2,578 results
Search Results
102. Linalool Impress Colorectal Cancer Deterioration by Mediating AKT/mTOR and JAK2/STAT3 Signaling Pathways.
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Hou, Min, Zhang, Yakun, Huang, Qingmei, Zhan, Hongmei, Jia, Tingting, Li, Min, Hu, Jing, and Zhao, Yanli
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DISEASE progression ,PROTEIN kinases ,STAT proteins ,TERPENES ,ANTINEOPLASTIC agents ,APOPTOSIS ,COLORECTAL cancer ,JANUS kinases ,CELLULAR signal transduction ,CELL survival ,CELL motility ,CELL lines - Abstract
Colorectal cancer (CRC) is one of the more common causes of cancer death worldwide. Chemotherapy is effective in the treatment of CRC, but it can produce a range of adverse effects that can significantly reduce the quality of life of CRC patients. The selection of drugs that are effective in treating CRC with few adverse effects is now an important task and is aimed at prolonging the survival of patients and improving their prognosis. In this study, CRC cells were treated with linalool using CRC cell lines as the study subjects, and cell viability, apoptosis, and cell migration were observed after treatment. Previous studies have demonstrated the therapeutic effects of linalool on CRC and its ability to inhibit CRC progression by modulating the AKT/mTOR and JAK2/STAT3 pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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103. TPM4 promotes cell migration by modulating F-actin formation in lung cancer.
- Author
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Zhao, Xiaoting, Jiang, Mei, and Wang, Ziyu
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CELL migration ,LUNG cancer ,MICROFILAMENT proteins ,CELL motility ,F-actin - Abstract
Background: Tropomyosin 4 (TPM4) is a member of the tropomyosin family of actin-binding proteins. Abnormal level of TPM4 is found in several cancers, and TPM4 is considered as a potential detecting marker for ovarian cancer, breast cancer, colon cancer, keratoacanthoma and esophageal squamous cell carcinoma. In this paper, the function of TPM4 in lung cancer cell lines was determined. Materials and methods: TPM4 knockout cells were constructed by CRISPR/CAS9 technique. TPM4 overexpression cells were also constructed based on TPM4 knockout cells. Cell growth ability was detected by MTS assay. The potency of cell motility was investigated using transwell assay and wound scratch assay. The protein levels in lung cancer cells were determined by western-blot. Immunofluorescence technique was used to image the structure of F-actin. Results: As a result, TPM4 downregulation and TPM4 upregulation cell models were obtained successfully. Cell motility was inhibited by the suppression of TPM4 while cell migration was enhanced in TPM4 upregulated cells. But TPM4 was not involved in cell proliferation and EMT progression. Microfilaments were depolymerized result from the suppression of TPM4 expression. And F-actin assembly was increased when TPM4 was upregulated. Conclusion: In summary, TPM4 was able to promote cell motility by altering the actin cytoskeleton directly. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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104. The relationship between semen seminal plasma ions and sperm cell velocities of wild-caught longspine scraper, Capoeta trutta.
- Author
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Özgür, Mustafa Erkan, Maraş, Zeynep, and Erdoğan, Selim
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TRACE metals ,SPERMATOZOA ,SEMEN ,SEMEN analysis ,CELL motility ,ION mobility ,VELOCITY ,SPERM motility - Abstract
In this study, semen seminal plasma contents and the motility of sperm cells were determined in Capoeta trutta via a computer-assisted sperm analysis system. In addition, we evaluated the relationship between semen seminal plasma ions and the velocities of sperm cells. Although the predominant ions were K (206.84±20.61 mg L -1) and Na (128.06±23.82 mg L -1) in the semen seminal plasma, Ca (14.05±4.13 mg L -1) and Mg (3.35±0.44 mg L -1) were not predominate according to our results. However, partially strong relationships between the curvilinear velocity value (VCL) and K (R2=0.67 ; p<0.05) were found, while it was moderate with Mg (R2=0.48 ; p<0.05). There was a weak relationship with Na (R2=0.17 ; p<0.05) and Ca (R2=0.34 ; p<0.05). In our results, while the trace metals were determined as Zn > Al > B > Li > Cu in semen seminal plasma, they are not correlated with sperm cell velocities. Finally, we hope that the present information on the motility parameters of Capoeta trutta in this paper will eventually help artificial insemination in reproduction practices. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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105. Osmotic stress activates nif and fix genes and induces the Rhizobium tropici CIAT 899 Nod factor production via NodD2 by up-regulation of the nodA2 operon and the nodA3 gene.
- Author
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del Cerro, Pablo, Megías, Manuel, López-Baena, Francisco Javier, Gil-Serrano, Antonio, Pérez-Montaño, Francisco, and Ollero, Francisco Javier
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FACTORS of production ,OSMOTIC pressure ,NITROGEN fixation ,BACTERIAL proteins ,COMMON bean ,GENES - Abstract
The symbiosis between rhizobia and legumes is characterized by a complex molecular dialogue in which the bacterial NodD protein plays a major role due to its capacity to activate the expression of the nodulation genes in the presence of appropiate flavonoids. These genes are involved in the synthesis of molecules, the nodulation factors (NF), responsible for launching the nodulation process. Rhizobium tropici CIAT 899, a rhizobial strain that nodulates Phaseolus vulgaris, is characterized by its tolerance to multiple environmental stresses such as high temperatures, acidity or elevated osmolarity. This strain produces nodulation factors under saline stress and the same set of CIAT 899 nodulation genes activated by inducing flavonoids are also up-regulated in a process controlled by the NodD2 protein. In this paper, we have studied the effect of osmotic stress (high mannitol concentrations) on the R. tropici CIAT 899 transcriptomic response. In the same manner as with saline stress, the osmotic stress mediated NF production and export was controlled directly by NodD2. In contrast to previous reports, the nodA2FE operon and the nodA3 and nodD1 genes were up-regulated with mannitol, which correlated with an increase in the production of biologically active NF. Interestingly, in these conditions, this regulatory protein controlled not only the expression of nodulation genes but also the expression of other genes involved in protein folding and synthesis, motility, synthesis of polysaccharides and, surprinsingly, nitrogen fixation. Moreover, the non-metabolizable sugar dulcitol was also able to induce the NF production and the activation of nod genes in CIAT 899. [ABSTRACT FROM AUTHOR]
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- 2019
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106. Cancer cells in the tumor core exhibit spatially coordinated migration patterns.
- Author
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Staneva, Ralitza, El Marjou, Fatima, Barbazan, Jorge, Krndija, Denis, Richon, Sophie, Clark, Andrew G., and Vignjevic, Danijela Matic
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CELL tumors ,CANCER cells ,CYTOSKELETON ,CELL motility ,CANCER cell migration - Abstract
In the early stages of metastasis, cancer cells exit the primary tumor and enter the vasculature. Although most studies have focused on the tumor invasive front, cancer cells from the tumor core can also potentially metastasize. To address cell motility in the tumor core,we imaged tumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local 'currents' and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides newinsight into the dynamics of cancercells inthe tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis. This article has an associated FirstPerson interviewwith the first author of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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107. NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma
- Author
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Marian Novak, Nathan Harris, Stuart G. Jarrett, Glenn Merlino, Andrezj Slominski, and David M. Kaetzel
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Male ,Hypoxanthine Phosphoribosyltransferase ,Pathology ,Cancer Research ,Skin Neoplasms ,DNA Repair ,Cell motility ,Metastasis ,Mice ,0302 clinical medicine ,Cell Movement ,Tumor Cells, Cultured ,Transgenic mice ,Melanoma ,Hepatocyte growth factor ,0303 health sciences ,Cell migration ,General Medicine ,NM23 Nucleoside Diphosphate Kinases ,3. Good health ,Oncology ,Metastasis suppressor ,030220 oncology & carcinogenesis ,Female ,Research Paper ,NM23 ,medicine.drug ,Ultraviolet radiation ,Genetically modified mouse ,medicine.medical_specialty ,Ultraviolet Rays ,Mice, Transgenic ,Biology ,Genomic Instability ,03 medical and health sciences ,In vivo ,medicine ,Animals ,Humans ,030304 developmental biology ,Wound Healing ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Mutagenesis ,Mutation ,Cancer research ,Skin cancer ,DNA Damage - Abstract
Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of
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108. A PUS based nets weighting mechanism for power, hold, and setup timing optimization.
