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On page 1 showing 1 ~ 12 papers out of 12 papers

Transcriptome analysis of methyl jasmonate-elicited Panax ginseng adventitious roots to discover putative ginsenoside biosynthesis and transport genes.

  • Hongzhe Cao‎ et al.
  • International journal of molecular sciences‎
  • 2015‎

The Panax ginseng C.A. Meyer belonging to the Araliaceae has long been used as an herbal medicine. Although public databases are presently available for this family, no methyl jasmonate (MeJA) elicited transcriptomic information was previously reported on this species, with the exception of a few expressed sequence tags (ESTs) using the traditional Sanger method. Here, approximately 53 million clean reads of adventitious root transcriptome were separately filtered via Illumina HiSeq™2000 from two samples treated with MeJA (Pg-MeJA) and equal volumes of solvent, ethanol (Pg-Con). Jointly, a total of 71,095 all-unigenes from both samples were assembled and annotated, and based on sequence similarity search with known proteins, a total of 56,668 unigenes was obtained. Out of these annotated unigenes, 54,920 were assigned to the NCBI non-redundant protein (Nr) database, 35,448 to the Swiss-prot database, 43,051 to gene ontology (GO), and 19,986 to clusters of orthologous groups (COG). Searching in the Kyoto encyclopedia of genes and genomes (KEGG) pathway database indicated that 32,200 unigenes were mapped to 128 KEGG pathways. Moreover, we obtained several genes showing a wide range of expression levels. We also identified a total of 749 ginsenoside biosynthetic enzyme genes and 12 promising pleiotropic drug resistance (PDR) genes related to ginsenoside transport.


Thalidomide Alleviates Pulmonary Fibrosis Induced by Silica in Mice by Inhibiting ER Stress and the TLR4-NF-κB Pathway.

  • Yaqian Li‎ et al.
  • International journal of molecular sciences‎
  • 2022‎

Silicosis is the most prevalent occupational disease in China. It is a form of pulmonary fibrosis caused by the inhalation of silicon particles. As there is no cure for the potentially lethal and progressive condition, the treatment of silicotic fibrosis is an important and difficult problem to address. Thalidomide, a drug with anti-inflammatory and immunoregulatory properties, has been reported to have lung-protective effects. The purpose of this study was to observe the therapeutic effect of thalidomide on silicotic mice and to determine the protective mechanism. By using silicotic mice models and MH-S cells, we found the expression of endoplasmic reticulum stress (ER stress) and Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) pathway as well as inflammation-related factors were upregulated in the macrophages of silicotic mice. The same indexes were detected in silica-stimulated MH-S cells, and the results were consistent with those in vivo. That is, silica activated ER stress and the TLR4-NF-κB pathway as well as the inflammatory response in vitro. Treating both silicotic mice and silica-stimulated MH-S cells with thalidomide inhibited ER stress and the TLR4-NF-κB pathway as well as the inflammatory response. The present study demonstrates thalidomide as a potential therapeutic agent against silicosis.


Protein Expression Profile in Rat Silicosis Model Reveals Upregulation of PTPN2 and Its Inhibitory Effect on Epithelial-Mesenchymal Transition by Dephosphorylation of STAT3.

  • Ying Zhu‎ et al.
  • International journal of molecular sciences‎
  • 2020‎

Silicosis is a chronic occupational lung disease caused by long-term inhalation ofcrystalline silica particulates. We created a rat model that closely approximates the exposure and development of silicosis in humans. Isobaric tags for relative and absolute quantitation (iTRAQ) technologies weused to identify proteins differentially expressed in activated rat lung tissue. We constructed three lentiviral knockdown vectorsand an overexpression vectorfor the protein tyrosine phosphatase non-receptor type 2 (PTPN2) geneto achieve stable long-term expression.A total of 471 proteins were differentially expressed in the silicosis group compared with controls. Twenty upregulated, and eight downregulated proteins exhibited a ≥ 1.5-fold change relative to controls. We next found that the PTPN2, Factor B, and VRK1 concentrations in silicotic rats silicosis and SiO2-stimulated MLE-12 cells were significantly higher than control groups.More importantly, we found that overexpression of PTPN2 simultaneously decreased the expression of phospho-signal transducer and activator of transcription 3 (p-STAT3) and Vimentin, while increasing E-cadherin expression. The opposite pattern was observed for PTPN2-gene silencing. We identified three proteins with substantially enhanced expression in silicosis. Our study also showed that PTPN2 can inhibit epithelial-mesenchymal transition by dephosphorylating STAT3 in silicosis fibrosis.


Effect of Sex Differences in Silicotic Mice.

