scholarly journals Localization and distribution of nickel and other elements in in-vitro grown Alyssum corsicum exhibiting morphological changes in trichomes: initial insights into molecular mechanisms of nickel hyperaccumulation

2013 ◽  
Vol 37 ◽  
pp. 1115-1124 ◽  
Author(s):  
Seniha Selcen BABAOĞLU AYDAŞ ◽  
Leyla AÇIK ◽  
Danika LEDUC ◽  
Nezaket ADIGÜZEL ◽  
Şeküre Şebnem ELLİALTIOĞLU ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Nickel Hyperaccumulation

scholarly journals Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Satoshi Takagi ◽  
Yuki Sasaki ◽  
Sumie Koike ◽  
Ai Takemoto ◽  
Yosuke Seto ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Pulmonary Metastasis ◽  
Lysophosphatidic Acid ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Platelet Releasate

AbstractOsteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.

scholarly journals Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1497
Author(s):  
Luz del Mar Rivas-Chacón ◽  
Sofía Martínez-Rodríguez ◽  
Raquel Madrid-García ◽  
Joaquín Yanes-Díaz ◽  
Juan Ignacio Riestra-Ayora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Damage ◽  
Stria Vascularis ◽  
Organ Of Corti ◽  
Age Related ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL) is an increasing and gradual sensorineural hearing dysfunction. Oxidative stress is an essential factor in developing ARHL; additionally, premature senescence of auditory cells induced by oxidative stress can produce hearing loss. Hydrogen peroxide (H2O2) represents a method commonly used to generate cellular senescence in vitro. The objective of the present paper is to study H2O2-induced senescence patterns in three auditory cell lines (House Ear Institute-Organ of Corti 1, HEI-OC1; organ of Corti, OC-k3, and stria vascularis, SV-k1 cells) to elucidate the intrinsic mechanisms responsible for ARHL. The auditory cells were exposed to H2O2 at different concentrations and times. The results obtained show different responses of the hearing cells concerning cell growth, β-galactosidase activity, morphological changes, mitochondrial activation, levels of oxidative stress, and other markers of cell damage (Forkhead box O3a, FoxO3a, and 8-oxoguanine, 8-oxoG). Comparison between the responses of these auditory cells to H2O2 is a helpful method to evaluate the molecular mechanisms responsible for these auditory cells’ senescence. Furthermore, this in vitro model could help develop anti-senescent therapeutic strategies for the treatment of AHRL.

102. CHARACTERISATION OF THE GTPase DYNAMIN THROUGHOUT MURINE SPERM MATURATION

2010 ◽  
Vol 22 (9) ◽  
pp. 20
Author(s):  
A. T. Reid ◽  
S. D. Roman ◽  
R. Aitken ◽  
B. Nixon
Keyword(s):  
Protein Trafficking ◽  
Molecular Mechanisms ◽  
Protein Translocation ◽  
Morphological Changes ◽  
Sperm Maturation ◽  
The Novel ◽  
Epididymal Maturation ◽  
Distinct Cell ◽  
Molecular Machinery

Throughout sperm maturation distinct remodelling events occur that imbue the cells with both the ability to bind the zona pellucida and undergo the acrosome reaction. Of long standing interest to our laboratory is the elucidation of the molecular mechanisms that underpin the attainment of these key functional attributes. This process begins with a complex range of morphological changes that accompany spermatogenesis, and is continued through post-testicular phases of maturation in both the male (epididymal maturation) and female (capacitation) reproductive tracts. However, among these changes only those occurring during the initial stages of spermatogenesis are intrinsically driven. The fact that the majority of sperm remodelling is extrinsically stimulated, and occurs in the absence of new protein synthesis, highlights the potential importance of processes such as intracellular protein trafficking. This has directed our focus towards the dynamin family of protein traffickers. The GTPase dynamin exists in three isoforms, namely Dnm1, Dnm2 and Dnm3 and is an integral part of the molecular machinery required for vesicle mediated protein translocation. Recent research from our laboratory has demonstrated the presence of these three isoforms in distinct, cell-specific locations during murine spermatogenesis. Immunofluorescence on mouse testis revealed that both Dnm1 and 2 are present within a region corresponding to the developing acrosome in maturing sperm, whilst Dnm3 appears to reside solely within pre-meiotic germ cells. Interestingly, Dnm1 and Dnm2 are both retained within the peri-acrosomal region of the sperm head in mature spermatozoa. Additionally, upon the induction of capacitation in vitro, staining for both Dnm1 and 2 becomes significantly reduced. Collectively these data support the novel hypothesis that dynamin not only participates in sperm remodelling events during spermatogenesis but may also have a previously unappreciated role in capacitation-associated priming of the sperm surface for interaction with the oocyte.