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Chentouf, Mohamed and El Abidine Alaoui Ismaili, Zine
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SETUP time , *SUPPURATION , *CELL motility , *APPLICATION-specific integrated circuits , *INDUSTRIAL design - Abstract
Power consumption has become a major constraint in VLSI design. A considerable power increase is usually seen during the hold closure step of the physical design done in post-CTS and post-route stages. Hold optimization is performed by applying some circuit-level changes such as buffer insertion, cell sizing, useful-skew or cell movement. Moving the hold fixing problem to the pre-CTS stage represents a big opportunity for power saving and design closure improvement. In this paper, we present a novel power, hold, and setup driven placement algorithm. The objective is to reduce not only the setup, but also the hold violations while keeping the power consumption under control. This objective is achieved by changing the weighting mechanism of a commercial Power and Timing Driven Placement (PTDP) engine to include power, hold and electrical Design Rule Constraints (eDRC) in the weighting equation which will drive the placer to place the cells that are in the setup critical paths or connected with high power nets close to each other and relax the weight of the cells that are on hold critical paths, so the placer may place them far from each other. As a consequence, critical setup, power or eDRC nets will be shortened to reduce the delay, and critical hold nets will be elongated to add delay and hence improve the placement overall Quality of Results (QoR). This approach was deployed on 40 industrial designs of different customers, sizes, technologies, and complexities and showed very good improvement, not only in timing (setup and hold) and power consumption but also in total area and design routability. The timing gain is about 15% and 13% in TNS and THS respectively. The total power gain is about 9%, distributed as 7% in leakage power and 9% in dynamic power. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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109. Research Progress of Mesenchymal Stem Cells and Their Exosomes on Tumors.
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Shuyue CUI, Shuai TANG, Xiaoling DING, and Gang DING
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TUMOR diagnosis ,EXOSOMES ,CARCINOGENESIS ,IMMUNOMODULATORS ,CELL motility ,TUMORS ,CELL lines ,MEDICAL research ,MESENCHYMAL stem cells - Abstract
In China, malignant tumor is the main cause of death in both urban and rural areas. Mesenchymal stem cells (MSCs) have multidirectional differentiation potential, self-renewal ability and good immunomodulatory properties. Exosomes, as important paracrine substances of MSCs, mediate information exchange and transmission between cells in tumor microenvironment and influence the occurrence and development of tumors. Recently, conflicting findings have been reported on the effects of MSCs and their exosomes on tumors. On the one hand, MSCs and their exosomes are tumorigenic and can target specific sites to inhibit tumor growth; On the other hand, there is also evidence that MSCs could affect tumor growth and migration as part of the tumor microenvironment. In this paper, we will review the relationship between MSCs and exosomes and tumorgenesis and development, as well as how MSCs and exosomes play different roles in tumorgenesis and development, in order to provide beneficial help for tumor diagnosis, prognosis and precise treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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110. Using deep reinforcement learning to speed up collective cell migration.
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Hou, Hanxu, Gan, Tian, Yang, Yaodong, Zhu, Xianglei, Liu, Sen, Guo, Weiming, and Hao, Jianye
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REINFORCEMENT learning ,DEEP learning ,CELL motility ,MACHINE learning ,BIOMIMETIC materials - Abstract
Background: Collective cell migration is a significant and complex phenomenon that affects many basic biological processes. The coordination between leader cell and follower cell affects the rate of collective cell migration. However, there are still very few papers on the impacts of the stimulus signal released by the leader on the follower. Tracking cell movement using 3D time-lapse microscopy images provides an unprecedented opportunity to systematically study and analyze collective cell migration. Results: Recently, deep reinforcement learning algorithms have become very popular. In our paper, we also use this method to train the number of cells and control signals. By experimenting with single-follower cell and multi-follower cells, it is concluded that the number of stimulation signals is proportional to the rate of collective movement of the cells. Such research provides a more diverse approach and approach to studying biological problems. Conclusion: Traditional research methods are always based on real-life scenarios, but as the number of cells grows exponentially, the research process is too time consuming. Agent-based modeling is a robust framework that approximates cells to isotropic, elastic, and sticky objects. In this paper, an agent-based modeling framework is used to establish a simulation platform for simulating collective cell migration. The goal of the platform is to build a biomimetic environment to demonstrate the importance of stimuli between the leading and following cells. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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111. Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature.
- Author
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Roy, Molly, Yang, Yu-Ping, Bosquet, Olivia, Deo, Sapna K., and Daunert, Sylvia
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EXOSOMES ,GENETICS ,OVARIAN tumors ,METASTASIS ,MICRORNA ,CELL motility ,ENDOMETRIAL tumors ,FEMALE reproductive organ tumors - Abstract
Simple Summary: Gynecologic malignancies are those that affect the female reproductive organs, including the ovary, uterus, and cervix. Gynecologic malignancies as a group vary significantly in initial clinical presentation, degree and pattern of spread, and treatment modalities. Our knowledge of the role exosomes play in cancer growth and spread is expanding rapidly. The promise these nanovesicles hold in cancer diagnostics and therapeutics is undeniable, and may be the key to improving the diagnosis and treatment of gynecologic cancers. This paper serves to review laboratory techniques utilized in isolating and studying exosomes, the current state of understanding of exosomes in gynecologic malignancies, and the potential for clinical applications that exosomes may hold. Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies. [ABSTRACT FROM AUTHOR]
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- 2022
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112. The role of intracellular signaling in the stripe formation in engineered Escherichia coli populations.
- Author
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Xue, Xiaoru, Xue, Chuan, and Tang, Min
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ESCHERICHIA coli enzymes ,ESCHERICHIA coli proteins ,ESCHERICHIA coli physiology ,COMPUTATIONAL biology ,CELL division - Abstract
Recent experiments showed that engineered Escherichia coli colonies grow and self-organize into periodic stripes with high and low cell densities in semi-solid agar. The stripes develop sequentially behind a radially propagating colony front, similar to the formation of many other periodic patterns in nature. These bacteria were created by genetically coupling the intracellular chemotaxis pathway of wild-type cells with a quorum sensing module through the protein CheZ. In this paper, we develop multiscale models to investigate how this intracellular pathway affects stripe formation. We first develop a detailed hybrid model that treats each cell as an individual particle and incorporates intracellular signaling via an internal ODE system. To overcome the computational cost of the hybrid model caused by the large number of cells involved, we next derive a mean-field PDE model from the hybrid model using asymptotic analysis. We show that this analysis is justified by the tight agreement between the PDE model and the hybrid model in 1D simulations. Numerical simulations of the PDE model in 2D with radial symmetry agree with experimental data semi-quantitatively. Finally, we use the PDE model to make a number of testable predictions on how the stripe patterns depend on cell-level parameters, including cell speed, cell doubling time and the turnover rate of intracellular CheZ. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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113. Structural organization and energy storage in crosslinked actin assemblies.
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Ma, Rui and Berro, Julien
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ACTIN ,CLATHRIN ,ENDOCYTOSIS ,FIBERS ,FIMBRIN ,POLYMERIZATION - Abstract
During clathrin-mediated endocytosis in yeast cells, short actin filaments (< 200nm) and crosslinking protein fimbrin assemble to drive the internalization of the plasma membrane. However, the organization of the actin meshwork during endocytosis remains largely unknown. In addition, only a small fraction of the force necessary to elongate and pinch off vesicles can be accounted for by actin polymerization alone. In this paper, we used mathematical modeling to study the self-organization of rigid actin filaments in the presence of elastic crosslinkers in conditions relevant to endocytosis. We found that actin filaments condense into either a disordered meshwork or an ordered bundle depending on filament length and the mechanical and kinetic properties of the crosslinkers. Our simulations also demonstrated that these nanometer-scale actin structures can store a large amount of elastic energy within the crosslinkers (up to 10k
B T per crosslinker). This conversion of binding energy into elastic energy is the consequence of geometric constraints created by the helical pitch of the actin filaments, which results in frustrated configurations of crosslinkers attached to filaments. We propose that this stored elastic energy can be used at a later time in the endocytic process. As a proof of principle, we presented a simple mechanism for sustained torque production by ordered detachment of crosslinkers from a pair of parallel filaments. [ABSTRACT FROM AUTHOR]- Published
- 2018
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114. Study on invasion and migration of malignant glioma.
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YANG Xue-jun, HAI Long, and YU Sheng-ping
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BRAIN anatomy ,BIOLOGY ,CANCER invasiveness ,CELL motility ,CENTRAL nervous system ,COMBINED modality therapy ,DRUG resistance ,GLIOMAS ,NEUROSURGERY ,NEUROLOGY ,RADIATION ,DISEASE relapse ,DISEASE progression - Abstract
Glioma shows diffuse infiltrative growth in the brain parenchyma. Even following the principle of "maximum safe resection", the residual tumor cells are resistant to adjuvant chemoradiotherapy and continue to invase and migrate in the brain tissue. This is the main reason for the recurrence of glioma and the dissemination in the central nervous system (CNS). As a result, understanding the mode of glioma invasion and migration can provide a new method for the treatment of glioma. This paper reviews our research findings of the invasion and migration of glioma during the period of Twelfth Five-Year Plan for National Economic and Social Development. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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115. Transitions in development -- an interview with Margot Kossmann Williams.
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Eve, Alex
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DEVELOPMENTAL biology ,EPITHELIAL-mesenchymal transition ,CELL motility - Published
- 2022
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116. Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study.
