The characteristic response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes

Domestic cats and other felids rub their faces and heads against catnip (Nepeta cataria) and silver vine (Actinidia polygama) and roll on the ground as a characteristic response. While this response is well known, its biological function and underlying mechanism remain undetermined. Here, we uncover the neurophysiological mechanism and functional outcome of this feline response. We found that the iridoid nepetalactol is the major component of silver vine that elicits this potent response in cats and other felids. Nepetalactol increased plasma β-endorphin levels in cats, while pharmacological inhibition of μ-opioid receptors suppressed the classic rubbing response. Rubbing behavior transfers nepetalactol onto the faces and heads of respondents where it repels the mosquito, Aedes albopictus. Thus, self-anointing behavior helps to protect cats against mosquito bites. The characteristic response of cats to nepetalactol via the μ-opioid system provides an important example of chemical pest defense using plant metabolites in nonhuman mammals.

Download Full-text

TMED3/RPS15A Axis promotes the development and progression of osteosarcoma

Cancer Cell International ◽

10.1186/s12935-021-02340-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wei Xu ◽

Yifan Li ◽

Xiaojian Ye ◽

Yunhan Ji ◽

Yu Chen ◽

...

Keyword(s):

Biological Function ◽

Profile Analysis ◽

Tumor Model ◽

Underlying Mechanism ◽

Molecular Therapy ◽

Loss Of Function ◽

Osteosarcoma Cells ◽

Downstream Target

Abstract Background Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated. Methods The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis. Results The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells. Conclusions In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.

Download Full-text

Cytotoxic Action of Artemisinin and Scopoletin on Planktonic Forms and on Biofilms of Candida Species

Molecules ◽

10.3390/molecules25030476 ◽

2020 ◽

Vol 25 (3) ◽

pp. 476 ◽

Cited By ~ 2

Author(s):

Sourav Das ◽

Lilla Czuni ◽

Viktória Báló ◽

Gábor Papp ◽

Zoltán Gazdag ◽

...

Keyword(s):

Oxidative Stress ◽

Candida Species ◽

Underlying Mechanism ◽

Candida Guilliermondii ◽

Cytotoxic Action ◽

Plant Metabolites ◽

Minimum Effective Concentration ◽

Drug Concentrations ◽

Antifungal Action ◽

Metabolic Activities

We investigated the antifungal activities of purified plant metabolites artemisinin (Ar) and scopoletin (Sc) including inhibition, effects on metabolic activities, viability, and oxidative stress on planktonic forms and on preformed biofilms of seven Candida species. The characteristic minimum inhibitory concentration (MIC90) of Ar and Sc against Candida species ranged from 21.83–142.1 µg/mL and 67.22–119.4 µg/mL, respectively. Drug concentrations causing ≈10% CFU decrease within 60 min of treatments were also determined (minimum effective concentration, MEC10) using 100-fold higher CFUs than in the case of MIC90 studies. Cytotoxic effects on planktonic and on mature biofilms of Candida species at MEC10 concentrations were further evaluated with fluorescent live/dead discrimination techniques. Candida glabrata, Candida guilliermondii, and Candida parapsilosis were the species most sensitive to Ar and Sc. Ar and Sc were also found to promote the accumulation of intracellular reactive oxygen species (ROS) by increasing oxidative stress at their respective MEC10 concentrations against the tested planktonic Candida species. Ar and Sc possess dose-dependent antifungal action but the underlying mechanism type (fungistatic and fungicidal) is not clear yet. Our data suggest that Ar and Sc found in herbal plants might have potential usage in the fight against Candida biofilms.