  • Fuyu Jin‎ et al.
  • International journal of molecular sciences‎
  • 2022‎

Mechanisms of silicosis, caused by the inhalation of silica are still unclear, and the effect of sex on silicosis has rarely been reported. The purpose of this study was to investigate whether sex affects the silicotic lesions and the progressive fibrotic responses in silicosis. Our study showed that sex had no significant effect on the area of silicon nodules and the collagen deposition after a one-time bronchial perfusion of silica. Immunohistochemical staining showed that CD68 and the transforming growth factor-β1 (TGF-β1) were positive in male and female silicotic mice. In addition, the western blot results showed that the fibrosis-related factors type I collagen (COL I), α-smooth muscle actin (α-SMA), vimentin, TGF-β1, p-SMAD2/3, inflammatory-related factors interleukin 6 (IL 6), interleukin 1β (IL 1β), and senescence-related factors p16 and p21 were up-regulated in silicotic mice and there was no difference between female or male mice exposed to silica. The expression of TGF-β1, p-SMAD2/3, p16, and p21 were downregulated in the early stage of female silicotic mice, compared to the males. Thus, despite differences in the expression of certain factors, there was no overall difference in the progressive fibrosis between female and male mice in silicosis. These results thus provide a new perspective for studying the pathological development of silicosis.


Oxamate Attenuates Glycolysis and ER Stress in Silicotic Mice.

  • Na Mao‎ et al.
  • International journal of molecular sciences‎
  • 2022‎

Glycolysis and ER stress have been considered important drivers of pulmonary fibrosis. However, it is not clear whether glycolysis and ER stress are interconnected and if those interconnections regulate the development of pulmonary fibrosis. Our previous studies found that the expression of LDHA, a key enzyme involved in glycolysis, was increased in silica-induced macrophages and silicotic models, and it was closely related to silicosis fibrosis by participating in inflammatory response. However, whether pharmacological inhibition of LDHA is beneficial to the amelioration of silicosis fibrosis remains unclear. In this study, we investigated the effects of oxamate, a potent inhibitor of LDHA, on the regulation of glycolysis and ER stress in alveolar macrophages and silicotic mice. We found that silica induced the upregulation of glycolysis and the expression of key enzymes directly involved in ER stress in NR8383 macrophages. However, treatment of the macrophages and silicotic mice with oxamate attenuated glycolysis and ER stress by inhibiting LDHA, causing a decrease in the production of lactate. Therefore, oxamate demonstrated an anti-fibrotic role by reducing glycolysis and ER stress in silicotic mice.


Genome-Wide Identification and Analysis of the Metallothionein Genes in Oryza Genus.

  • Mingxing Cheng‎ et al.
  • International journal of molecular sciences‎
  • 2021‎

Metallothionein (MT) proteins are low molecular mass, cysteine-rich, and metal-binding proteins that play an important role in maintaining metal homeostasis and stress response. However, the evolutionary relationships and functional differentiation of MT in the Oryza genus remain unclear. Here we identified 53 MT genes from six Oryza genera, including O. sativa ssp. japonica, O. rufipogon, O. sativa ssp. indica, O. nivara, O. glumaepatula, and O. barthii. The MT genes were clustered into four groups based on phylogenetic analysis. MT genes are unevenly distributed on chromosomes; almost half of the MT genes were clustered on chromosome 12, which may result from a fragment duplication containing the MT genes on chromosome 12. Five pairs of segmental duplication events and ten pairs of tandem duplication events were found in the rice MT family. The Ka/Ks values of the fifteen duplicated MT genes indicated that the duplicated MT genes were under a strong negative selection during evolution. Next, combining the promoter activity assay with gene expression analysis revealed different expression patterns of MT genes. In addition, the expression of OsMT genes was induced under different stresses, including NaCl, CdCl2, ABA, and MeJ treatments. Additionally, we found that OsMT genes were mainly located in chloroplasts. These results imply that OsMT genes play different roles in response to these stresses. All results provide important insights into the evolution of the MT gene family in the Oryza genus, and will be helpful to further study the function of MT genes.


Association between phosphatase related gene variants and coronary artery disease: case-control study and meta-analysis.

  • Xia Han‎ et al.
  • International journal of molecular sciences‎
  • 2014‎

Recent studies showed that the serum alkaline phosphatase is an independent predictor of the coronary artery disease (CAD). In this work, we aimed to summarize the association between three phosphatase related single nucleotide polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This significant association of rs3828329 with CAD was only found in the females (Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03; recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p < 0.0001, random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p < 0.0001, fixed-effects method) were associated with CAD risk in multiple populations. Our results showed that the polymorphisms rs12526453 and rs11066301 are significantly associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene is also a risk factor of CAD in Han Chinese females aged 65 years and older.


Glycolytic Reprogramming in Silica-Induced Lung Macrophages and Silicosis Reversed by Ac-SDKP Treatment.