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Paganelli, Alessia, Zaffonato, Marco, Donati, Benedetta, Torricelli, Federica, Manicardi, Veronica, Lai, Michela, Spadafora, Marco, Piana, Simonetta, Ciarrocchi, Alessia, and Longo, Caterina
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SQUAMOUS cell carcinoma ,RISK assessment ,SKIN tumors ,CELL proliferation ,CANCER patients ,CELL motility ,DESCRIPTIVE statistics ,METASTASIS ,GENE expression ,GENE expression profiling ,CASE-control method ,INDIVIDUALIZED medicine ,MOLECULAR pathology - Abstract
Simple Summary: This study investigates the characteristics of metastatic cutaneous squamous cell carcinoma (cSCC) to improve patient risk stratification. By comparing patients with metastatic and non-metastatic cSCC, we analyzed cSCC skin samples for histological parameters and gene expression profiles. Out of 770 genes tested, 67 were differentially expressed in metastatic cSCC. These were mainly related to immune regulation, skin integrity, angiogenesis, cell migration, and proliferation. The findings suggest that combining histological and molecular profiles can help identify features specific to metastatic cSCC, potentially enhancing patient risk assessment. Background: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC. Methods: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes. Results: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation. Conclusion: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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117. P18: Novel Anticancer Peptide from Induced Tumor-Suppressing Cells Targeting Breast Cancer and Bone Metastasis.
- Author
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Cui, Changpeng, Huo, Qingji, Xiong, Xue, Na, Sungsoo, Mitsuda, Masaru, Minami, Kazumasa, Li, Baiyan, and Yokota, Hiroki
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COMPUTER-assisted molecular modeling ,FLUORESCENCE polarization immunoassay ,RESEARCH funding ,BREAST tumors ,ANTINEOPLASTIC agents ,TRYPSIN ,ANTIMICROBIAL peptides ,TREATMENT effectiveness ,CANCER cell culture ,DESCRIPTIVE statistics ,CELL motility ,BONE metastasis ,MICE ,CELL lines ,ANIMAL experimentation ,WESTERN immunoblotting ,ONE-way analysis of variance ,CELL survival ,PHARMACODYNAMICS - Abstract
Simple Summary: This study focused on finding effective anticancer peptides (ACPs) from induced tumor-suppressing cells (iTSCs) to combat breast cancer metastasis to the skeletal system. This study identified P18 as the most potent ACP from a pool of candidates, derived from a protein called Arhgdia. P18 showed significant inhibitory effects on breast cancer cell viability, migration, and invasion, as well as interfering with certain cancer-promoting proteins and GTPase signaling. Importantly, P18 demonstrated enhanced effectiveness when combined with traditional chemotherapy drugs, without significantly affecting healthy cells. Moreover, it mitigated the bone loss associated with breast cancer spread to bones. This study suggests that P18, especially in its modified form (Ac-P18-NH2), could be a promising candidate for breast cancer treatment and preventing bone destruction by regulating specific cellular signaling pathways. Background: The skeletal system is a common site for metastasis from breast cancer. In our prior work, we developed induced tumor-suppressing cells (iTSCs) capable of secreting a set of tumor-suppressing proteins. In this study, we examined the possibility of identifying anticancer peptides (ACPs) from trypsin-digested protein fragments derived from iTSC proteomes. Methods: The efficacy of ACPs was examined using an MTT-based cell viability assay, a Scratch-based motility assay, an EdU-based proliferation assay, and a transwell invasion assay. To evaluate the mechanism of inhibitory action, a fluorescence resonance energy transfer (FRET)-based GTPase activity assay and a molecular docking analysis were conducted. The efficacy of ACPs was also tested using an ex vivo cancer tissue assay and a bone microenvironment assay. Results: Among the 12 ACP candidates, P18 (TDYMVGSYGPR) demonstrated the most effective anticancer activity. P18 was derived from Arhgdia, a Rho GDP dissociation inhibitor alpha, and exhibited inhibitory effects on the viability, migration, and invasion of breast cancer cells. It also hindered the GTPase activity of RhoA and Cdc42 and downregulated the expression of oncoproteins such as Snail and Src. The inhibitory impact of P18 was additive when it was combined with chemotherapeutic drugs such as Cisplatin and Taxol in both breast cancer cells and patient-derived tissues. P18 had no inhibitory effect on mesenchymal stem cells but suppressed the maturation of RANKL-stimulated osteoclasts and mitigated the bone loss associated with breast cancer. Furthermore, the P18 analog modified by N-terminal acetylation and C-terminal amidation (Ac-P18-NH2) exhibited stronger tumor-suppressor effects. Conclusions: This study introduced a unique methodology for selecting an effective ACP from the iTSC secretome. P18 holds promise for the treatment of breast cancer and the prevention of bone destruction by regulating GTPase signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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118. Myosin II mediates Shh signals to shape dental epithelia via control of cell adhesion and movement.
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Du, Wei, Verma, Adya, Ye, Qianlin, Du, Wen, Lin, Sandy, Yamanaka, Atsushi, Klein, Ophir D., and Hu, Jimmy K.
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CELL adhesion ,CELL motility ,MYOSIN ,MOLECULAR motor proteins ,EPITHELIUM ,EMBRYOLOGY ,HAIR follicles ,AMELOBLASTS - Abstract
The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination. Author summary: During embryonic development, teeth, hair follicles, and glands are examples of ectodermally-derived organs that are formed from slightly thickened epithelial layers, called placodes. These placodes undergo remarkable morphological transformations to first invaginate as an epithelial bud and later morph into a more complex structure resembling the adult organ. Movement and rearrangement of epithelial cells are thought to drive tooth invagination. But there remain key knowledge gaps in our understanding of the underlying molecular mechanisms and signaling regulation that control cell movement and epithelial morphogenesis. Here, we use the developing mouse tooth as a model to show that Shh, a signaling molecule from the early tooth signaling center, plays an important role in activating the motor protein non-muscle myosin II in dental epithelial cells. Myosin II is in turn required to promote strong adhesion between cells and power dental epithelial cells to converge towards the midline of the tooth bud to drive tooth invagination. Our results thus define the in vivo function of myosin II during epithelial invagination and explain how signaling from secreted molecules can facilitate morphogenetic cell movements via myosin II. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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119. Citral in lemon myrtle, lemongrass, litsea, and melissa essential oils suppress the growth and invasion of breast cancer cells.
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Nagata, Takuya, Satou, Tadaaki, Hayashi, Shinichiro, Satyal, Prabodh, Watanabe, Manabu, Riggs, Brannick, and Saida, Yoshihisa
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THERAPEUTIC use of antineoplastic agents ,DATA analysis ,RESEARCH funding ,ESSENTIAL oils ,BREAST tumors ,CELL proliferation ,CHALONES ,APOPTOSIS ,IMMUNODIAGNOSIS ,CELL motility ,PLANT extracts ,CELL lines ,CELL culture ,GAS chromatography ,ONE-way analysis of variance ,STATISTICS ,LEMONGRASS ,BIOLOGICAL assay ,DATA analysis software ,COMPARATIVE studies ,LEMON balm ,CELL surface antigens - Abstract
Objective: Although cancer therapy suppresses recurrence and prolongs life, it may be accompanied by strong side effects; thus, there is a strong demand for the development effective treatments with fewer side effects. Cancer therapy using plant-derived essential oils is attracting attention as one promising method. This study investigated the antitumor effects of essential oil volatiles on breast cancer cells and identifies four essential oils that display antitumor activity. Methods: Breast cancer cells were cultured in a 96-well plate, then one of twenty essential oils was added dropwise to the central well. The plate was incubated at 37 °C for 48 h and the effect of the volatile components of each essential oil on the surrounding breast cancer cell growth ability was examined using an MTT assay. Gas chromatography was used to investigate the concentration of the transpiration components that may affect cancer cells. Results: Of the 20 essential oils, Lemongrass, Lemon myrtle, Litsea, and Melissa displayed strong anti-tumor effects. These essential oils inhibited the growth of nearby breast cancer cells, even when diluted more than 500-fold. The transpiration component of lemon Myrtle showed the strongest antitumor effect, but was the least cytotoxic to mononuclear cells in normal peripheral blood (PBMC). Each of these essential oils contained a very large amount of citral. The IC
50 against breast cancer cells when citral was volatilized from each essential oil was 1.67 µL/mL for geranial and 1.31 µL/mL for neral. Volatilized citral alone showed strong anti-proliferation and infiltration-inhibiting effects. Conclusion: The transpiration components of Lemongrass, Lemon myrtle, Litsea, and Melissa are thought to inhibit breast cancer cell proliferation due to their high levels of citral. [ABSTRACT FROM AUTHOR]- Published
- 2024
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120. Psychometric Properties of the Knowledge of Hydration among Foreign Students of Óbuda University, Hungary.
