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Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 128
Author(s):  
Lixia Chen ◽  
Yang Zhang ◽  
Xinming Zhang ◽  
Ruijuan Lv ◽  
Rongtian Sheng ◽  
...  

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.


2021 ◽  
Vol 11 (40) ◽  
pp. 147-147
Author(s):  
Anisur Rahman Khuda-Bukhsh

The mechanism of action of the potentized homeopathic drugs, particularly those diluted beyond Avogadro’s limit, is still a debatable issue and various hypotheses in this regard have been advocated by many. In our studies since 1980, we found that certain ultra-highly diluted homeopathic remedies could produce ameliorative effects in various model test organisms like bacteria, fungus, mice and human beings, while the succussed alcohol (placebo) could not. These drugs could antagonize/ameliorate several types of experimentally induced tumors/cancers in mice as evident from electron microscopic studies and certain specific cancer biomarkers. They also demonstrated significant effect on cell viability and apoptotic effect (mostly mitochondria mediated) on cancer cells in culture (also in experimental mice), as revealed from various assays like AnnexinV-FITC, TUNEL, DNA fragmentation, DAPI, COMET, HOECHST 33258, Rhodamine 123 etc while the succussed alcohol (“vehicle”) failed to show such effect. Expression of some key signal proteins and mRNA expressions like Bcl2 family proteins, Cytochrome c, Apaf 1, PARP, Caspase family, p53 and p38 etc in experimental mice model could be modulated by potentized homeopathic drugs. Under arsenic stress, the bacterium Escherichia coli, and the fungus Saccharomyces cerevisiae, and macrophage cells in culture responded favorably to the treatment of potentized homeopathic drug, Arsenicum Album 30C and homeopathically prepared Glucose 30C, as evident from modulation of several parameters like ROS accumulation, SOD activity, lipid peroxidation and expression level of certain relevant genes (Ars B, pts-G genes using real-time PCR) denoting detoxification, mainly via arsenic removal mechanism and suitable enzymatic modulation. Ultra-highly diluted potentized drugs (at potency 30C or above) could demonstrate protective changes simultaneously in multiple parameters (most of them under genetic control) of study, and their action continued for sometime even after the drugs were withdrawn; this indicates the ability of the drugs to trigger “gene action” involving up-regulation or down-regulation of a cascade of downstream genes, getting the recovery process into motion. The convincing evidences that support a “gene regulatory hypothesis” to explain the molecular mechanisms of action of the potentized drugs will be discussed in the light of some of our recent experimental findings on fungus, bacteria and bacteriophages.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kristin M Sherrard ◽  
Maureen Cetera ◽  
Sally Horne-Badovinac

Stress fibers (SFs) are actomyosin bundles commonly found in individually migrating cells in culture. However, whether and how cells use SFs to migrate in vivo or collectively is largely unknown. Studying the collective migration of the follicular epithelial cells in Drosophila, we found that the SFs in these cells show a novel treadmilling behavior that allows them to persist as the cells migrate over multiple cell lengths. Treadmilling SFs grow at their fronts by adding new integrin-based adhesions and actomyosin segments over time. This causes the SFs to have many internal adhesions along their lengths, instead of adhesions only at the ends. The front-forming adhesions remain stationary relative to the substrate and typically disassemble as the cell rear approaches. By contrast, a different type of adhesion forms at the SF’s terminus that slides with the cell’s trailing edge as the actomyosin ahead of it shortens. We further show that SF treadmilling depends on cell movement and identify a developmental switch in the formins that mediate SF assembly, with Dishevelled-associated activator of morphogenesis acting during migratory stages and Diaphanous acting during postmigratory stages. We propose that treadmilling SFs keep each cell on a linear trajectory, thereby promoting the collective motility required for epithelial migration.


Author(s):  
Yasuhito Tokumoto ◽  
Yasuto Araki ◽  
Yusuke Narizuka ◽  
Yosuke Mizuno ◽  
Susumu Ohshima ◽  
...  

Abstract Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here we describe a method to produce human memory-like T cells from naïve human T cells in culture. Using commercially available human T cell differentiation kits, both purified naïve CD8 + T cells and purified naïve CD4 + T cells were activated via T cell receptor signaling and appropriate cytokines for several days in culture. All the T cell activators were then removed from the medium and the cultures were continued in hypoxic condition (1% O2 atmosphere) for several more days; during this period, most of the cells died, but some survived in a quiescent state for a month. The survivors had small round cell bodies, expressed differentiation markers characteristic of memory T cells and restarted proliferation when the T cell activators were added back. We could also induce memory-like T cells from naïve human T cells without hypoxia, if we froze the activated T cells or prepared the naïve T cells from chilled filter buffy coats.


2021 ◽  
Author(s):  
Shino Takii ◽  
Jun Wu ◽  
Daiji Okamura

Serum-containing medium is widely used to support cell attachment, stable growth and serial passaging of various cancer cell lines.   However, the presence of cholesterols and lipids in serum greatly hinders the analysis of the effects of cholesterol depletion on cells in culture.   In this study, we develop a defined serum-free culture condition accessible to a variety of different types of adherent cancer cells. We tested different factors that are considered essential for cell culture and various extracellular matrix for plate coating, and found cells cultured in Dulbecco's Modified Eagle's Medium (DMEM) basal media supplemented with Albumin (BSA) and insulin-transferrin-selenium-ethanolamine (ITS-X) on fibronectin-precoated well (called as “DA-X condition”) showed comparable proliferation and survival to those in a serum-containing medium. Interestingly, we observed that DA-X condition could be adapted to a wide variety of adherent cancer cell lines, which enabled the analysis of how cholesterol depletion affected cancer cells in culture. Mechanistically, we found the beneficial effects of the DA-X condition in part can be attributed to the appropriate level of membrane cholesterol, and fibronectin-mediated signaling plays an important role in the suppression of cholesterol production.


2021 ◽  
Author(s):  
Kristin Sherrard ◽  
Maureen Cetera ◽  
Sally Horne-Badovinac

Stress fibers (SFs) are actomyosin bundles commonly found in individually migrating cells in culture. However, whether and how cells use SFs to migrate in vivo or collectively is largely unknown. Studying the collective migration of the follicular epithelial cells in Drosophila, we found that the SFs in these cells show a novel treadmilling behavior that allows them to persist as the cells migrate over multiple cell lengths. Treadmilling SFs grow at their fronts by adding new integrin-based adhesions and actomyosin segments over time. This causes the SFs to have many internal adhesions along their lengths, instead of adhesions only at the ends. The front-forming adhesions remain stationary relative to the substrate and typically disassemble as the cell rear approaches. By contrast, a different type of adhesion forms at the terminus of the SF that slides with the trailing edge of the cell as the actomyosin ahead of it shortens. We further show that SF treadmilling depends on cell movement and identify a developmental switch in the formins that mediate SF assembly, with DAAM acting during migratory stages and Diaphanous acting during post-migratory stages. We propose that treadmilling SFs keep each cell on a linear trajectory, thereby promoting the collective motility required for epithelial migration.


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