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2021 ◽  
Author(s):  
Bing Wang ◽  
Qian Feng ◽  
chao zhang ◽  
Yuming Chen ◽  
Yu Chen ◽  
...  

Abstract Background Astragali Radix (AR),the dried root of legumes, belongs to the Qi- invigorating herbs in traditional Chinese medicine and plays an important role in the treatment of many diseases. In order to understand the mechanism of action of AR extract, we used AR extract to treat M-1, mouse kidney cells, and used transcriptome sequencing technology to detect the genomic transcription level of the cells under the action of AR at different concentrations and times. Result The results showed that after a low concentration of AR treatments on the cells, the expression of genes related to cell growth and cellular immune response changed significantly, among which multiple genes are related to mitochondrial function, while high concentrations of AR affected the expression of histones and disease-related genes. It showed that the low concentration of AR extract can achieve the effect of invigorating Qi by regulating the function of mitochondria. In addition, several important genes and pathways were identified as potential targets of AR activation. Conclusion The research not only clarified the main molecular biological mechanism of AR invigorating Qi, but also provided experimental basis and cellular physiology reference for the further clinical application of AR.


2021 ◽  
Author(s):  
Hui Song ◽  
Feng Chen ◽  
Xi Wu ◽  
Min Hu ◽  
Qingliu Geng ◽  
...  

Abstract Abstract Iron (Fe) is an indispensable mineral element for normal growth of plants. Fe deficiency induces a complex series of responses in plants, involving physiological and developmental changes, to increase Fe uptake from soil. However, the molecular mechanism involved in plant Fe-deficiency is not well understood. Here, we found that the MNB1 gene is involved in modulating Fe-deficiency response in Arabidopsis thaliana . The expression of MNB1 was inhabited by Fe-deficiency stress. Knockout of MNB1 led to enhanced Fe accumulation and tolerance, whereas the MNB1-overexpressing plants were sensitive to Fe-deficiency stress. Lower H 2 O 2 concentrations in mnb1 mutant plants were examined under Fe deficiency circumstances compared to wild-type. On the contray, higher H 2 O 2 concentrations were found in MNB1-overexpressing plants, which was adversely linked with malondialdehyde (MDA) concentrations. Furthermore, in mnb1 mutants, the transcription level of the Fe-uptake and translocation genes, FIT , IRT1 , FRO2 , Z IF , FRD3 , NAS4 , PYE and MYB72 , were considerably elevated during Fe-deficiency stress, resulting in higher Fe accumulation. Together, our findings show that the MNB1 gene negatively controls the Fe-deficiency response in Arabidopsis via modulating reactive oxygen species (ROS) levels and the ROS-mediated signaling pathway, thereby affecting the expression of Fe-uptake and translocation genes.


Author(s):  
Niloofar Rashidi ◽  
Sassan Rezaie ◽  
Sayed Jamal Hashemi ◽  
Aziziollah Habibi ◽  
Mohammad Hadi Baghersad ◽  
...  

Background: Candida albicans remains the main cause of candidiasis in most clinical settings. Available drugs for candidiasis treatment have many side effects. In this work, novel nitroglycerin derivatives were synthesized and their cytotoxic and antifungal effects evaluated against fluconazole susceptible and resistant clinical C. albicans isolates. Methods: This experimental study was performed in Tehran University of Medical Sciences and Baqiatallah University of Medical Sciences, Tehran, Iran between Feb to Dec 2019. The in vitro activities of two novel nitroglycerin derivatives (1b and 2b) against 25 clinical fluconazole-susceptible and resistant C. albicans isolates and four standard C. albicans strains were determined according to CLSI reference M27-A3 documents. The cytotoxicity of chemical compounds was investigated near the SNL76/7 cells by colorimetric assay. Real-time PCRs were performed to evaluate the alterations in the regulation of ERG11 and CDR1 genes under nitroglycerin derivatives-treated and untreated conditions. Results: The derivatives 1b and 2b exhibited potent antifungal activity against C. albicans isolates; MICs and MFCs varied from 18 μg/ml to 72 μg/ml and 36 μg/ml to 144 μg/ml, respectively. The cell viability evaluation demonstrated that both chemical compounds are safe within 24h. The nitroglycerin derivatives were able to reduce the transcription level of CDR1 and ERG11 genes in all susceptible and resistant C. albicans isolates. Conclusion: Considering the potential and efficacy of these compounds against clinical C. albicans isolates, the complementary in vivo and clinical trials should be investigated.