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Ogbolu, Melvin Omone, Eniade, Olanrewaju D., Vincze, Miklós, and Kozlovszky, Miklós
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HEALTH literacy ,DRINKING (Physiology) ,CROSS-sectional method ,PEARSON correlation (Statistics) ,MENTAL health ,CRONBACH'S alpha ,RESEARCH funding ,RESEARCH methodology evaluation ,RESEARCH evaluation ,CELL motility ,CHI-squared test ,DESCRIPTIVE statistics ,HYDRATION ,EXPERIMENTAL design ,PSYCHOMETRICS ,RESEARCH methodology ,INTRACLASS correlation ,BODY fluids ,FACTOR analysis ,DATA analysis software ,DEHYDRATION ,RELIABILITY (Personality trait) - Abstract
It is known that the quantity, makeup, and distribution of bodily fluids have a significant impact on the cognitive health, physiological health, and cell activity of human beings. This narrative could be influenced by the level of knowledge about hydration, dehydration, and the practice of Adequate Water Intake (AWI) of an individual based on the recommended daily Total Water Intake (TWI) by either the World Health Organization (WHO) or the European Food Safety Authority (EFSA). In this study, we have developed and validated a scale to adequately measure knowledge of the recommended daily Total Water Intake (TWI) practices among foreign students at Óbuda University, Hungary. Hence, we implemented an 11-item scale to measure the Knowledge of Hydration (KH-11) and evaluate its psychometric properties among students. This study is an online cross-sectional study assessing water intake knowledge with the use of the KH-11 tool among 323 students with ages ranging from 18 to 35 years, who have enrolled for at least two semesters at the University. The statistical analysis performed was reliability (using Cronbach alpha ≥ 70%) and factor analysis. Knowledge levels were categorized as poor (<50%), intermediate (50–70%), or adequate (71–100%). The intraclass correlation, chi-square, and rotated component matrix were also estimated and reported. Data were analyzed using SPSS version 25. Cronbach's alpha analysis revealed that the KH-11 had an overall good reliability with a value of 0.80, where the survey items had an acceptable level of consistency ranging from 0.75 to 0.81 and demonstrated sufficient independence from each other as Pearson's R within factors was positive and ranged from 0.02 to 0.74. In evaluating the participants' knowledge of hydration, the total possible score for the scale is 72, while the mean score for the KH-11 was 55.2 ± 11.61 SD, and the factor analysis model yielded an acceptable fit (χ
2 = 3259.4, p = 0.000). We recorded a high-level positive concordance of 0.770 with an average intraclass correlation of 0.80 at a 95% CI, where p-value = 0.000. Our findings show that the majority (66.3%) of the students have a good knowledge of hydration. However, the skewed distribution of the knowledge scores suggests that some may have lower levels of knowledge, which may warrant further study to improve knowledge in those students. [ABSTRACT FROM AUTHOR]- Published
- 2024
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121. The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells.
- Author
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Watanabe, Megumi, Sato, Tatsuya, Umetsu, Araya, Ogawa, Toshifumi, Nishikiori, Nami, Suzuki, Megumi, Furuhashi, Masato, and Ohguro, Hiroshi
- Subjects
RNA sequencing ,CELL anatomy ,GLYCOLYSIS ,CELL motility ,GENE expression ,G proteins - Abstract
To investigate the biological significance of Rho-associated coiled-coil-containing protein kinase (ROCK) 2 in the human trabecular meshwork (HTM), changes in both metabolic phenotype and gene expression patterns against a specific ROCK2 inhibitor KD025 were assessed in planar-cultured HTM cells. A seahorse real-time ATP rate assay revealed that administration of KD025 significantly suppressed glycolytic ATP production rate and increased mitochondrial ATP production rate in HTM cells. RNA sequencing analysis revealed that 380 down-regulated and 602 up-regulated differentially expressed genes (DEGs) were identified in HTM cells treated with KD025 compared with those that were untreated. Gene ontology analysis revealed that DEGs were more frequently related to the plasma membrane, extracellular components and integral cellular components among cellular components, and related to signaling receptor binding and activity and protein heterodimerization activity among molecular functions. Ingenuity Pathway Analysis (IPA) revealed that the detected DEGs were associated with basic cellular biological and physiological properties, including cellular movement, development, growth, proliferation, signaling and interaction, all of which are associated with cellular metabolism. Furthermore, the upstream regulator analysis and causal network analysis estimated IL-6, STAT3, CSTA and S1PR3 as possible regulators. Current findings herein indicate that ROCK2 mediates the IL-6/STAT3-, CSTA- and S1PR3-linked signaling related to basic biological activities such as glycolysis in HTM cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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122. Vimentin is a key regulator of cell mechanosensing through opposite actions on actomyosin and microtubule networks.
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Alisafaei, Farid, Mandal, Kalpana, Saldanha, Renita, Swoger, Maxx, Yang, Haiqian, Shi, Xuechen, Guo, Ming, Hehnly, Heidi, Castañeda, Carlos A., Janmey, Paul A., Patteson, Alison E., and Shenoy, Vivek B.
- Subjects
MICROTUBULES ,CYTOPLASMIC filaments ,VIMENTIN ,ACTOMYOSIN ,CELL motility ,EXTRACELLULAR matrix - Abstract
The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin's effects on the transmission of cell contractile forces to the extracellular matrix. Vimentin tunes cell stress by assisting in both actomyosin force transmission and reinforcement of microtubule networks under compression. The competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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123. Role of Hypoxia and Rac1 Inhibition in the Metastatic Cascade.
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Tátrai, Enikő, Ranđelović, Ivan, Surguta, Sára Eszter, and Tóvári, József
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PROTEINS ,IN vitro studies ,DRUG resistance in cancer cells ,CELL proliferation ,CELL motility ,CHEMORADIOTHERAPY ,CELLULAR signal transduction ,METASTASIS ,CELL lines ,HYPOXEMIA ,PHENOTYPES ,DISEASE progression - Abstract
Simple Summary: In recent years, several studies have demonstrated the negative impact of tissue hypoxia on tumor pathology. In a significant number of cases, tumors develop resistance to chemo- and radiotherapy, fostering a more aggressive phenotype of tumor cells. The role of small regulatory proteins in cell motility is well known. In our previous work, we have investigated cell proliferation and motility, as well as expression patterns of factor which induce hypoxia and small regulatory proteins responsible for motility, in tumor cell lines of different tissue origins cultured under hypoxic conditions. In this review, we aim to highlight the significance of inhibiting motility factor mitigating metastasis under hypoxic conditions. We have discussed the effect of hypoxia on metastasis formation and the role of motility factor in this process. Although the molecular link between hypoxia-induced factor and small regulatory protein of motility remains unclear, findings primarily from in vitro studies so far suggests that targeting motility factor and its inhibition could be an effective complementary therapeutic strategy for suppressing tumor metastatic formation. The hypoxic condition has a pivotal role in solid tumors and was shown to correlate with the poor outcome of anticancer treatments. Hypoxia contributes to tumor progression and leads to therapy resistance. Two forms of a hypoxic environment might have relevance in tumor mass formation: chronic and cyclic hypoxia. The main regulators of hypoxia are hypoxia-inducible factors, which regulate the cell survival, proliferation, motility, metabolism, pH, extracellular matrix function, inflammatory cells recruitment and angiogenesis. The metastatic process consists of different steps in which hypoxia-inducible factors can play an important role. Rac1, belonging to small G-proteins, is involved in the metastasis process as one of the key molecules of migration, especially in a hypoxic environment. The effect of hypoxia on the tumor phenotype and the signaling pathways which may interfere with tumor progression are already quite well known. Although the role of Rac1, one of the small G-proteins, in hypoxia remains unclear, predominantly, in vitro studies performed so far confirm that Rac1 inhibition may represent a viable direction for tumor therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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124. Exploring the Enigma: The Role of the Epithelial Protein Lost in Neoplasm in Normal Physiology and Cancer Pathogenesis.
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Lindell, Emma and Zhang, Xiaonan
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CARCINOGENESIS ,PHYSIOLOGY ,CELL motility ,CANCER cell proliferation ,CELL metabolism ,TUMOR growth - Abstract
The cytoskeleton plays a pivotal role in maintaining the epithelial phenotype and is vital to several hallmark processes of cancer. Over the past decades, researchers have identified the epithelial protein lost in neoplasm (EPLIN, also known as LIMA1) as a key regulator of cytoskeletal dynamics, cytoskeletal organization, motility, as well as cell growth and metabolism. Dysregulation of EPLIN is implicated in various aspects of cancer progression, such as tumor growth, invasion, metastasis, and therapeutic resistance. Its altered expression levels or activity can disrupt cytoskeletal dynamics, leading to aberrant cell motility and invasiveness characteristic of malignant cells. Moreover, the involvement of EPLIN in cell growth and metabolism underscores its significance in orchestrating key processes essential for cancer cell survival and proliferation. This review provides a comprehensive exploration of the intricate roles of EPLIN across diverse cellular processes in both normal physiology and cancer pathogenesis. Additionally, this review discusses the possibility of EPLIN as a potential target for anticancer therapy in future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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125. A Novel 2-Methoxyestradiol Derivative: Disrupting Mitosis Inhibiting Cell Motility and Inducing Apoptosis in HeLa Cells In Vitro.
