, calycosin, dihydrocapsaicin, formononetin, glabridin, isorhamnetin, kaempferol, mairin, quercetin, sitosterol, nobiletin) were the key chemicals. The target proteins were 119, and 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were linked to Meniere's disease-related genes. Core genes in this network were TNF, CASP9, and NOS2. GO/KEGG pathway analysis results indicate that these targets are primarily involved in regulating biological processes, such as excitotoxicity, oxidative stress, and apoptosis. Conclusion : Pharmacological network analysis can help to explain the applicability of Yijin-tang on Meniere's disease.
E. S. Choung;S. Y. Eom;Kim, J. H.;Kim, K. S.;Kim, K. H.;Lee, K. G.;Lee, Y. W.;C. S. Cho
Proceedings of the SCSK Conference
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2003.09a
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pp.501-519
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2003
Silk Sericin(SS) is a natural protein extracted from cocoon of bombix mori and shows moisturizing effect to the skin due to a number of hydroxyl groups in the structure. But its application to cosmetics is limited due to its poor solubility in water. In order to solve this drawback and expand its application to cosmetics, polyethyleneglycol(PEG) was conjugated with sericin by reacting activated polyethyleneglycol(ActPEG). Reaction site of sericin is tyrosine residue, which was determined by using $^1$H-NMR. Random coil structure of sericin was transformed to beta-sheet structure by conjugating polyethyleneglycol. It was confirmed that melting point of sericin-PEG conjugate was lowered compared to that of each sericin and PEG due to the interaction between sericin and PEG in crystalline structure. Self-assembled sericin-PEG nanoparticle was obtained by dialyzing with alcohol solution of sericin-PEG conjugate against water. The particle is spherical and has 200-400nm of size. The moisturizing ability of sericin-PEG nanoparticle was much higher than that of sericin itself. Incorporation of vitamin A into sericin-PEG nanoparticle was carried out by diafiltration method. The content of incorporated Vitamin A in sericin-PEG nanoparticle was 8.9 wt%. Releasing behaviour of vitamin A incorporated into nanoparticle was tested in phosphate buffer, pH 7.4 at 37$^{\circ}C$. and half-life of Vitamin A release was 43hrs. Sericin-PEG nanoparticle exhibited higher moisturing effect than sericin itself and distilled water, respectively. No toxicity and irritation were observed in animal tests. It can be expected that the self-assembled sericin-PEG nanoparticle can be developed for cosmetics.
Jae Hyeong Lee;Sang-Ah Park;Il-Geun Park;Bo Kyung Yoon;Jung-Shin Lee;Ji Min Lee
Molecules and Cells
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v.46
no.8
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pp.476-485
/
2023
Gastric cancer stem-like cells (GCSCs) possess stem cell properties, such as self-renewal and tumorigenicity, which are known to induce high chemoresistance and metastasis. These characteristics of GCSCs are further enhanced by autophagy, worsening the prognosis of patients. Currently, the mechanisms involved in the induction of stemness in GCSCs during autophagy remain unclear. In this study, we compared the cellular responses of GCSCs with those of gastric cancer intestinal cells (GCICs) whose stemness is not induced by autophagy. In response to glucose starvation, the levels of β-catenin and stemness-related genes were upregulated in GCSCs, while the levels of β-catenin declined in GCICs. The pattern of deubiquitinase ubiquitin C-terminal hydrolase-L3 (UCH-L3) expression in GCSCs and GCICs was similar to that of β-catenin expression depending on glucose deprivation. We also observed that inhibition of UCH-L3 activity reduced β-catenin protein levels. The interaction between UCH-L3 and β-catenin proteins was confirmed, and it reduced the ubiquitination of β-catenin. Our results suggest that UCH-L3 induces the stabilization of β-catenin, which is required to promote stemness during autophagy activation. Also, UCH-L3 expression was regulated by c-Fos, and the levels of c-Fos increased in response to autophagy activation. In summary, our findings suggest that the inhibition of UCH-L3 during nutrient deprivation could suppress stress resistance of GCSCs and increase the survival rates of gastric cancer patients.
