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IMA Fungus Aug 2023During the construction and assembly of the Mars 2020 mission components at two different NASA cleanrooms, several fungal strains were isolated. Based on their colony...
During the construction and assembly of the Mars 2020 mission components at two different NASA cleanrooms, several fungal strains were isolated. Based on their colony morphology, two strains that showed yeast-like appearance were further characterized for their phylogenetic position. The species-level classification of these two novel strains, using traditional colony and cell morphology methods combined with the phylogenetic reconstructions using multi-locus sequence analysis (MLSA) based on several gene loci (ITS, LSU, SSU, RPB1, RPB2, CYTB and TEF1), and whole genome sequencing (WGS) was carried out. This polyphasic taxonomic approach supported the conclusion that the two basidiomycetous yeasts belong to hitherto undescribed species. The strain FJI-L2-BK-P3, isolated from the Jet Propulsion Laboratory Spacecraft Assembly Facility, was placed in the Naganishia albida clade (Filobasidiales, Tremellomycetes), but is genetically and physiologically different from other members of the clade. Another yeast strain FKI-L6-BK-PAB1, isolated from the Kennedy Space Center Payload Hazardous and Servicing Facility, was placed in the genus Cystobasidium (Cystobasidiales, Cystobasidiomycetes) and is distantly related to C. benthicum. Here we propose two novel species with the type strains, Naganishia kalamii sp. nov. (FJI-L2-BK-P3 = NRRL 64466 = DSM 115730) and Cystobasidium onofrii sp. nov. (FKI-L6-BK-PAB1 = NRRL 64426 = DSM 114625). The phylogenetic analyses revealed that single gene phylogenies (ITS or LSU) were not conclusive, and MLSA and WGS-based phylogenies were more advantageous for species discrimination in the two genera. The genomic analysis predicted proteins associated with dehydration and desiccation stress-response and the presence of genes that are directly related to osmotolerance and psychrotolerance in both novel yeasts described. Cells of these two newly-described yeasts were exposed to UV-C radiation and compared with N. onofrii, an extremophilic UV-C resistant cold-adapted Alpine yeast. Both novel species were UV resistant, emphasizing the need for collecting and characterizing extremotolerant microbes, including yeasts, to improve microbial reduction techniques used in NASA planetary protection programs.
PubMed: 37568226
DOI: 10.1186/s43008-023-00119-4 -
Journal of Radiation Research Sep 2023Radiotherapy is one of the cornerstone of the glioblastoma treatment paradigm. However, the resistance of tumor cells to radiation results in poor survival. The...
Radiotherapy is one of the cornerstone of the glioblastoma treatment paradigm. However, the resistance of tumor cells to radiation results in poor survival. The mechanism of radioresistance has not been fully elucidated. This study aimed to screen the differential expressed genes related with radiosensitivity. The differentially expressed genes were screened based on RNA sequencing in 15 pairs of primary and recurrent glioblastoma that have undergone radiotherapy. Candidate genes were validated in 226 primary and 134 recurrent glioblastoma (GBM) obtained from the Chinese Glioma Genome Atlas (CGGA) database. RNA and protein expression were verified by Quantitative Real-time PCR (qPCR) and western blot in irradiated GBM cell lines. The candidate gene was investigated to explore the relationship between mRNA levels and clinical characteristics in the CGGA and The Cancer Genome Atlas dataset. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. Gene ontology and KEGG pathway analysis were used for bioinformatics analysis. Four genes (TMEM59L, Gelsolin, ZBTB7A and ATX) were screened. TMEM59L expression was significantly elevated in recurrent glioblastoma and lower in normal brain tissue. We selected TMEM59L as the target gene for further study. The increasing of TMEM59L expression induced by radiation was confirmed by mRNA and western blot in irradiated GBM cell. Further investigation revealed that high expression of TMEM59L was enriched in IDH mutant and MGMT methylated gliomas and associated with a better prognosis. Gene ontology and KEGG pathway analysis revealed that TMEM59L was closely related to the DNA damage repair and oxidative stress respond process. We speculated that the high expression of TMEM59L might enhance radiotherapy sensitivity by increasing ROS-induced DNA damage and inhibiting DNA damage repair process.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Brain Neoplasms; Transcription Factors; Neoplasm Recurrence, Local; DNA-Binding Proteins; Glioma; RNA, Messenger; Radiation Tolerance
PubMed: 37439405
DOI: 10.1093/jrr/rrad053 -
Phytomedicine : International Journal... Mar 2024In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage,...