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Njangiru, Isaac Kinyua, Bózsity-Faragó, Noémi, Resch, Vivien Erzsébet, Paragi, Gábor, Frank, Éva, Balogh, György T., Zupkó, István, and Minorics, Renáta
- Subjects
CELL motility ,TUBULINS ,CELL populations ,APOPTOSIS ,HELA cells ,MITOSIS ,CELL proliferation - Abstract
The clinical application of 2-methoxyestradiol (2ME) in cancer therapy has been limited by its low solubility and rapid metabolism. Derivatives of 2ME have been synthesised to enhance bioavailability and decrease hepatic metabolism. Compound 4a, an analog of 2ME, has demonstrated exceptional pharmacological activity, in addition to promising pharmacokinetic profile. Our study, therefore, aimed at exploring the anticancer effects of 4a on the cervical cancer cell line, HeLa. Compound 4a exhibited a significant and dose-dependent antimetastatic and antiinvasive impact on HeLa cells, as determined by wound-healing and Boyden chamber assays, respectively. Hoechst/Propidium iodide (HOPI) double staining showcased a substantial induction of apoptosis via 4a, with minimal necrotic effect. Flow cytometry revealed a significant G2/M phase arrest, accompanied by a noteworthy rise in the sub-G1 cell population, indicating apoptosis, 18 h post-treatment. Moreover, a cell-independent tubulin polymerisation assay illustrated compound 4a's ability to stabilise microtubules by promoting tubulin polymerisation. Molecular modelling experiments depicted that 4a interacts with the colchicine-binding site, nestled between the α and β tubulin dimers. Furthermore, 4a displayed an affinity for binding to and activating ER-α, as demonstrated by the luciferase reporter assay. These findings underscore the potential of 4a in inhibiting HPV18+ cervical cancer proliferation and cellular motility. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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126. The OTX2 Gene Induces Tumor Growth and Triggers Leptomeningeal Metastasis by Regulating the mTORC2 Signaling Pathway in Group 3 Medulloblastomas.
- Author
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Ampudia-Mesias, Elisabet, Cameron, Charles S., Yoo, Eunjae, Kelly, Marcus, Anderson, Sarah M., Manning, Riley, Abrahante Lloréns, Juan E., Moertel, Christopher L., Yim, Hyungshin, Odde, David J., Saydam, Nurten, and Saydam, Okay
- Subjects
CELLULAR signal transduction ,TUMOR growth ,METASTASIS ,GENE expression ,CELL motility ,TUMOR suppressor genes ,HOMEOBOX genes - Abstract
Medulloblastoma (MB) encompasses diverse subgroups, and leptomeningeal disease/metastasis (LMD) plays a substantial role in associated fatalities. Despite extensive exploration of canonical genes in MB, the molecular mechanisms underlying LMD and the involvement of the orthodenticle homeobox 2 (OTX2) gene, a key driver in aggressive MB Group 3, remain insufficiently understood. Recognizing OTX2's pivotal role, we investigated its potential as a catalyst for aggressive cellular behaviors, including migration, invasion, and metastasis. OTX2 overexpression heightened cell growth, motility, and polarization in Group 3 MB cells. Orthotopic implantation of OTX2-overexpressing cells in mice led to reduced median survival, accompanied by the development of spinal cord and brain metastases. Mechanistically, OTX2 acted as a transcriptional activator of the Mechanistic Target of Rapamycin (mTOR) gene's promoter and the mTORC2 signaling pathway, correlating with upregulated downstream genes that orchestrate cell motility and migration. Knockdown of mTOR mRNA mitigated OTX2-mediated enhancements in cell motility and polarization. Analysis of human MB tumor samples (N = 952) revealed a positive correlation between OTX2 and mTOR mRNA expression, emphasizing the clinical significance of OTX2's role in the mTORC2 pathway. Our results reveal that OTX2 governs the mTORC2 signaling pathway, instigating LMD in Group 3 MBs and offering insights into potential therapeutic avenues through mTORC2 inhibition. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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127. A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer.
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Mosca, Nicola, Pezzullo, Mariaceleste, De Leo, Ilenia, Truda, Anna, Marchese, Giovanna, Russo, Aniello, and Potenza, Nicoletta
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ADENOCARCINOMA ,COMPETITIVE endogenous RNA ,RESEARCH funding ,MICRORNA ,CELL proliferation ,CELL motility ,GENE expression ,GLUCOSE transporter 1 deficiency syndrome ,MESSENGER RNA ,LUNG tumors ,ONCOGENES ,BIOLOGICAL assay ,COMPARATIVE studies - Abstract
Simple Summary: Non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are emerging as a driving force for lung cancer, the leading cause of cancer-related death. In this experimental work, we unveiled a novel competing endogenous RNA network (ceRNET) involving the lncRNA JPX, miR-378a-3p, and its downstream oncogenic targets in lung adenocarcinoma cells. First, a reverse expression pattern of JPX and miR-378a-3p was found in tumor tissues compared to normal lungs; subsequently, physical interaction between the molecules was demonstrated. Then, the boosting of either JPX or/and miR-378a-3p levels in lung cancer cells demonstrated the oncogenic role of JPX, the oncosuppressive function of the miRNA, and their functional relationship using an array of biological assays evaluating cell proliferation, migration, invasion, and 3D-spheroid formation. Finally, the ability of JPX to inhibit the silencing activity of miR-378a-3p toward its targets GLUT1, NRP1, YY1, and Wnt5a, and thus the contribution to lung cancer, was demonstrated. Lung cancer is the leading cause of cancer-related death worldwide. Non-coding RNAs are emerging as critical players for the onset and progression of cancer. Analyses of three different datasets revealed that the lncRNA JPX was overexpressed in adenocarcinoma tissues in comparison to normal lungs, as expected for an oncogene. Intriguingly, the predicted binding miR-378a-3p showed a significant inverse correlation with JPX expression. The lncRNA/miRNA physical interaction was validated by reporter vectors. Then, the oncogenic activity of JPX, the tumor-suppressive role of miR-378a-3p, and the contribution of their functional interaction to cancer hallmarks were demonstrated using assays for cell proliferation, migration, invasion, and 3D-spheroid formation. Finally, molecular circuits were investigated by boosting the expression of both JPX and miR-378a-3p, singularly and in combination, demonstrating that JPX counteracted miR-378a-3p silencing activity toward its oncogenic targets GLUT1, NRP1, YY1, and Wnt5a. Overall, the data unveil a novel ceRNET (competing endogenous RNA network), wherein JPX acts as a ceRNA by binding to miR-378a-3p, thus reducing the miRNA silencing activity toward its downstream targets, and eliciting oncogenic pathways driving lung cancer. The knowledge of the network may pave the way to develop new diagnostic panels, and innovative RNA-targeted and RNA-based therapeutic strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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128. PIEZO1 regulates leader cell formation and cellular coordination during collective keratinocyte migration.
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Chen, Jinghao, Holt, Jesse R., Evans, Elizabeth L., Lowengrub, John S., and Pathak, Medha M.
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CELL motility ,KERATINOCYTES ,CELL migration ,ION channels ,WOUND healing ,KERATINOCYTE differentiation - Abstract
The collective migration of keratinocytes during wound healing requires both the generation and transmission of mechanical forces for individual cellular locomotion and the coordination of movement across cells. Leader cells along the wound edge transmit mechanical and biochemical cues to ensuing follower cells, ensuring their coordinated direction of migration across multiple cells. Despite the observed importance of mechanical cues in leader cell formation and in controlling coordinated directionality of cell migration, the underlying biophysical mechanisms remain elusive. The mechanically-activated ion channel PIEZO1 was recently identified to play an inhibitory role during the reepithelialization of wounds. Here, through an integrative experimental and mathematical modeling approach, we elucidate PIEZO1's contributions to collective migration. Time-lapse microscopy reveals that PIEZO1 activity inhibits leader cell formation at the wound edge. To probe the relationship between PIEZO1 activity, leader cell formation and inhibition of reepithelialization, we developed an integrative 2D continuum model of wound closure that links observations at the single cell and collective cell migration scales. Through numerical simulations and subsequent experimental validation, we found that coordinated directionality plays a key role during wound closure and is inhibited by upregulated PIEZO1 activity. We propose that PIEZO1-mediated retraction suppresses leader cell formation which inhibits coordinated directionality between cells during collective migration. Author summary: During the healing of a wound, cells called keratinocytes that make up the outer layer of the skin migrate collectively to close the wound gap. The mechanically activated ion channel PIEZO1 was previously found to inhibit wound closure. Here, through a combined modeling and experimental approach, we investigate the role of PIEZO1 in regulating collective migration. Specialized cells called leader cells, which typically form along the wound edge, are important for guiding the migration of neighboring cells. These leader cells dictate the coordinated directionality, or the cohesiveness of the migration direction between neighboring cells, through the transmission of mechanical and biochemical cues. We find that PIEZO1 activity inhibits the formation of these leader cells and, as a result, inhibits cell coordinated directionality causing the collective movement of cells to become disorganized and less effective in closing the wound. Our findings shed light on the complex mechanisms underlying collective migration, providing valuable insight into how mechanical cues affect the movement of cells during wound closure. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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129. Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome.
