Differential Expression Patterns of Glycolytic Enzymes and Mitochondria-Dependent Apoptosis in PCOS Patients with Endometrial Hyperplasia, an Early Hallmark of Endometrial Cancer, In Vivo and the Impact of Metformin In Vitro

Although a number of genes have been found to have restricted expression domains in the embryonic forebrain and midbrain, it remains largely unknown how the expression of these genes is regulated at the cellular level. In this study, we explored the mechanisms for the differential expression of region-specific transcription factors in neuroepithelial cells by using both primary and immortalized neuroepithelial cells from the rat brain at embryonic day 11.5. We found that differential expression patterns of Pax-3, Pax-5, Pax-6, Dlx-1, Dlx-2, Emx2, Otx1 and Dbx observed in vivo were maintained even when the cells were isolated and cultured in vitro, free from environmental influences. Furthermore, in response to Sonic hedgehog, which is a major inductive signal from the environment for regional specification, neuroepithelial cells that maintain distinct regional identities expressed different sets of ventral-specific genes including Islet-1, Nkx-2.1 and Nkx-2.2. These results suggest that certain cell-autonomous mechanisms play important roles in regulating both environmental signal-dependent and -independent expression of region-specific genes. Thus, we propose that use of the in vitro culture systems we describe in this study facilitates the understanding of regulatory mechanisms of region-specific genes in neuroepithelial cells.

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Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy

Frontiers in Oncology ◽

10.3389/fonc.2021.624145 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anna Carrano ◽

Natanael Zarco ◽

Jordan Phillipps ◽

Montserrat Lara-Velazquez ◽

Paola Suarez-Meade ◽

...

Keyword(s):

Gene Expression ◽

Cerebrospinal Fluid ◽

Expression Patterns ◽

Therapeutic Implications ◽

Transcriptional Changes ◽

The Central Nervous System ◽

And Migration ◽

The Impact

Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.

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Gene expression profiling of pluripotency and differentiation-related markers in cat oocytes and preimplantation embryos

Reproduction Fertility and Development ◽

10.1071/rd11068 ◽

2012 ◽

Vol 24 (5) ◽

pp. 691 ◽

Cited By ~ 28

Author(s):

Muriel Filliers ◽

Karen Goossens ◽

Ann Van Soom ◽

Barbara Merlo ◽

Charles Earle Pope ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Preimplantation Development ◽

Gene Expression Patterns ◽

Altered Expression ◽

Transcript Levels ◽

Species Specific ◽

The Impact

During mammalian preimplantation development, two successive differentiation events lead to the establishment of three committed lineages with separate fates: the trophectoderm, the primitive endoderm and the pluripotent epiblast. In the mouse embryo, the molecular mechanisms underlying these two cell fate decisions have been studied extensively, leading to the identification of lineage-specific transcription factors. Species-specific differences in expression patterns of key regulatory genes have been reported, raising questions regarding their role in different species. The aim of the present study was to characterise the gene expression patterns of pluripotency (OCT4, SOX2, NANOG) and differentiation (CDX2, GATA6)-related markers during feline early development using reverse transcription–quantitative polymerase chain reaction. In addition, we assessed the impact of in vitro development on gene expression by comparing transcript levels of the genes investigated between in vitro and in vivo blastocysts. To normalise quantitative data within different preimplantation embryo stages, we first validated a set of stable reference genes. Transcript levels of all genes investigated were present and changed over the course of preimplantation development; a highly significant embryo-stage effect on gene expression was observed. Transcript levels of OCT4 were significantly reduced in in vitro blastocysts compared with their in vivo counterparts. None of the other genes investigated showed altered expression under in vitro conditions. The different gene expression patterns of OCT4, SOX2, CDX2 and GATA6 in cat embryos resembled those described in mouse embryos, indicative of a preserved role for these genes during early segregation. However, because of the absence of any upregulation of NANOG transcription levels after embryonic genome activation, it is unlikely that NANOG is a key regular of lineage segregation. Such results support the hypothesis that the behaviour of early lineage markers can be species specific. The present study also revealed a pool of maternal NANOG mRNA transcripts, the role of which remains to be elucidated. Comparing transcription levels of these genes between in vivo and in vitro blastocysts revealed low levels of OCT4 mRNA in the latter, which may contribute to the reduced developmental competence of embryos under suboptimal conditions.

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Associating gene expressions with curcuminoid biosynthesis in turmeric

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-020-00101-2 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Dipendra Kumar Ayer ◽

Kaushal Modha ◽

Vipulkumar Parekh ◽

Ritesh Patel ◽

Gopal Vadodariya ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Negative Association ◽

