• Asian-Australasian Journal of Animal Sciences
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• v.33 no.2
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• pp.187-196
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• 2020

Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (F_ST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r² = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r² = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Herbal Formula Science
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• v.22 no.1
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• pp.151-165
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• 2014

Objectives : The aim of this study was to evaluate the efficacy of Aconiti Lateralis Preparata Radix (AP) and Acanthopanacis Cortex (AT) extracts in bone-derived adipocyte OP9 cell, osteoclast and osteoblast-like MG63 cells. Methods : MTT assay was used to evaluate the cytotoxicity of AP and AT extracts on OP9, osteoclast and MG63 cells. OP9 cells were treated with AP and AT, and the alterations in fat storage in the cells were determined by the Oil red O. To explain effects of RANKL-induced osteoclast differentiation in bone marrow macrophages, we performed the TRAP staining. The protein level of CAAAT/enhancer binding protein alpha ($C/EBP{\alpha}$) and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) as a adipocyte differentiation marker, and adiponectin was examined using western blot in differentiated OP9 cells. Effects of related genes were confirmed by luciferase assay using reporter assay. Results : AP and AT was not toxic on OP9 and MG63 cells, but AT was a little cytotoxic to osteoclast at the dose of $100{\mu}g/m{\ell}$. They could inhibit differentiation of OP9 cells and osteoclast with results of oil red O staining and TRAP staining. By western blot, AP and AT decreased the expression of $PPAR{\gamma}$ and $C/EBP{\alpha}$ which is the key transcription factor in adipogenesis and adiponectin secretion. AT also inhibited the BMP-4 activity in luciferase assay. AP also inhibited BMP-4 and Wnt3a activity, stimulated ER-${\beta}$ activity but inhibited androgen receptor activity. Conclusions : These results show AP and AT can be useful in osteoporosis and obesity via inhibition of osteoclast and adipocyte differentiation.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.247-257
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• 2022

Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions: Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our understanding of the importance of RA signaling in the differentiation of hiPSC-CMs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.54-63
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• 2010

Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

• Journal of Life Science
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• v.20 no.7
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• pp.1054-1065
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• 2010

SH21B is a natural composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). In our previous study, we reported that SH21B inhibited adipogenesis and fat accumulation in 3T3-L1 cells through modulation of various regulators in the adipogenesis pathway. The aim of this study was to analyze the transcriptome profiles for the anti-adipogenic effects of SH21B in 3T3-L1 cells. Total RNAs from SH21B-treated 3T3-L1 cells were reverse-transcribed into cDNAs and hybridized to Affymetrix Mouse Gene 1.0 ST array. From microarray analyses, we identified 2,568 genes of which expressions were changed more than two-fold by SH21B, and the clustering analyses of these genes resulted in 9 clusters. Three clusters among the 9 showed down-regulation by SH21B (cluster 4, cluster 6 and cluster 9), and two clusters showed up-regulation by SH21B (cluster 7 and cluster 8) during the adipogenesis of 3T3-L1 cells. It was found that many genes related to cell proliferation and adipogenesis were included in these clusters. Clusters 4, 6 and 9 included genes which were related with adipogenesis induction and cell cycle arrest. Clusters 7 and 8 included genes related to cell proliferation as well as adipogenesis inhibition. These results suggest that the mechanisms of the anti-adipogenic effects of SH21B may be the modulation of genes involved in cell proliferation and adipogenesis.