2021 ◽  
Vol 22 (17) ◽  
pp. 9568
Author(s):  
Yong Zhang ◽  
Jun Liu ◽  
Jingjin Yu ◽  
Huangwei Zhang ◽  
Zhimin Yang

Seashore paspalum is a major warm-season turfgrass requiring frequent mowing. The use of dwarf cultivars with slow growth is a promising method to decrease mowing frequency. The present study was conducted to provide an in-depth understanding of the molecular mechanism of T51 dwarfing in the phenylpropane pathway and to screen the key genes related to dwarfing. For this purpose, we obtained transcriptomic information based on RNA-Seq and proteomic information based on iTRAQ for the dwarf mutant T51 of seashore paspalum. The combined results of transcriptomic and proteomic analysis were used to identify the differential expression pattern of genes at the translational and transcriptional levels. A total of 8311 DEGs were detected at the transcription level, of which 2540 were upregulated and 5771 were downregulated. Based on the transcripts, 2910 proteins were identified using iTRAQ, of which 392 (155 upregulated and 237 downregulated) were DEPs. The phenylpropane pathway was found to be significantly enriched at both the transcriptional and translational levels. Combined with the decrease in lignin content and the increase in flavonoid content in T51, we found that the dwarf phenotype of T51 is closely related to the abnormal synthesis of lignin and flavonoids in the phenylpropane pathway. CCR and HCT may be the key genes for T51 dwarf. This study provides the basis for further study on the dwarfing mechanism of seashore paspalum. The screening of key genes lays a foundation for further studies on the molecular mechanism of seashore paspalum dwarfing.


2021 ◽  
Author(s):  
Liang Chen ◽  
Genghong Lin ◽  
Feng Jiao

Gene activation is usually a non-Markovian process that has been modeled as various frameworks that consist of multiple rate-limiting steps. Understanding the exact activation framework for a gene of interest is a central problem for single-cell studies. In this paper, we focus on the dynamical data of the average transcription level M(t), which is typically neglected when deciphering gene activation. Firstly, the smooth trend lines of M(t) data present rich, visually dynamic features. Secondly, tractable analysis of M(t) allows the establishment of bijections between M(t) dynamics and system parameter regions. Because of these two clear advantages, we can rule out frameworks that fail to capture M(t) features and we can further test potential competent frameworks by fitting M(t) data. We implemented this procedure to determine an exact activation framework for a large number of mouse fibroblast genes under tumor necrosis factor induction; the cross-talk between the signaling and basal pathways is crucial to trigger the first peak of M(t), while the following damped gentle M(t) oscillation is regulated by the multi-step basal pathway. Moreover, the fitted parameters for the mouse genes tested revealed two distinct regulation scenarios for transcription dynamics. Taken together, we were able to develop an efficient procedure for using traditional M(t) data to estimate the gene activation frameworks and system parameters. This procedure, together with sophisticated single-cell transcription data, may facilitate a more accurate understanding of stochastic gene activation.


2021 ◽  
Author(s):  
Tong Qin ◽  
Yunli Shao ◽  
Hongmian Zhao

Abstract BackgroundIn recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in patients with AML have not been fully elucidated.ResultsWe found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high transcription level of STAT6 was associated with low overall survival (OS) in patients with AML. Conversely, high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML.ConclusionsSTAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.


2021 ◽  
Author(s):  
Reji Manjunathan ◽  
Vijayalakshmi Periyaswami ◽  
Malathi Ragunathan

Abstract Background - High-molecular weight heparin (HMWH), a molecule which is extensively in use as an anticoagulant shows concentration-dependent angiogenic and anti-angiogenic potential. Based on the concentration, HMWH can bind with both angiogenic and anti-angiogenic factors and exerts diverse effect. Our earlier data suggested that HMWH (15 kDa) can induce concentration-dependent neovascularization on chicken chorioallantoic membrane (CAM). The diffusion pattern of HMWH through various layers of CAM supports its internalized action with the various cellular components of angiogenesis. So far, no studies have reported the interactive potential of HMWH with various pro-angiogenic growth factors under physiological conditions. Hence, we aimed to find the transcription level interaction of HMWH with major pro-angiogenic growth factors. In connection to the research, for the first time, we validated the three-dimensional structures of chicken-specific pro-angiogenic growth factors such as FGF2, MMP2, MMP9, NOS3, VEGF A, and VEGF C to find the binding affinity of HMWH with the core-functional units of these growth factors. Methods - CAMs are incubated with 50, 100, and 150 µM concentration of HMWH. Changes in the transcription level of specified pro-angiogenic growth factors are analyzed by semi-PCR method. The functional aspects of these molecules are identified with zymogram and immunohistochemical approaches. Scanning electron microscopic technique is applied to find the morphological changes on CAM under HMWH incubation. Three-dimensional structure validation and molecular docking are performed using the SWISS-MODEL web server and AutoDock vina-PyRx software version 8.0. Results - HMWH can enhance the transcription level of major pro-angiogenic growth factors with a significant impact on FGF2 and MMP2 under 100 µM concentration. The in-silico analysis reveals that HMWH shows a higher binding affinity with FGF2 followed by MMP2, MMP9, NOS3, VEGF A, and VEGF C, respectively. Conclusion - The combined results from the experimental and in-silico analysis reveal that HMWH can interact with pro-angiogenic growth factors under micromolar concentration in physiological conditions while inducing angiogenesis. This observation further supports the therapeutic benefits of HMWH as an angiogenic factor under micromolar concentration.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Yang Yu ◽  
Guo-Xia Dou ◽  
Xing-Xing Sun ◽  
Lin Chen ◽  
Ying Zheng ◽  
...  

