Evidence for a shape-based recognition of odorants in vivo in the human nose from an analysis of the molecular mechanism of lily-of-the-valley odorants detection in the Lilial and Bourgeonal family using the C/Si/Ge/Sn switch strategy

Abstract Background Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown. Methods The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). SiRNA or CRISPR-CAS9 were used to silence gene expression. The biological function of circSOD2 in HCC was investigated using in vitro and in vivo studies including, trans-well cell migration, cell apoptosis, cell cycle, CCK8, siRNA interference, western blots, and xenograft mouse model. The underlying molecular mechanism was determined by Chromatin Immunoprecipitation quantitative real time PCR (ChIP-qPCR), bioinformatic analysis, biotin-pull down, RNA immunoprecipitation, 5-mc DNA pulldown and luciferase assays. Results In accordance with previous sequencing results, here, we demonstrated that circSOD2 was highly expressed in HCC tumor tissues compared with normal liver tissues. Mechanically, we showed that histone writer EP300 and WDR5 bind to circSOD2 promoter and trigger its promoter H3K27ac and H3K4me3 modification, respectively, which further activates circSOD2 expression. SiRNA mediated circSOD2 suppression impaired liver cancer cell growth, cell migration, prohibited cell cycle progression and in vivo tumor growth. By acting as a sponge, circSOD2 inhibits miR-502-5p expression and rescues miR-502-5p target gene DNMT3a expression. As a DNA methyltransferase, upregulated DNMA3a suppresses SOCS3 expression by increasing SOCS3 promoter DNA methylation. This event further accelerates SOCS3 downstream JAK2/STAT3 signaling pathway activation. In addition, we also found that activated STAT3 regulates circSOD2 expression in a feedback way. Conclusion The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.

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PGC7 suppresses TET3 for protecting DNA methylation

Nucleic Acids Research ◽

10.1093/nar/gkt1261 ◽

2013 ◽

Vol 42 (5) ◽

pp. 2893-2905 ◽

Cited By ~ 39

Author(s):

Chunjing Bian ◽

Xiaochun Yu

Keyword(s):

Dna Methylation ◽

Molecular Mechanism ◽

Biological Process ◽

Cpg Islands ◽

Binding Motifs ◽

Genome Wide Analysis ◽

Dna Motif ◽

Genome Wide

Abstract Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.

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Numerical simulation of humidification and heating during inspiration within an adult nose

Rhinology Journal ◽

10.4193/rhino11.231 ◽

2012 ◽

Vol 50 (2) ◽

pp. 157-164

Author(s):

F. Sommer ◽

R. Kroger ◽

J. Lindemann

Keyword(s):

Numerical Simulations ◽

High Speed ◽

Middle Turbinate ◽

Multislice Ct ◽

Respiratory Cycle ◽

In Vivo Measurements ◽

Airflow Distribution ◽

The Impact ◽

Human Nose

Background: The temperature of inhaled air is highly relevant for the humidification process. Narrow anatomical conditions limit possibilities for in vivo measurements. Numerical simulations offer a great potential to examine the function of the human nose. Objective: In the present study, the nasal humidification of inhaled air was simulated simultaneously with temperature distribution during a respiratory cycle. Methods: A realistic nose model based on a multislice CT scan was created. The simulation was performed by the Software Fluent(r). Boundary conditions were based on previous in vivo measurements. Inhaled air had a temperature of 20(deg)C and relative humidity of 30%. The wall temperature was assumed to be variable from 34(deg)C to 30(deg)C with constant humidity saturation of 100% during the respiratory cycle. Results: A substantial increase in temperature and humidity can be observed after passing the nasal valve area. Areas with high speed air flow, e.g. the space around the turbinates, show an intensive humidification and heating potential. Inspired air reaches 95% humidity and 28(deg)C within the nasopharynx. Conclusion: The human nose features an enormous humidification and heating capability. Warming and humidification are dependent on each other and show a similar spacial pattern. Concerning the climatisation function, the middle turbinate is of high importance. In contrast to in vivo measurements, numerical simulations can explore the impact of airflow distribution on nasal air conditioning. They are an effective method to investigate nasal pathologies and impacts of surgical procedures.

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Unraveling the Novel Protective Effect of Patchouli Alcohol Against Helicobacter pylori-Induced Gastritis: Insights Into the Molecular Mechanism in vitro and in vivo

Frontiers in Pharmacology ◽

10.3389/fphar.2018.01347 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Da-wei Lian ◽

Yi-fei Xu ◽

Wen-kang Ren ◽

Li-jun Fu ◽

Fang-jun Chen ◽

...

Keyword(s):

Helicobacter Pylori ◽

Protective Effect ◽

Molecular Mechanism ◽

The Novel ◽

Patchouli Alcohol

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Molecular mechanism of L-SP40 peptide and in vivo efficacy against EV-A71 in neonatal mice

Life Sciences ◽

10.1016/j.lfs.2021.120097 ◽

2021 ◽

pp. 120097

Author(s):

Salima Lalani ◽

Soon Hao Tan ◽

Kuan Onn Tan ◽

Hui Xuan Lim ◽

Kien Chai Ong ◽

...

Keyword(s):

Molecular Mechanism ◽

In Vivo Efficacy ◽

Neonatal Mice

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Aplp1 and the Aplp1-Lag3 Complex facilitates transmission of pathologic alpha-synuclein

10.1101/2021.05.01.442157 ◽

2021 ◽

Author(s):

Xiaobo Mao ◽

Hao Gu ◽

Donghoon Kim ◽

Yasuyoshi Kimura ◽

Ning Wang ◽

...