- Author
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Di Giuseppe, Fabrizio, Ricci-Vitiani, Lucia, Pallini, Roberto, Di Pietro, Roberta, Di Iorio, Patrizia, Ascani, Giuliano, Ciccarelli, Renata, and Angelucci, Stefania
- Subjects
HUMAN stem cells ,EXTRACELLULAR vesicles ,BRAIN tumors ,GLIOBLASTOMA multiforme ,CELL motility ,PROTEOMICS - Abstract
Extracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies and poor patient prognosis. Given the high relevance of the information provided by cancer cell secretome, we performed a proteomic analysis of microvesicles (MVs) and exosomes (EXOs) released from GBM-derived stem cells (GSCs). The latter, obtained from the brain of GBM patients, expressed P2X7 receptors (P2X7Rs), which positively correlate with GBM growth and invasiveness. P2X7R stimulation of GSCs caused significant changes in the EV content, mostly ex novo inducing or upregulating the expression of proteins related to cytoskeleton reorganization, cell motility/spreading, energy supply, protection against oxidative stress, chromatin remodeling, and transcriptional regulation. Most of the induced/upregulated proteins have already been identified as GBM diagnostic/prognostic factors, while others have only been reported in peripheral tumors. Our findings indicate that P2X7R stimulation enhances the transport and, therefore, possible intercellular exchange of GBM aggressiveness-increasing proteins by GSC-derived EVs. Thus, P2X7Rs could be considered a new druggable target of human GBM, although these data need to be confirmed in larger experimental sets. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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130. Nasopharyngeal Carcinoma Cell Lines: Reliable Alternatives to Primary Nasopharyngeal Cells?
- Author
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Makowska, Anna and Weiskirchen, Ralf
- Subjects
NASOPHARYNX cancer ,SCIENTIFIC literature ,EXPERIMENTAL medicine ,HELA cells ,CELL motility - Abstract
Nasopharyngeal carcinoma (NPC) is a type of cancer that originates from the mucosal lining of the nasopharynx and can invade and spread. Although contemporary chemoradiotherapy effectively manages the disease locally, there are still challenges with locoregional recurrence and distant failure. Therefore, it is crucial to have a deeper understanding of the molecular basis of NPC cell movement in order to develop a more effective treatment and to improve patient survival rates. Cancer cell line models are invaluable in studying health and disease and it is not surprising that they play a critical role in NPC research. Consequently, scientists have established around 80 immortalized human NPC lines that are commonly used as in vitro models. However, over the years, it has been observed that many cell lines are misidentified or contaminated by other cells. This cross-contamination leads to the creation of false cell lines that no longer match the original donor. In this commentary, we discuss the impact of misidentified NPC cell lines on the scientific literature. We found 1159 articles from 2000 to 2023 that used NPC cell lines contaminated with HeLa cells. Alarmingly, the number of publications and citations using these contaminated cell lines continued to increase, even after information about the contamination was officially published. These articles were most commonly published in the fields of oncology, pharmacology, and experimental medicine research. These findings highlight the importance of science policy and support the need for journals to require authentication testing before publication. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
131. First person - Eike Mahlandt.
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CYTOSKELETON ,CELL motility ,VASCULAR endothelial cells ,LIFE sciences ,FLUORESCENT proteins - Published
- 2022
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132. First person - Shafali Gupta.
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LIFE sciences ,CELL imaging ,EMBRYOLOGY ,EPITHELIAL cells ,CELL motility - Published
- 2022
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133. On the qualitative analysis of the uniqueness of the movement of endothelial cells.
- Author
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Altuntaç, Erdem and Pamuk, Serdal
- Subjects
QUANTITATIVE research ,ENDOTHELIUM ,CELL motility ,FIBRONECTINS ,NEOVASCULARIZATION - Abstract
This paper extends the work of Pamuk (2003) by showing mathematically that the movement of endothelial cells, to the regions where active enzyme is large or where fibronectin is small, is unique. To do this, we obtain the existence and uniqueness of the steady-state solution of an initial-boundary value problem which mathematically models endothelial cell movement in tumor angiogenesis. A specific example showing the instability of this steady-state solution is provided. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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134. Live-Cell Tracking Using SIFT Features in DIC Microscopic Videos.
- Author
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Jiang, Richard M., Crookes, Danny, Nie Luo, and Davidson, Michael W.
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LAPLACIAN operator ,PRINCIPAL components analysis ,CELL motility ,MICROSCOPY ,BIOMEDICAL engineering - Abstract
In this paper, a novel motion-tracking scheme using scale-invariant features is proposed for automatic cell motility analysis in gray-scale microscopic videos, particularly for the live-cell tracking in low-contrast differential interference contrast (DIC) microscopy. In the proposed approach, scale-invariant feature transform (SIFT) points around live cells in the microscopic image are detected, and a structure locality preservation (SLP) scheme using Laplacian Eigenmap is proposed to track the SIFT feature points along successive frames of low-contrast DIC videos. Experiments on low-contrast DIC microscopic videos of various live-cell lines shows that in comparison with principal component analysis (PCA) based SIFT tracking, the proposed Laplacian-SIFT can significantly reduce the error rate of SIFT feature tracking. With this enhancement, further experimental results demonstrate that the proposed scheme is a robust and accurate approach to tackling the challenge of live-cell tracking in DIC microscopy. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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135. ON MODELING COMPLEX COLLECTIVE BEHAVIOR IN MYXOBACTERIA.
- Author
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Yi Jiang, Sozinova, Olga, and Alber, Mark
- Subjects
MYXOBACTERALES ,LATTICE gas ,CELLULAR automata ,CELL motility ,BACTERIAL spores ,CELL aggregation ,CHEMOTAXIS ,CELL communication - Abstract
This paper reviews recent progress in modeling collective behaviors in myxobacteria using lattice gas cellular automata approach (LGCA). Myxobacteria are social bacteria that swarm, glide on surfaces and feed cooperatively. When starved, tens of thousands of cells change their movement pattern from outward spreading to inward concentration; they form aggregates that become fruiting bodies. Cells inside fruiting bodies differentiate into round, nonmotile, environmentally resistant spores. Traditionally, cell aggregation has been considered to imply chemotaxis, a long-range cell interaction. However, myxobacteria aggregation is the consequence of direct cell-contact interactions, not chemotaxis. In this paper, we review biological LGCA models based on local cell–cell contact signaling that have reproduced the rippling, streaming, aggregating and sporulation stages of the fruiting body formation in myxobacteria. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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136. Unde venisti PGRMC? Grand-Scale Biology from Early Eukaryotes and Eumetazoan Animal Origins
- Author
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Michael A. Cahill
- Subjects
steroid biology ,eukaryogenesis ,membrane-associated progesterone receptor ,neurogenesis ,neurobiology ,synapse ,cyp51a1 ,candidate phyla radiation bacteria ,heme ,redox ,metabolism ,translational control ,eumetazoa ,eumetazoans ,leumca ,gastrulation ,gastrulation organizer ,blastoporal axial organizer ,pluripotent stem cells ,tmem97 ,sigma-2 receptor ,cell motility ,sleep ,epigenetics ,aging ,aging clock ,tyrosine phosphorylation ,epithelial-mesenchymal transition ,emt ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
The title usage of Unde venisti ‘from where have you come’ is from a now dead language (Latin) that foundationally influenced modern English (not the major influence, but an essential formative one). This is an apt analogy for how both the ancient eukaryotic and eumetazoan functions of PGRMC proteins (PGRMC1 and PGRMC2 in mammals) probably influence modern human biology: via a formative trajectory from an evolutionarily foundational fulcrum. There is an arguable probability, although not a certainty, that PGRMC-like proteins were involved in eukaryogenesis. If so, then the proto-eukaryotic ancestral protein is modelled as having initiated the oxygen-induced and CYP450 (Cytochrome P450)-mediated synthesis of sterols in the endoplasmic reticulum to regulate proto-mitochondrial activity and heme homeostasis, as well as having enabled sterol transport between endoplasmic reticulum (ER) and mitochondria membranes involving the actin cytoskeleton, transport of heme from mitochondria, and possibly the regulation/origins of mitosis/meiosis. Later, during animal evolution, the last eumetazoan common ancestor (LEUMCA) acquired PGRMC phosphorylated tyrosines coincidentally with the gastrulation organizer, Netrin/deleted in colorectal carcinoma (DCC) signaling, muscle fibers, synapsed neurons, and neural recovery via a sleep-like process. Modern PGRMC proteins regulate multiple functions, including CYP450-mediated steroidogenesis, membrane trafficking, heme homeostasis, glycolysis/Warburg effect, fatty acid metabolism, mitochondrial regulation, and genomic CpG epigenetic regulation of gene expression. The latter imposes the system of differentiation status-sensitive cell-type specific proteomic complements in multi-tissued descendants of the LEUMCA. This paper attempts to trace PGRMC functions through time, proposing that key functions were involved in early eukaryotes, and were later added upon in the LEUMCA. An accompanying paper considers the implications of this awareness for human health and disease.