Download Full-text

Nonlinear Osmotic Properties of the Cell Nucleus

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206197 ◽

2009 ◽

Author(s):

John D. Finan ◽

Kevin J. Chalut ◽

Adam Wax ◽

Farshid Guilak

Keyword(s):

Articular Cartilage ◽

Cell Membrane ◽

Osmotic Stress ◽

Biological Function ◽

Articular Chondrocytes ◽

Underlying Mechanism ◽

Osmotic Sensitivity ◽

Fixed Charges ◽

Dissolved Ions ◽

Osmotic Properties

Osmotic stress affects biological function in articular chondrocytes and plays an important role in mechanotransduction in articular cartilage. One potential pathway for osmotic sensitivity in chondrocytes is direct deformation of the nucleus by osmotic stress [1,2]. However, the mechanism of this phenomenon is currently unclear. The nucleus is not contained within a semi-permeable lipid bilayer as are most osmotically sensitive organelles. It is conceivable that fixed charges in chromatin might attract dissolved ions and render it osmotically sensitive. However, this model cannot account for the abolition of the osmotic sensitivity of the nucleus by permeabilization of the cell membrane [3]. The goal of this study was to characterize the osmotic sensitivity of the chondrocyte nucleus and determine the underlying mechanism.

Download Full-text

TRAIL promotes epithelial-to-mesenchymal transition by inducing PD-L1 expression in esophageal squamous cell carcinomas

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01972-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Huanyu Zhang ◽

Guohui Qin ◽

Chaoqi Zhang ◽

Huiyun Yang ◽

Jinyan Liu ◽

...

Keyword(s):

Western Blot ◽

Squamous Cell ◽

Mechanism Of Action ◽

Epithelial To Mesenchymal Transition ◽

Biological Function ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Mesenchymal Transition

Abstract Background Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated. Methods The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and epithelial-mesenchymal transition (EMT)- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The xenograft mouse experiments and lung metastasis model were performed to confirm our findings in vitro. Results Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced EMT and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo. Conclusions These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.

Download Full-text

Responsiveness of cats (Felidae) to silver vine (Actinidia polygama), Tatarian honeysuckle (Lonicera tatarica), valerian (Valeriana officinalis) and catnip (Nepeta cataria)

BMC Veterinary Research ◽

10.1186/s12917-017-0987-6 ◽

2017 ◽

Vol 13 (1) ◽

Cited By ~ 13

Author(s):

Sebastiaan Bol ◽

Jana Caspers ◽

Lauren Buckingham ◽

Gail Denise Anderson-Shelton ◽

Carrie Ridgway ◽

...

Keyword(s):

Valeriana Officinalis ◽

Nepeta Cataria ◽

Actinidia Polygama

Download Full-text

Circ-SMO-encoded 193 a.a. Confers Chemotherapy Resistance and Immune Escape to Glioma Stem Cells

10.21203/rs.3.rs-583477/v1 ◽

2021 ◽

Author(s):

sheng yan ◽

shengyong wang ◽

xixi li ◽

yibing yang ◽

xujia wu ◽

...

Keyword(s):

Stem Cells ◽

Cell Death ◽

Western Blotting ◽

Biological Function ◽

Immune Escape ◽

Chemotherapy Resistance ◽

Underlying Mechanism ◽

Glioma Stem Cells ◽

Qrt Pcr ◽

Apoptosis Assay

Abstract Background: Emerging evidence indicates that circRNAs and their encoded proteins contribute to the tumorigenesis of glioma; however, the biological function and underlying mechanism of chemotherapy resistance and immune escape are largely known.Methods: We applied qRT-PCR, western blotting and immunohistochemistry to detect the expression level and correlation between Bax and PDL1. We next applied an apoptosis assay to detect chemotherapy resistance and immune escape.Results: Circ-SMO and 193 a.a. were upregulated in temozolomide-resistant tumours and tumour-associated immune escape tumours. Circ-SMO and 193 a.a. inhibited temozolomide-induced cell death and promoted PDL1 expression.Conclusion: Circ-SMO and 193 a.a. promote chemotherapy resistance and immune escape by modulating autophagy and PDL1 expression.