  • Na Mao‎ et al.
  • International journal of molecular sciences‎
  • 2021‎

Glycolytic reprogramming is an important metabolic feature in the development of pulmonary fibrosis. However, the specific mechanism of glycolysis in silicosis is still not clear. In this study, silicotic models and silica-induced macrophage were used to elucidate the mechanism of glycolysis induced by silica. Expression levels of the key enzymes in glycolysis and macrophage activation indicators were analyzed by Western blot, qRT-PCR, IHC, and IF analyses, and by using a lactate assay kit. We found that silica promotes the expression of the key glycolysis enzymes HK2, PKM2, LDHA, and macrophage activation factors iNOS, TNF-α, Arg-1, IL-10, and MCP1 in silicotic rats and silica-induced NR8383 macrophages. The enhancement of glycolysis and macrophage activation induced by silica was reduced by Ac-SDKP or siRNA-Ldha treatment. This study suggests that Ac-SDKP treatment can inhibit glycolytic reprogramming in silica-induced lung macrophages and silicosis.


A GPAT1 Mutation in Arabidopsis Enhances Plant Height but Impairs Seed Oil Biosynthesis.

  • Yang Bai‎ et al.
  • International journal of molecular sciences‎
  • 2021‎

Glycerol-3-phosphate acyltransferases (GPATs) play an important role in glycerolipid biosynthesis, and are mainly involved in oil production, flower development, and stress response. However, their roles in regulating plant height remain unreported. Here, we report that Arabidopsis GPAT1 is involved in the regulation of plant height. GUS assay and qRT-PCR analysis in Arabidopsis showed that GPAT1 is highly expressed in flowers, siliques, and seeds. A loss of function mutation in GPAT1 was shown to decrease seed yield but increase plant height through enhanced cell length. Transcriptomic and qRT-PCR data revealed that the expression levels of genes related to gibberellin (GA) biosynthesis and signaling, as well as those of cell wall organization and biogenesis, were significantly upregulated. These led to cell length elongation, and thus, an increase in plant height. Together, our data suggest that knockout of GPAT1 impairs glycerolipid metabolism in Arabidopsis, leading to reduced seed yield, but promotes the biosynthesis of GA, which ultimately enhances plant height. This study provides new evidence on the interplay between lipid and hormone metabolism in the regulation of plant height.


Gene Expression Profiling Reveals Potential Players of Left-Right Asymmetry in Female Chicken Gonads.

  • Zhiyi Wan‎ et al.
  • International journal of molecular sciences‎
  • 2017‎

Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was carried out on total RNA harvested from the left and right gonads on embryonic day 6 (E6), E12, and post-hatching day 1 (D1). By comparing the gene expression profiles between the left and right gonads, 347 differentially expressed genes (DEGs) were obtained on E6, 3730 were obtained on E12, and 2787 were obtained on D1. Side-specific genes were primarily derived from the autosome rather than the sex chromosome. Gene ontology and pathway analysis showed that the DEGs were most enriched in the Piwi-interactiing RNA (piRNA) metabolic process, germ plasm, chromatoid body, P granule, neuroactive ligand-receptor interaction, microbial metabolism in diverse environments, and methane metabolism. A total of 111 DEGs, five gene ontology (GO) terms, and three pathways were significantly different between the left and right gonads among all the development stages. We also present the gene number and the percentage within eight development-dependent expression patterns of DEGs in the left and right gonads of female chicken.


Development of a Combined Genetic Engineering Vaccine for Porcine Circovirus Type 2 and Mycoplasma Hyopneumoniae by a Baculovirus Expression System.

  • Yu Tao‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are the main pathogens for mycoplasmal pneumonia of swine (MPS) and post-weaning multisystemic wasting syndrome (PMWS), respectively. Infection by these pathogens often happens together and causes great economic losses. In this study, a kind of recombinant baculovirus that can display P97R1P46P42 chimeric protein of Mhp and the capsid (Cap) protein of PCV2 was developed, and the protein location was identified. Another recombinant baculovirus was constructed without tag proteins (EGFP, mCherry) and was used to evaluate the immune effect in experiments with BALB/c mice and domestic piglets. Antigen proteins P97R1P46P42 and Cap were expressed successfully; both were anchored on the plasma membrane of cells and the viral envelope. It should be emphasized that in piglet immunization, the recombinant baculovirus vaccine achieved similar immunological effects as the mixed commercial vaccine. Both the piglet and mouse experiments showed that the recombinant baculovirus was able to induce humoral and cellular responses effectively. The results of this study indicate that this recombinant baculovirus is a potential candidate for the further development of more effective combined genetic engineering vaccines against MPS and PMWS. This experiment also provides ideas for vaccine development for other concomitant diseases using the baculovirus expression system.


Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K/AKT Pathway.

  • Xiaohui Hao‎ et al.
  • International journal of molecular sciences‎
  • 2023‎

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-β1 (TGF-β1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-β1- and TGF-β1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-β1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.


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