- Published
- 2022
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137. Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease
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Michael A. Cahill
- Subjects
steroid biology ,eukaryogenesis ,membrane-associated progesterone receptor ,neurogenesis: neurobiology ,synapse ,cyp51a1 ,heme ,redox ,metabolism ,translational control ,eumetazoa ,eumetazoans ,leumca ,gastrulation ,gastrulation organizer ,blastoporal axial organizer ,pluripotent stem cells ,tmem97 ,sigma-2 receptor ,cell motility ,sleep ,epigenetics ,aging ,aging clock ,tyrosine phosphorylation ,epithelial-mesenchymal transition ,emt ,cancer ,diabetes ,intestinal microbiome ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
The title usage of Latin Quo vadis ‘where are you going’ extends the question Unde venisti from where ‘did you come?’ posed in the accompanying paper and extends consideration of how ancient eukaryotic and eumetazoan functions of progesterone receptor membrane component (PGRMC) proteins (PGRMC1 and PGRMC2 in mammals) could influence modern human health and disease. This paper attempts to extrapolate to modern biology in terms of extensions of hypothetical ancestral functional states from early eukaryotes and the last eumetazoan common ancestor (LEUMCA), to relativize human metabolic physiology and disease. As novel cell types and functional specializations appeared in bilaterian animals, PGRMC functions are hypothesized to have continued to be part of the toolkit used to develop new cell types and manage increasingly complex tasks such as nerve-gut-microbiome neuronal and hormonal communication. A critical role of PGRMC (as one component of a new eumetazoan genetic machinery) is proposed in LEUMCA endocrinology, neurogenesis, and nerve-gut communication with possible involvement in circadian nicotinamide adenine dinucleotide synthesis. This model would explain the contribution of PGRMC to metabolic and differentiation/behavioral changes observed in age-related diseases like diabetes, cancer and perhaps aging itself. Consistent with proposed key regulation of neurogenesis in the LEUMCA, it is argued that Alzheimer’s disease is the modern pathology that most closely reflects the suite of functions related to PGRMC biology, with the ‘usual suspect’ pathologies possibly being downstream of PGRMC1. Hopefully, these thoughts help to signpost directions for future research.
- Published
- 2022
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138. Tensor decomposition-based unsupervised feature extraction applied to matrix products for multi-view data processing.
- Author
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Taguchi, Y-h.
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BIODEGRADATION ,FEATURE extraction ,INFORMATION storage & retrieval systems ,MIXING ,COMBINATORIAL chemistry - Abstract
In the current era of big data, the amount of data available is continuously increasing. Both the number and types of samples, or features, are on the rise. The mixing of distinct features often makes interpretation more difficult. However, separate analysis of individual types requires subsequent integration. A tensor is a useful framework to deal with distinct types of features in an integrated manner without mixing them. On the other hand, tensor data is not easy to obtain since it requires the measurements of huge numbers of combinations of distinct features; if there are m kinds of features, each of which has N dimensions, the number of measurements needed are as many as N
m , which is often too large to measure. In this paper, I propose a new method where a tensor is generated from individual features without combinatorial measurements, and the generated tensor was decomposed back to matrices, by which unsupervised feature extraction was performed. In order to demonstrate the usefulness of the proposed strategy, it was applied to synthetic data, as well as three omics datasets. It outperformed other matrix-based methodologies. [ABSTRACT FROM AUTHOR]- Published
- 2017
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139. A new holistic 3D non-invasive analysis of cellular distribution and motility on fibroin-alginate microcarriers using light sheet fluorescent microscopy.
- Author
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Duchi, Serena, Piccinini, Filippo, Pierini, Michela, Bevilacqua, Alessandro, Torre, Maria Luisa, Lucarelli, Enrico, and Santi, Spartaco
- Subjects
THREE-dimensional imaging ,CELL communication ,BIOMATERIALS ,TISSUE engineering ,MESENCHYMAL stem cells ,FLUORESCENCE microscopy - Abstract
Cell interaction with biomaterials is one of the keystones to developing medical devices for tissue engineering applications. Biomaterials are the scaffolds that give three-dimensional support to the cells, and are vectors that deliver the cells to the injured tissue requiring repair. Features of biomaterials can influence the behaviour of the cells and consequently the efficacy of the tissue-engineered product. The adhesion, distribution and motility of the seeded cells onto the scaffold represent key aspects, and must be evaluated in vitro during the product development, especially when the efficacy of a specific tissue-engineered product depends on viable and functional cell loading. In this work, we propose a non-invasive and non-destructive imaging analysis for investigating motility, viability and distribution of Mesenchymal Stem Cells (MSCs) on silk fibroin-based alginate microcarriers, to test the adhesion capacity of the fibroin coating onto alginate which is known to be unsuitable for cell adhesion. However, in depth characterization of the biomaterial is beyond the scope of this paper. Scaffold-loaded MSCs were stained with Calcein-AM and Ethidium homodimer-1 to detect live and dead cells, respectively, and counterstained with Hoechst to label cell nuclei. Time-lapse Light Sheet Fluorescent Microscopy (LSFM) was then used to produce three-dimensional images of the entire cells-loaded fibroin/alginate microcarriers. In order to quantitatively track the cell motility over time, we also developed an open source user friendly software tool called Fluorescent Cell Tracker in Three-Dimensions (F-Tracker3D). Combining LSFM with F-Tracker3D we were able for the first time to assess the distribution and motility of stem cells in a non-invasive, non-destructive, quantitative, and three-dimensional analysis of the entire surface of the cell-loaded scaffold. We therefore propose this imaging technique as an innovative holistic tool for monitoring cell-biomaterial interactions, and as a tool for the design, fabrication and functionalization of a scaffold as a medical device. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
140. Lacking of palladin leads to multiple cellular events changes which contribute to NTD.
- Author
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Juan Tan, Xue-Jiao Chen, Chun-Ling Shen, Hong-Xin Zhang, Ling-Yun Tang, Shun-Yuan Lu, Wen-Ting Wu, Ying Kuang, Jian Fei, and Zhu-Gang Wang
- Subjects
NEURAL tube ,CELL motility ,CELL adhesion ,CYTOSKELETAL proteins ,CELL cycle ,PHYSIOLOGY - Abstract
Background: The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects. However, the mechanism how palladin regulates the process of cranial neural tube closure (NTC) remains unknown. Methods: In this paper, we use gene knockout mouse to elucidate the function of palladin in the regulation of NTC process. Results: We initially focuse on the expression pattern of palladin and found that in embryonic brain, palladin is predominantly expressed in the neural folds at E9.5. We further check the major cellular events in the neural epithelium that may contribute to NTC during the early embryogenesis. Palladin deficiency leads to a disturbance of cytoskeleton in the neural tube and the cultured neural progenitors. Furthermore, increased cell proliferation, decreased cell differentiation and diminished apical cell apoptosis of neural epithelium are found in palladin deficient embryos. Cell cycle of neural progenitors in Palladin
-/- embryos is much shorter than that in wt ones. Cell adhesion shows a reduction in Palladin-/- neural tubes. Conclusions: Palladin is expressed with proper spatio-temporal pattern in the neural folds. It plays a crucial role in regulating mouse cranial NTC by modulating cytoskeleton, proliferation, differentiation, apoptosis, and adhesion of neural epithelium. Our findings facilitate further study of the function of palladin and the underlying molecular mechanism involved in NTC. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
141. Oleanolic acid induces migration in Mv1Lu and MDA-MB-231 epithelial cells involving EGF receptor and MAP kinases activation.
- Author
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Bernabé-García, Ángel, Armero-Barranco, David, Liarte, Sergio, Ruzafa-Martínez, María, Ramos-Morcillo, Antonio Jesús, and Nicolás, Francisco José
- Subjects
SKIN wound treatment ,CELL migration ,MITOGEN-activated protein kinases ,EPIDERMAL growth factor receptors ,FLAVONOIDS ,WOUND healing - Abstract
During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo. In this paper, we pursued to disclose the molecular mechanisms underlying those effects, by using an in vitro scratch assay in two epithelial cell lines of different linage: non-malignant mink lung epithelial cells, Mv1Lu; and human breast cancer cells, MDA-MB-231. In every case, we observed that OA clearly enhanced cell migration for in vitro scratch closure. This correlated with the stimulation of molecular pathways related to mitogen-activated protein (MAP) kinases, as ERK1,2 and Jun N-terminal kinase (JNK) 1,2 activation and c-Jun phosphorylation. Moreover, MDA-MB-231 cells treated with OA displayed an altered gene expression profile affecting transcription factor genes (c-JUN) as well as proteins involved in migration and ECM dynamics (PAI1), in line with the development of an epithelial to mesenchymal transition (EMT) status. Strikingly, upon OA treatment, we observed changes in the epidermal growth factor receptor (EGFR) subcellular localization, while interfering with its signalling completely prevented migration effects. This data provides a physiological framework supporting the notion that lipophilic plant extracts used in traditional medicine, might modulate wound healing processes in vivo through its OA contents. The molecular implications of these observations are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
142. The role of myosin II in glioma invasion: A mathematical model.
- Author
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Lee, Wanho, Lim, Sookkyung, and Kim, Yangjin
- Subjects
NUCLEAR energy ,MYOSIN genetics ,PROTEIN genetics ,AMOEBOID movement ,BRAIN cancer diagnosis - Abstract
Gliomas are malignant tumors that are commonly observed in primary brain cancer. Glioma cells migrate through a dense network of normal cells in microenvironment and spread long distances within brain. In this paper we present a two-dimensional multiscale model in which a glioma cell is surrounded by normal cells and its migration is controlled by cell-mechanical components in the microenvironment via the regulation of myosin II in response to chemoattractants. Our simulation results show that the myosin II plays a key role in the deformation of the cell nucleus as the glioma cell passes through the narrow intercellular space smaller than its nuclear diameter. We also demonstrate that the coordination of biochemical and mechanical components within the cell enables a glioma cell to take the mode of amoeboid migration. This study sheds lights on the understanding of glioma infiltration through the narrow intercellular spaces and may provide a potential approach for the development of anti-invasion strategies via the injection of chemoattractants for localization. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
143. Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma.