scholarly journals New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids

2021 ◽  
Author(s):  
Daniela Rodrigues ◽  
Terezinha de Souza ◽  
Luke Coyle ◽  
Matteo Di Piazza ◽  
Bram Herpers ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Cell Signalling ◽  
Mrna Translation ◽  
Atp Synthesis ◽  
Metabolome Analysis ◽  
Tissue Specific ◽  
Intestinal Toxicity

Abstract5-Fluorouracil (5-FU) is a widely used chemotherapeutical that induces acute toxicity in the small and large intestine of patients. Symptoms can be severe and lead to the interruption of cancer treatments. However, there is limited understanding of the molecular mechanisms underlying 5-FU-induced intestinal toxicity. In this study, well-established 3D organoid models of human colon and small intestine (SI) were used to characterize 5-FU transcriptomic and metabolomic responses. Clinically relevant 5-FU concentrations for in vitro testing in organoids were established using physiologically based pharmacokinetic simulation of dosing regimens recommended for cancer patients, resulting in exposures to 10, 100 and 1000 µM. After treatment, different measurements were performed: cell viability and apoptosis; image analysis of cell morphological changes; RNA sequencing; and metabolome analysis of supernatant from organoids cultures. Based on analysis of the differentially expressed genes, the most prominent molecular pathways affected by 5-FU included cell cycle, p53 signalling, mitochondrial ATP synthesis and apoptosis. Short time-series expression miner demonstrated tissue-specific mechanisms affected by 5-FU, namely biosynthesis and transport of small molecules, and mRNA translation for colon; cell signalling mediated by Rho GTPases and fork-head box transcription factors for SI. Metabolomic analysis showed that in addition to the effects on TCA cycle and oxidative stress in both organoids, tissue-specific metabolic alterations were also induced by 5-FU. Multi-omics integration identified transcription factor E2F1, a regulator of cell cycle and apoptosis, as the best key node across all samples. These results provide new insights into 5-FU toxicity mechanisms and underline the relevance of human organoid models in the safety assessment in drug development.

scholarly journals Molecular Signatures of Self-Renewal, Differentiation, and Lineage Choice in Multipotential Hemopoietic Progenitor Cells In Vitro

2004 ◽  
Vol 24 (2) ◽  
pp. 741-756 ◽  
Author(s):  
Ludovica Bruno ◽  
Reinhard Hoffmann ◽  
Fraser McBlane ◽  
John Brown ◽  
Rajeev Gupta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Self Renewal ◽  
Cell Fate Decisions ◽  
Hemopoietic Progenitor ◽  
Hemopoietic Progenitor Cells

ABSTRACT The molecular mechanisms governing self-renewal, differentiation, and lineage specification remain unknown. Transcriptional profiling is likely to provide insight into these processes but, as yet, has been confined to “static” molecular profiles of stem and progenitors cells. We now provide a comprehensive, statistically robust, and “dynamic” analysis of multipotent hemopoietic progenitor cells undergoing self-renewal in response to interleukin-3 (IL-3) and multilineage differentiation in response to lineage-affiliated cytokines. Cells undergoing IL-3-dependent proliferative self-renewal displayed striking complexity, including expression of genes associated with different lineage programs, suggesting a highly responsive compartment poised to rapidly execute intrinsically or extrinsically initiated cell fate decisions. A remarkable general feature of early differentiation was a resolution of complexity through the downregulation of gene expression. Although effector genes characteristic of mature cells were upregulated late, coincident with morphological changes, lineage-specific changes in gene expression were observed prior to this, identifying genes which may provide early harbingers of unilineage commitment. Of particular interest were genes that displayed differential behavior irrespective of the lineage elaborated, many of which were rapidly downregulated within 4 to 8 h after exposure to a differentiation cue. These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se.