BACKGROUND
In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism.
PURPOSE
This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated.
METHODS
The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis.
RESULTS
At a concentration of 25 μM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage.
CONCLUSION
This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.
Topics: Mice; Animals; Lung Neoplasms; Vascular Endothelial Growth Factor A; Mice, Nude; Cell Line, Tumor; Mice, Inbred C57BL; Vascular Endothelial Growth Factors; Radiation Tolerance; Radiation-Sensitizing Agents; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Glucosides; Isoflavones
PubMed: 38308918
DOI: 10.1016/j.phymed.2023.155290 -
NPJ Microgravity Feb 2024Recent growth in space systems has seen increasing capabilities packed into smaller and lighter Earth observation and deep space mission spacecraft. Phase-change... (Review)
Review
Recent growth in space systems has seen increasing capabilities packed into smaller and lighter Earth observation and deep space mission spacecraft. Phase-change materials (PCMs) are nonvolatile, reconfigurable, fast-switching, and have recently shown a high degree of space radiation tolerance, thereby making them an attractive materials platform for spaceborne photonics applications. They promise robust, lightweight, and energy-efficient reconfigurable optical systems whose functions can be dynamically defined on-demand and on-orbit to deliver enhanced science or mission support in harsh environments on lean power budgets. This comment aims to discuss the recent advances in rapidly growing PCM research and its potential to transition from conventional terrestrial optoelectronics materials platforms to versatile spaceborne photonic materials platforms for current and next-generation space and science missions. Materials International Space Station Experiment-14 (MISSE-14) mission-flown PCMs outside of the International Space Station (ISS) and key results and NASA examples are highlighted to provide strong evidence of the applicability of spaceborne photonics.
PubMed: 38378811
DOI: 10.1038/s41526-024-00358-8 -
Cell Death & Disease Dec 2023Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still...
Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.
Topics: Humans; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Regulation, Neoplastic; Hippo Signaling Pathway; Kinesins; Radiation Tolerance; YY1 Transcription Factor
PubMed: 38065955
DOI: 10.1038/s41419-023-06321-x -
Advanced Science (Weinheim,... Apr 2024Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of...
Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of sensitivity of HCC to this therapy is urgently required. It is demonstrated that RECQL4 is upregulated in the malignant cells of patients with HCC. Elevated RECQL4 levels reduce the sensitivity of HCC to radiotherapy by repairing radiation-induced double-stranded DNA (dsDNA) fragments. Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8 T cells in the tumor microenvironment (TME). RECQL4 disrupts the radiation-induced transformation of the TME into a tumoricidal niche by inhibiting the cGAS-STING pathway in dendritic cells. Knocking out STING in dendritic cells can block the impact of RECQL4 on HCC radiosensitivity. Notably, high RECQL4 expressions in HCC is significantly associated with poor prognosis in multiple independent cohorts. In conclusion, this study highlights how HCC-derived RECQL4 disrupts cGAS-STING pathway activation in dendritic cells through DNA repair, thus reducing the radiosensitivity of HCC. These findings provide new perspectives on the clinical treatment of HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Nucleotidyltransferases; Humans; Membrane Proteins; Mice; Animals; RecQ Helicases; Signal Transduction; Tumor Microenvironment; Dendritic Cells; Disease Models, Animal; Radiation Tolerance; Cell Line, Tumor
PubMed: 38381090
DOI: 10.1002/advs.202308009 -
Journal of Cancer Research and Clinical... Aug 2023Radiotherapy is a mainstay of cancer treatment. Clinical studies revealed a heterogenous response to radiotherapy, from a complete response to even disease progression.... (Review)
Review
INTRODUCTION
Radiotherapy is a mainstay of cancer treatment. Clinical studies revealed a heterogenous response to radiotherapy, from a complete response to even disease progression. To that end, finding the relative prognostic factors of disease outcomes and predictive factors of treatment efficacy and toxicity is essential. It has been demonstrated that radiation response depends on DNA damage response, cell cycle phase, oxygen concentration, and growth rate. Emerging evidence suggests that altered mitochondrial metabolism is associated with radioresistance.