Download Full-text

Biological Function of Calcium-Sensing Receptor (CAS) and Its Coupling Calcium Signaling in Plants

10.20944/preprints201812.0028.v1 ◽

2018 ◽

Author(s):

Yubin Zhang ◽

Qing Li ◽

Yijie Wang ◽

Lili Sun ◽

Wuliang shi

Keyword(s):

Calcium Signaling ◽

Biological Function ◽

Underlying Mechanism ◽

Multiple Roles ◽

Stomatal Movement ◽

Calcium Sensing Receptor ◽

Biotic Stresses ◽

Calcium Sensing ◽

Phosphorylation Mechanism

The calcium-sensing receptor (CAS), as a chloroplast thylakoid membrane protein, involved in the process of [Ca2+] ext-induced [Ca2+]cyt increase (CICI) in the plant. However, the underlying mechanism regulating this process is lacking. Furthermore, recent evidence suggests that CAS may perform additional roles in the plant. Here, we provide an update covering the multiple roles of CAS in stomatal movement regulation and calcium signaling in the plant. We also analysis the possible phosphorylation mechanism of CAS by light and discuss the role of CAS in abiotic stress (drought, salt stress) and biotic stresses (plant immune signaling). Finally, we provide a perspective for future experiments which are required to fill gaps in our understanding of the biological function of CAS in the plant.

Download Full-text

TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

10.21203/rs.3.rs-117700/v1 ◽

2020 ◽

Author(s):

Huanyu Zhang ◽

Guohui Qin ◽

Huiyun Yang ◽

Jinyan Liu ◽

Peng Wu ◽

...

Keyword(s):

Western Blot ◽

Squamous Cell ◽

Mechanism Of Action ◽

Epithelial To Mesenchymal Transition ◽

Biological Function ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Mesenchymal Transition

Abstract Background: Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated.Methods: The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and EMT- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The PDX Model were performed to confirm our findings in vitro.Results: Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced epithelial-mesenchymal transition (EMT) and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo.Conclusions: These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.Financial support: This work was supported by the National Key Research and Development (2018YFC1313400), the National Nature Science Foundation of China (U1804281, 91942314) and the National Science Fund for Distinguished Young Scholars (82001659).

Download Full-text

STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1450-2 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 6

Author(s):

Linling Lin ◽

Jian Xiao ◽

Liang Shi ◽

Wangwang Chen ◽

Yugang Ge ◽

...

Keyword(s):

Bioinformatics Analysis ◽

Biological Function ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Quantitative Real Time Pcr ◽

Reporter Assays ◽

Proliferation And Metastasis

Abstract Background Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC. Methods The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments. Results STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/β-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6. Conclusions STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/β-catenin signalling in GC.

Download Full-text

Structural insight into the length-dependent binding of ssDNA by SP_0782 from Streptococcus pneumoniae, reveals a divergence in the DNA-binding interface of PC4-like proteins

Nucleic Acids Research ◽

10.1093/nar/gkz1045 ◽

2019 ◽

Author(s):

Shuangli Li ◽

Guoliang Lu ◽

Xiang Fang ◽

Theresa A Ramelot ◽

Michael A Kennedy ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Dna Binding ◽

Genome Stability ◽

Biological Function ◽

Underlying Mechanism ◽

Binding Property ◽

Ssdna Binding ◽

Binding Interface ◽

Nmr Study ◽

Insight Into

Abstract SP_0782 from Streptococcus pneumoniae is a dimeric protein that potentially binds with single-stranded DNA (ssDNA) in a manner similar to human PC4, the prototype of PC4-like proteins, which plays roles in transcription and maintenance of genome stability. In a previous NMR study, SP_0782 exhibited an ssDNA-binding property different from YdbC, a prokaryotic PC4-like protein from Lactococcus lactis, but the underlying mechanism remains unclear. Here, we show that although SP_0782 adopts an overall fold similar to those of PC4 and YdbC, the ssDNA length occupied by SP_0782 is shorter than those occupied by PC4 and YdbC. SP_0782 exhibits varied binding patterns for different lengths of ssDNA, and tends to form large complexes with ssDNA in a potential high-density binding manner. The structures of SP_0782 complexed with different ssDNAs reveal that the varied binding patterns are associated with distinct capture of nucleotides in two major DNA-binding regions of SP_0782. Moreover, a comparison of known structures of PC4-like proteins complexed with ssDNA reveals a divergence in the binding interface between prokaryotic and eukaryotic PC4-like proteins. This study provides insights into the ssDNA-binding mechanism of PC4-like proteins, and benefits further study regarding the biological function of SP_0782, probably in DNA protection and natural transformation.

Download Full-text