- Author
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Gao, Xiao-lei, Wu, Jia-shun, Cao, Min-xin, Gao, Shi-yu, Cen, Xiao, Jiang, Ya-ping, Wang, Sha-sha, Tang, Ya-jie, Chen, Qian-ming, Liang, Xin-hua, and Tang, Yaling
- Subjects
KERATIN ,ADENOID cystic carcinoma ,METASTASIS ,IMMUNE response ,SMALL interfering RNA - Abstract
Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
144. The Flux of Euglena gracilis Cells Depends on the Gradient of Light Intensity.
- Author
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Ogawa, Takuma, Shoji, Erika, Suematsu, Nobuhiko J., Nishimori, Hiraku, Izumi, Shunsuke, Awazu, Akinori, and Iima, Makoto
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EUGLENA gracilis ,LIGHT intensity ,PHOTOTAXIS ,ALGAL cells ,CELL suspensions - Abstract
We have quantified the photomovement behavior of a suspension of Euglena gracilis representing a behavioral response to a light gradient. Despite recent measurements of phototaxis and photophobicity, the details of macroscopic behavior of cell photomovements under conditions of light intensity gradients, which are critical to understand recent experiments on spatially localized bioconvection patterns, have not been fully understood. In this paper, the flux of cell number density under a light intensity gradient was measured by the following two experiments. In the first experiment, a capillary containing the cell suspension was illuminated with different light intensities in two regions. In the steady state, the differences of the cell numbers in the two regions normalized by the total number were proportional to the light difference, where the light intensity difference ranged from 0.5–2.0 μmol m
−2 s−1 . The proportional coefficient was positive (i.e., the bright region contained many microorganisms) when the mean light intensity was weak (1.25 μmol m−2 s−1 ), whereas it was negative when the mean intensity was strong (13.75 μmol m−2 s−1 ). In the second experiment, a shallow rectangular container of the suspension was illuminated with stepwise light intensities. The cell number density distribution exhibited a single peak at the position where the light intensity was about Ic ≃ 3.8 μmol m−2 s−1 . These results suggest that the suspension of E. gracilis responded to the light gradient and that the favorable light intensity was Ic . [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
145. Ligand Activation of TAM Family Receptors-Implications for Tumor Biology and Therapeutic Response.
- Author
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Davra, Viralkumar, Kimani, Stanley G., Calianese, David, and Birge, Raymond B.
- Subjects
PROTEIN-tyrosine kinase inhibitors ,BLOOD proteins ,CANCER invasiveness ,CELL receptors ,CELL motility ,CHALONES ,LIGANDS (Biochemistry) ,METASTASIS ,MONOCLONAL antibodies ,PROTEIN-tyrosine kinases ,TUMORS ,EVIDENCE-based medicine ,THERAPEUTICS - Abstract
The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology. As a result, several classes of TAM inhibitors that include small molecule tyrosine kinase inhibitors, monoclonal antibodies, decoy receptors, as well as novel strategies to target TAM ligands are being developed. This paper will review the biology of TAM receptors and their ligands with a focus on cancer, as well as evidence-based data for the continued pursuit of TAM/Gas6 inhibitors in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
146. The Development Of Drosophila Melanogaster under Different Duration Space Flight and Subsequent Adaptation to Earth Gravity.
- Author
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Ogneva, Irina V., Belyakin, Stepan N., and Sarantseva, Svetlana V.
- Subjects
MORPHOGENESIS ,DROSOPHILA melanogaster ,SPACE flight ,EARTH gravitation ,GENETIC transcription ,CYTOSKELETAL proteins ,CELL motility - Abstract
In prospective human exploration of outer space, the need to preserve a species over several generations under changed gravity conditions may arise. This paper demonstrates our results in the creation of the third generation of fruit fly Drosophila melanogaster (third-stage larvae) during the 44.5-day space flight (Foton-M4 satellite (2014, Russia)), then the fourth generation on Earth and the fifth generation again in conditions of the 12-day space flight (2014, in the Russian Segment of the ISS). The species preserves fertility despite a number of changes in the level of expression and content of cytoskeletal proteins, which are the key components of the cleavage spindle and the contractile ring of cells. The results of transcriptome screening and space analysis of cytoskeletal proteins show that the exposure to weightless conditions leads to the increased transcription of metabolic genes, cuticle components and the decreased transcription of genes involved in morphogenesis, cell differentiation, cytoskeletal organization and genes associated with the plasma membrane. “Subsequent” exposure to the microgravity for 12 days resulted in an even more significant increase/decrease in the transcription of the same genes. On the contrary, the transition from the microgravity conditions to the gravity of Earth leads to the increased transcription of genes whose products are involved in the morphogenesis, cytoskeletal organization, motility of cells and transcription regulation, and to the decreased transcription of cuticle genes and proteolytic processes. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
147. CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.
- Author
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Walck-Shannon, Elise, Cochran, Hunter, Bothfeld, William, Hardin, Jeff, Lucas, Bethany, Chin-Sang, Ian, Reiner, David, and Kumfer, Kraig
- Subjects
CELL migration ,EPITHELIAL cells ,INTERCALATION reactions ,EPIDERMIS ,MORPHOGENESIS - Abstract
Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
148. An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.
- Author
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Wang, Zi, Ramsey, Benjamin J., Wang, Dali, Wong, Kwai, Li, Husheng, Wang, Eric, and Bao, Zhirong
- Subjects
MULTIAGENT systems ,CAENORHABDITIS elegans ,EMBRYOLOGY ,IMAGE analysis ,CELLS ,CELL motility ,CELL communication ,BEHAVIOR - Abstract
With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact in vivo to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study C. elegans embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
149. Reaction-Diffusion on a Spatial Mathematical Model of Cancer Immunotherapy with Effector Cells and IL-2 Compounds' Interactions.
- Author
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Suddin, Sulasri, Adi-Kusumo, Fajar, Aryati, Lina, and Gunardi
- Subjects
- *
CELL populations , *IMMUNOTHERAPY , *CELL motility , *MATHEMATICAL models , *IMMUNE system - Abstract
Immunotherapy is one of the future treatments applicable in most cases of cancer including malignant cancer. Malignant cancer usually prevents some genes, e.g., p53 and pRb, from controlling the activation of the cell division and the cell apoptosis. In this paper, we consider the interactions among the cancer cell population, the effector cell population that is a part of the immune system, and cytokines that can be used to stimulate the effector cells called the IL-2 compounds. These interactions depend on both time and spatial position of the cells in the tissue. Mathematically, the spatial movement of the cells is represented by the diffusion terms. We provide an analytical study for the constant equilibria of the reaction-diffusion system describing the above interactions, which show the initial behaviour of the tissue, and we conduct numerical simulation that shows the dynamics along the tissue that represent the immunotherapy effects. In this case, we also consider the steady-state conditions of the system that show the long-time behaviour of these interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
150. Geometric regulation of collective cell tangential ordering migration.
- Author
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Dong, Hao, Zhou, Yuming, Ma, Xuehe, Liu, Junfang, Xing, Fulin, Yang, Jianyu, Sun, Qiushuo, Hu, Qingsong, Hu, Fen, Pan, Leiting, and Xu, Jingjun
- Subjects
CELLULAR control mechanisms ,POTTS model ,CELL migration ,CELL motility ,GEOMETRIC shapes - Abstract
Collective cell migration is a coordinated movement of multi-cell systems essential for various processes throughout life. The collective motions often occur under spatial restrictions, hallmarked by the collective rotation of epithelial cells confined in circular substrates. Here, we aim to explore how geometric shapes of confinement regulate this collective cell movement. We develop quantitative methods for cell velocity orientation analysis, and find that boundary cells exhibit stronger tangential ordering migration than inner cells in circular pattern. Furthermore, decreased tangential ordering movement capability of collective cells in triangular and square patterns are observed, due to the disturbance of cell motion at unsmooth corners of these patterns. On the other hand, the collective cell rotation is slightly affected by a convex defect of the circular pattern, while almost hindered with a concave defect, also resulting from different smoothness features of their boundaries. Numerical simulations employing cell Potts model well reproduce and extend experimental observations. Together, our results highlight the importance of boundary smoothness in the regulation of collective cell tangential ordering migration. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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