Keyword(s):

Parkinson Disease ◽

Molecular Mechanism ◽

Amyloid Beta ◽

Dopaminergic Neurons ◽

Lymphocyte Activation ◽

Alpha Synuclein ◽

Therapeutic Strategies ◽

Behavioral Deficits ◽

Lymphocyte Activation Gene

Pathologic alpha-synuclein (alpha-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid beta precursor-like protein 1 (Aplp1) forms a complex with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic alpha-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by alpha-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of alpha-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by alpha-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for alpha-syn PFF induced pathology advances our understanding of the molecular mechanism of cell-to-cell transmission of pathologic alpha-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson disease and related alpha-synucleinopathies.

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Coelonin, an Anti-Inflammation Active Component of Bletilla striata and Its Potential Mechanism

International Journal of Molecular Sciences ◽

10.3390/ijms20184422 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4422 ◽

Cited By ~ 5

Author(s):

Fusheng Jiang ◽

Meiya Li ◽

Hongye Wang ◽

Bin Ding ◽

Chunchun Zhang ◽

...

Keyword(s):

Molecular Mechanism ◽

Kinase Inhibitor ◽

Negative Regulator ◽

Antibody Array ◽

Dependent Manner ◽

Active Ingredients ◽

Bletilla Striata ◽

Tnf Α ◽

Anti Inflammatory

Ethanol extract of Bletilla striata has remarkable anti-inflammatory and anti-pulmonary fibrosis activities in the rat silicosis model. However, its active substances and molecular mechanism are still unclear. To uncover the active ingredients and potential molecular mechanism of the Bletilla striata extract, the lipopolysaccharide (LPS)-induced macrophage inflammation model and phospho antibody array were used. Coelonin, a dihydrophenanthrene compound was isolated and identified. It significantly inhibited LPS-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression at 2.5 μg/mL. The microarray data indicate that the phosphorylation levels of 32 proteins in the coelonin pre-treated group were significantly down-regulated. In particular, the phosphorylation levels of the key inflammatory regulators factor nuclear factor-kappa B (NF-κB) were significantly reduced, and the negative regulator phosphatase and tensin homologue on chromosome ten (PTEN) was reduced. Moreover, the phosphorylation level of cyclin dependent kinase inhibitor 1B (p27Kip1), another downstream molecule regulated by PTEN was also reduced significantly. Western blot and confocal microscopy results confirmed that coelonin inhibited LPS-induced PTEN phosphorylation in a dose-dependent manner, then inhibited NF-κB activation and p27Kip1 degradation by regulating the phosphatidylinositol-3-kinases/ v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway negatively. However, PTEN inhibitor co-treatment analysis indicated that the inhibition of IL-1β, IL-6 and TNF-α expression by coelonin was independent of PTEN, whereas the inhibition of p27Kip1 degradation resulted in cell-cycle arrest in the G1 phase, which was dependent on PTEN. The anti-inflammatory activity of coelonin in vivo, which is one of the main active ingredients of Bletilla striata, deserves further study.

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MiR-302b as a Combinatorial Therapeutic Approach to Improve Cisplatin Chemotherapy Efficacy in Human Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers12082261 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2261 ◽

Cited By ~ 1

Author(s):

Alessandra Cataldo ◽

Sandra Romero-Cordoba ◽

Ilaria Plantamura ◽

Giulia Cosentino ◽

Alfredo Hidalgo-Miranda ◽

...

Keyword(s):

Molecular Mechanism ◽

Triple Negative ◽

Standard Of Care ◽

Integrin Subunit ◽

Breast Cancers ◽

Therapeutic Tool ◽

Response To Chemotherapy ◽

Cisplatin Sensitivity

Introduction: Chemotherapy is still the standard of care for triple-negative breast cancers (TNBCs). Here, we investigated miR-302b as a therapeutic tool to enhance cisplatin sensitivity in vivo and unraveled the molecular mechanism. Materials and Methods: TNBC-xenografted mice were treated with miR-302b or control, alone or with cisplatin. Genome-wide transcriptome analysis and independent-validation of Integrin Subunit Alpha 6 (ITGA6) expression was assessed on mice tumor samples. Silencing of ITGA6 was performed to evaluate cisplatin response in vitro. Further, potential transcription factors of ITGA6 (E2F transcription facor 1 (E2F1), E2F transcription factor 2 (E2F2), and Yin Yang 1 (YY1)) were explored to define the miRNA molecular mechanism. The miR-302b expression was also assessed in TNBC patients treated with chemotherapy. Results: The miR–302b-cisplatin combination significantly impaired tumor growth versus the control through indirect ITGA6 downregulation. Indeed, ITGA6 was downmodulated in mice treated with miR-302b–cisplatin, and ITGA6 silencing increased drug sensitivity in TNBC cells. In silico analyses and preclinical assays pointed out the regulatory role of the E2F family and YY1 on ITGA6 expression under miR-302b–cisplatin treatment. Finally, miR-302b enrichment correlated with better overall survival in 118 TNBC patients. Conclusion: MiR-302b can be exploited as a new therapeutic tool to improve the response to chemotherapy, modulating the E2F family, YY1, and ITGA6 expression. Moreover, miR-302b could be defined as a new prognostic factor in TNBC patients.

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Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01742-4 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Mu-Su Pan ◽

Hui Wang ◽

Kamar Hasan Ansari ◽

Xin-Ping Li ◽

Wei Sun ◽

...

Keyword(s):

Tumor Growth ◽

Gallbladder Cancer ◽

Molecular Mechanism ◽

Poor Prognosis ◽

Vasculogenic Mimicry ◽

Tube Formation ◽

Signal Pathway ◽

Cancer Associated Fibroblasts

Abstract Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism. Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (−) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored. Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the upregulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway. Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is overexpressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

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