scholarly journals The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study

2020 ◽  
pp. 88-98
Author(s):  
Rand R. Hafidh ◽  
Ahmed S. Abdulamir
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Future Research ◽  
Cycle Arrest

Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment with Carnosol was investigated by qRT-PCR. Up to 80% of the treated cells with Carnosol IC50 underwent apoptosis. Apoptosis together with cell cycle arrest in G0/G1 phase were induced significantly after treatment with Carnosol IC50. Fifteen out of nineteen genes studied were found to be remarkably up- or down- regulated after treatment with Carnosol. Six up-regulated genes (EREG, FOS-2, ID2, CRYAB, DUSP5, and TICAM2) and nine down-regulated genes (FN1, KRAS2, CCNB1-1, FEN1, MCM4, MCM5, GTSE1, CXCL1, and RALA) were recorded. These genes are candidates for future research for elucidating anticancer molecular targeted therapies, cancerous signaling and cancer development pathways in cervical cancer; moreover, elucidating the role of apoptosis, inflammation, cell proliferation, and cell differentiation in the development of cervical cancer.

scholarly journals Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 367 ◽  
Author(s):  
Hui Shi ◽  
Xiao-Long Wang ◽  
Hong-Feng Quan ◽  
Lin Yan ◽  
Xiu-Ying Pei ◽  
...  
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Arginase 1 ◽  
Iκb Kinase ◽  
Anti Inflammatory

Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.

scholarly journals Combinatorial Cytotoxic Effects of Gelam Honey and 5-Fluorouracil against Human Adenocarcinoma Colon Cancer HT-29 Cells In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Syed Ahmad Tajudin T-Johari ◽  
Fatimah Hashim ◽  
Wan Iryani Ismail ◽  
Abdul Manaf Ali
Keyword(s):  
Cytotoxic Effect ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Combined Treatment ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Diphenyltetrazolium Bromide ◽  
Gelam Honey ◽  
Ht 29

Combination of natural products with chemodrugs is becoming a trend in discovering new therapeutics approach for enhancing the cancer treatment process. In the present study, we aimed to investigate the cytotoxic and apoptosis induction of Gelam honey (GH) combined with or without 5-Fluorouracil (5-FU) on HT-29 cells. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to assess cytotoxicity. Morphological changes and apoptosis were determined by the inverted microscope, Annexin V-FITC, and DNA fragmentation via flow cytometric analysis, respectively. Our results demonstrate that combined treatment revealed a remarkable and concentration-dependent cytotoxic effect on HT-29 cells in comparison with GH and 5-FU alone. Flow cytometry analysis showed that early apoptosis event was more pronounced in combined treatment. In addition, compared to 5-FU alone, apoptosis of HT-29 cells treated with combinations of GH and 5-FU demonstrated increasing percentages of fragmented DNA. Our results suggest that GH has a synergistic cytotoxic effect with 5-FU in HT-29 cell lines in vitro. Although the actions of the molecular mechanisms are not yet clear, the results reveal that the combination of GH and 5-FU could have the potential as a therapeutic agent.

scholarly journals miR-200 Regulates Endometrial Development During Early Pregnancy

2016 ◽  
Vol 30 (9) ◽  
pp. 977-987 ◽  
Author(s):  
Patricia T. Jimenez ◽  
Monica A. Mainigi ◽  
R. Ann Word ◽  
W. Lee Kraus ◽  
Carole R. Mendelson
Keyword(s):  
Zinc Finger ◽  
Early Pregnancy ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Embryo Implantation ◽  
Endometrial Stromal Cells ◽  
E Box ◽  
Mesenchymal Epithelial Transition

Abstract For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated. Conversely, miR-200 was up-regulated during in vitro decidualization of human endometrial stromal cells. Knockdown of miR-200 negatively affected decidualization and prevented the mesenchymal-epithelial transition-like changes that accompanied decidual differentiation. Notably, superovulation of mice and humans altered miR-200 expression. Our findings suggest that hormonal alterations that accompany superovulation may negatively impact endometrial development and decidualization by causing aberrant miR-200 expression.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

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