Luis Felipe Guzman;Guillermo Martinez-Velazquez;Fernando Villasenor-Gonzalez;Vicente Eliezer Vega-Murillo;Jose Antonio Palacios-Franquez;Angel Rios-Utrera;Moises Montano-Bermudez
Animal Bioscience
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v.36
no.5
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pp.704-709
/
2023
Objective: In tropical, subtropical and arid zones, heat stress is the main cause of productivity reduction in cattle. When climate stressors occur, animals become thermal adapted through differential expression of some genes, including heat shock proteins (HSP) family. The aim of this study was to determine levels of expression of HSP60, HSP70, and HSP90 genes in Simmental cattle raised in tropical environments of Mexico. Methods: In this study, expression of HSP60, HSP70, and HSP90 genes was analyzed in 116 Simmental cattle from three farms with tropical climate located in western Mexico. Animals were sampled twice a day, in the morning and noon. Gene expression was evaluated by quantitative polymerase chain reaction using probes marked with fluorescence. The MIXED procedure of SAS with repeated measures was used for all statistical analysis. Results: HSP60 gene expression differences were found for sex (p = 0.0349). HSP70 gene differences were detected for sampling hour (p = 0.0042), farm (p<0.0001), sex (p = 0.0476), and the interaction sampling hour×farm (p = 0.0002). Gene expression differences for HSP90 were observed for farm (p<0.0001) and year (p = 0.0521). HSP70 gene showed to be a better marker of heat stress than HSP60 and HSP90 genes. Conclusion: Expression of HSP70 gene in Simmental herds of the tropical region of western México was different during early morning and noon, but the expression of the HSP60 and HSP90 genes was similar. Identification of resilient animals to heat stress will be useful in the genetic improvement of the Simmental breed.
Zichao Tan;Chuanfeng Zhou;Xueping Shi;Lihua Wang;Shubai Wang
Animal Bioscience
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v.36
no.5
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pp.731-739
/
2023
Objective: This study was to evaluate the interaction of three different light-emitting diode (LED) light colors (white, green, and blue) and three intensities (5, 10, and 15 lx) on slaughter performance, meat quality and serum antioxidant capacity of broilers raised in three-layer cages. Methods: A total of 648 (8-days-old) male broiler chicks (Cobb-500) were randomly assigned in 3×3 factorially arranged treatments: three light colors (specifically, white, blue, and green) and three light intensities (namely, 5, 10, and 15 lx) for 35 days. Each treatment consisted of 6 replicates of 12 chicks. The test lasted for 35 days. Results: The semi-eviscerated weight percentage (SEWP) in 5 lx white was higher than that in 15 lx (p<0.01). The eviscerated weight percentage (EWP) (p<0.05) and water-loss percentage (WLP) (p<0.01) decreased in 10 lx white light than those in green light. Under blue light, the content of hypoxanthine (Hx) in muscle was lower than that under white and green light (p<0.01). The content of malondialdehyde (MDA) in 15 lx blue light was higher than that in 10 lx green light (p<0.05). Light color had an extremely significant effect on thigh muscle percentage, WLP, Hx, and crude protein content (p<0.01). Light intensity had a significant effect on SEWP (p<0.05), EWP (p<0.05), lightness (L*) value (p<0.05), WLP (p<0.01), and the contents of superoxide dismutase (p<0.05), MDA (p<0.01), glutathione peroxidase (p<0.01). Conclusion: Using white LED light with 10 lx light intensity can significantly improve the chicken quality of caged Cobb broilers, improve the content of inosine acid in chicken breast and enhance the antioxidant capacity of the body. We suggest that the broiler farm can use 10 lx white LED light source for lighting in 8 to 42 days.
Thanh T. Nguyen;Shola G. Olumodeji;Kirsty L. Chidgey;Timothy J. Wester;Carolina E. Realini;Patrick C. H. Morel
Animal Bioscience
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v.36
no.7
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pp.1091-1100
/
2023
Objective: The present study is to examine the effect of high inclusion of co-products in pig diets (referred to as an alternative diet) during the finishing stage on pig growth performance, meat quality and boar taint compounds. Methods: Growing pigs were fed an alternative diet made with distillers dried grains with solubles (25%), canola meal (20%), and wheat middling (15%) or a control diet based on barley and soybean meal to investigate the impact of co-products on pig performance and meat quality. Sixteen female and sixteen entire male Duroc×(Large White×Landrace) pigs (22.6±2.07 kg, body weight±standard error) were equally allocated to the diets. Results: Pigs fed the alternative diet had a lower feed intake; however, growth rate and feed conversion efficiency were unaffected by diet. A diet by sex interaction was found for gain:feed whereby males fed the alternative diet had the best feed conversion (p<0.01). Pork from pigs fed the alternative diet had lower a* and Chroma and protein % (p<0.05), while other meat quality characteristics were unaffected. The alternative diet reduced backfat skatole levels (p<0.001). Conclusion: A diet containing high inclusion levels of co-products can be fed to pigs during the finishing stage without detrimental effects on pig performance or meat quality and with the potential to enhance pork flavour. This finding suggests a solution to increase the sustainable development of pig production.
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