Postharvest strawberry is susceptible to gray mold disease caused by Botrytis cinerea, which seriously damage the storage capacity of fruits. Biological control has been implicated as an effective and safe method to suppress plant disease. The aim of this study is to evaluate the postharvest disease control ability of Bacillus cereus AR156 and explore the response of strawberry fruit to this biocontrol microorganism. Bacillus cereus AR156 treatment significantly suppressed gray mold disease and postponed the strawberry senescence during storage. The bacterium pretreatment remarkably enhanced the reactive oxygen-scavenging and defense-related activities of enzymes. The promotion on the expression of the encoding-genes was confirmed by quantitative real-time PCR (qRT-PCR) that significantly increased the expression of the marker genes of salicylic acid (SA) signaling pathway, such as PR1, PR2, and PR5, instead of that of the jasmonic acid (JA)/ethylene (ET) pathway, which was also shown. Moreover, through transcriptome profiling, about 6,781 differentially expressed genes (DEGS) in strawberry upon AR156 treatment were identified. The gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicated that AR156 altered the transcription of numerous transcription factors and genes involved in the SA-related plant disease resistance, metabolism, and biosynthesis of benzoxazinoids and flavonoids. This study offered a non-antagonistic Bacillus as a method for postharvest strawberry storage and disease control, and further revealed that the biocontrol effects were arisen from the induction of host responses on the transcription level and subsequent resistance-related substance accumulation.


Insects ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 712
Author(s):  
Jin-Zhi Chen ◽  
Ying-Xia Jiang ◽  
Miao-Wen Li ◽  
Jian-Wen Li ◽  
Ben-Hu Zha ◽  
...  

DsRNA-degrading enzymes (dsRNases) have been recognized as important factors in reducing RNA interference (RNAi) efficiency in different insect species. However, dsRNases in Plutella xylostella are still unknown. We identified the full-length cDNAs of PxdsRNase1, PxdsRNase2, PxdsRNase3, and PxdsRNase4. Gene expression profile showed that PxdsRNase1 was mainly expressed in the hemolymph; and that PxdsRNase2 and PxdsRNase3 were mainly expressed in the intestinal tract. The expression of PxCht (Chitinase of P. xylostella) in P. xylostella larvae injected with the mixture of dsPxCht (dsRNA of PxCht) and dsPxdsRNase1 (dsRNA of PxdsRNase1), dsPxdsRNase2 (dsRNA of PxdsRNase2), or dsPxdsRNase3 (dsRNA of PxdsRNase3) was significantly higher than that in the larvae injected with the mixture of dsGFP (dsRNA of green fluorescent protein gene, GFP) and dsPxCht; the transcription level of PxCht in the larvae feeding on the mixture of dsPxCht and dsPxdsRNase1, dsPxdsRNase2, or dsPxdsRNase3 was significantly higher than that in the larvae feeding on the mixture of dsPxCht and dsGFP. The recombinant protein of PxdsRNase1 degraded dsRNA rapidly, PxdsRNase3 cleaved dsRNA without complete degradation, and PxdsRNase2 could not degrade dsRNA in vitro. These results suggested that PxdsRNases1, PxdsRNases2, and PxdsRNases3 were involved in the dsRNA degradation to reduce RNAi efficiency with different mechanisms.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1554
Author(s):  
Guang-Zhou Zhou ◽  
Jun Li ◽  
Yan-He Sun ◽  
Qin Zhang ◽  
Lu Zhang ◽  
...  

Autophagy and apoptosis are two key cell fate determination pathways, which play vital roles in the interaction between viruses and host cells. Previous research had confirmed that one strain of fish rhabdoviruses, Siniperca chuatsi rhabdovirus (SCRV), could induce apoptosis and autophagy after infection. In the current study, we continued to analyze the interaction of autophagy and apoptosis in SCRV-infected EPC cell lines after treatment with different autophagy or apoptosis inhibitors. We found that SCRV infection could activate the mitochondrial apoptotic pathway by the detection of the activities of the caspase-3 and caspase-9 and by flow cytometry analysis in JC-1-stained cells, respectively. Furthermore, no significant autophagy-related factors were disturbed in SCRV-infected cell after apoptosis inhibitor Z-VAD-FMK treatment, while autophagy inducer rapamycin could obviously delay the occurrence of CPE and cell death. Meanwhile, rapamycin was able to reduce the proportion of apoptotic cells. Besides that, rapamycin could disturb the expression of p62 and LC3B-II, and the transcription level of SCRV nucleoprotein mRNA. The progeny virus titers did not show a big difference between the rapamycin treatment or without it. Collectively, our data preliminarily confirmed that SCRV-activated autophagy could delay apoptosis in EPC cells and may not affect virus production. Further study may need to focus on the crosstalk regulation and its roles on the SCRV infection.


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