Growth Stages ◽

Gene Expressions ◽

Individual Gene ◽

Pharmaceutical Industries ◽

The Impact

Abstract Background Biologically important curcuminoids viz curcumin, demethoxycurcumin, and bisdemethoxycurcumin in turmeric rhizome have several health benefits. Pharmaceutical industries synthesize curcuminoids manipulating gene expressions in vitro or in vivo because of their medicinal importance. In this experiment, we studied the gene expressions involved in the curcuminoid biosynthesis pathway in association with curcuminoid yield in turmeric rhizome to study the impact of individual gene expression on curcuminoid biosynthesis. Results Gene expressions at the different growth stages of turmeric rhizome were association tested with respective curcuminoid contents. Gene expression patterns of diketide-CoA synthase (DCS) and multiple curcumin synthases (CURSs) viz curcumin synthase 1 (CURS1), curcumin synthase 2 (CURS2), and curcumin synthase 3 (CURS3) were differentially associated with different curcuminoid contents. Genotype and growth stages showed a significant effect on the gene expressions resulting in a significant impact on curcuminoid balance in turmeric rhizome. DCS and CURS3 expression patterns were similar but distinct from CURS1 and CURS2 expression patterns in turmeric rhizome. DCS expression had a significant positive and CURS3 expression had a significant negative association with curcumin, demethoxycurcumin, bisdemethoxycurcumin, and total curcuminoid in turmeric rhizome. CURS1 expression had a negative association with curcumin whereas CURS2 expression showed a positive association with demethoxycurcumin. Conclusions The effects of DCS and CURS expressions are not always positive with different curcuminoid contents in turmeric rhizome. DCS expression has a positive and CURS3 expression has a negative association with curcuminoids. CURS1 and CURS2 are also associated with curcumin and demethoxycurcumin synthesis. This mechanism of co-expression of diketide-CoA synthase and multiple curcumin synthases in turmeric rhizome has a significant effect on curcuminoid balance in different turmeric cultivars. Further experiment will explore more insights; however, association-based test results from this experiment can be useful in improving curcuminoid yield in turmeric rhizome or in vitro through the application of genetic engineering and biotechnology. Graphical abstract Associating gene expressions with curcuminoid biosynthesis in turmeric

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The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

Current Drug Targets ◽

10.2174/1389450121666191230145848 ◽

2020 ◽

Vol 21 (7) ◽

pp. 722-734

Author(s):

Adele Soltani ◽

Arefeh Jafarian ◽

Abdolamir Allameh

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Diabetic Control ◽

In Vitro Proliferation ◽

Cell Functions ◽

Mirna Expression Profiles ◽

Multiple Processes ◽

The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

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Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

International Journal of Molecular Sciences ◽

10.3390/ijms20153679 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3679 ◽

Cited By ~ 3

Author(s):

Lin Chen ◽

Alyne Simões ◽

Zujian Chen ◽

Yan Zhao ◽

Xinming Wu ◽

...

Keyword(s):

Wound Healing ◽

Oral Mucosa ◽

Wound Closure ◽

Expression Patterns ◽

Skin Wound ◽

Skin Wound Healing ◽

Specific Expression ◽

Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

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The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

Journal of Ethnopharmacology ◽

10.1016/j.jep.2013.10.003 ◽

2013 ◽

Vol 150 (3) ◽

pp. 1024-1031 ◽

Cited By ~ 35

Author(s):

Mohammad Hossein Boskabady ◽

Sakine Shahmohammadi Mehrjardi ◽

Abadorrahim Rezaee ◽

Houshang Rafatpanah ◽

Sediqeh Jalali

Keyword(s):

Zataria Multiflora ◽

Th2 Cytokine ◽

Ifn Γ ◽

The Impact

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The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-84117-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hiroaki Kanzaki ◽

Tetsuhiro Chiba ◽

Junjie Ao ◽

Keisuke Koroki ◽

Kengo Kanayama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Erk Signaling ◽

Enzyme Linked Immunosorbent Assay ◽

Antitumor Effects ◽

The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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Genome-Wide Transcriptomic Identification and Functional Insight of Lily WRKY Genes Responding to Botrytis Fungal Disease

Plants ◽

10.3390/plants10040776 ◽

2021 ◽

Vol 10 (4) ◽

pp. 776

Author(s):

Shipra Kumari ◽

Bashistha Kumar Kanth ◽

Ju young Ahn ◽

Jong Hwa Kim ◽

Geung-Joo Lee

Keyword(s):

Abiotic Stress ◽

Biotic Stress ◽

Developmental Stages ◽

Expression Patterns ◽

Lilium Longiflorum ◽

Biotic And Abiotic Stress ◽

Biotic Stresses ◽

Genome Wide

Genome-wide transcriptome analysis using RNA-Seq of Lilium longiflorum revealed valuable genes responding to biotic stresses. WRKY transcription factors are regulatory proteins playing essential roles in defense processes under environmental stresses, causing considerable losses in flower quality and production. Thirty-eight WRKY genes were identified from the transcriptomic profile from lily genotypes, exhibiting leaf blight caused by Botrytis elliptica. Lily WRKYs have a highly conserved motif, WRKYGQK, with a common variant, WRKYGKK. Phylogeny of LlWRKYs with homologous genes from other representative plant species classified them into three groups- I, II, and III consisting of seven, 22, and nine genes, respectively. Base on functional annotation, 22 LlWRKY genes were associated with biotic stress, nine with abiotic stress, and seven with others. Sixteen unique LlWRKY were studied to investigate responses to stress conditions using gene expression under biotic and abiotic stress treatments. Five genes—LlWRKY3, LlWRKY4, LlWRKY5, LlWRKY10, and LlWRKY12—were substantially upregulated, proving to be biotic stress-responsive genes in vivo and in vitro conditions. Moreover, the expression patterns of LlWRKY genes varied in response to drought, heat, cold, and different developmental stages or tissues. Overall, our study provides structural and molecular insights into LlWRKY genes for use in the genetic engineering in Lilium against Botrytis disease.

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