METHODS
This article provides a comprehensive evaluation of the role of mitochondria in radiotherapy efficacy and toxicity. In addition, it demonstrates how mitochondria might be involved in the famous 6Rs of radiobiology.
RESULTS
In terms of this idea, decreasing the mitochondrial metabolism of cancer cells may increase radiation response, and enhancing the mitochondrial metabolism of normal cells may reduce radiation toxicity. Enhancing the normal cells (including immune cells) mitochondrial metabolism can potentially improve the tumor response by enhancing immune reactivation. Future studies are invited to examine the impacts of mitochondrial metabolism on radiation efficacy and toxicity. Improving radiotherapy response with diminishing cancer cells' mitochondrial metabolism, and reducing radiotherapy toxicity with enhancing normal cells' mitochondrial metabolism.
Topics: Humans; Mitochondria; Radiobiology; Neoplasms; Radiation Oncology; Biomarkers; Radiation Injuries; Radiation Tolerance; Radiotherapy
PubMed: 36719474
DOI: 10.1007/s00432-023-04592-7 -
Clinical & Translational Oncology :... Aug 2023Radiotherapy is one of the main therapies for cancer. The process leading to radioresistance is still not fully understood. Cancer radiosensitivity is related to the DNA... (Review)
Review
Radiotherapy is one of the main therapies for cancer. The process leading to radioresistance is still not fully understood. Cancer radiosensitivity is related to the DNA reparation of cancer cells and the tumor microenvironment (TME), which supports cancer cell survival. Factors that affect DNA reparation and the TME can directly or indirectly affect the radiosensitivity of cancer. Recent studies have shown that lipid metabolism in cancer cells, which is involved in the stability of cell membrane structure, energy supply and signal transduction of cancer cells, can also affect the phenotype and function of immune cells and stromal cells in the TME. In this review, we discussed the effects of lipid metabolism on the radiobiological characteristics of cancer cells and the TME. We also summarized recent advances in targeted lipid metabolism as a radiosensitizer and discussed how these scientific findings could be translated into clinical practice to improve the radiosensitivity of cancer.
Topics: Humans; Lipid Metabolism; Neoplasms; Signal Transduction; Radiation Tolerance; Radiation-Sensitizing Agents; Tumor Microenvironment
PubMed: 37079212
DOI: 10.1007/s12094-023-03134-4 -
Cancer Biology & Therapy Dec 2023As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used...
As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.
Topics: Humans; Radiation Tolerance; Cell Survival; Adenocarcinoma of Lung; Lung Neoplasms; MicroRNAs; Smad3 Protein
PubMed: 36861928
DOI: 10.1080/15384047.2023.2165896 -
Molecular Microbiology Jan 2024Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive.... (Review)
Review
Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive. Desiccation is one of the most common and frequently encountered stresses in nature. On the contrary, ionizing radiations are limited to high local concentrations of naturally occurring radioactive materials and related anthropogenic activities. Yet, resistance to high doses of ionizing radiation is evident across the tree of life. The evolution of desiccation resistance has been linked to the evolution of ionizing radiation resistance, although, evidence to support the idea that the evolution of desiccation tolerance is a necessary precursor to ionizing radiation resistance is lacking. Moreover, the presence of radioresistance in hyperthermophiles suggests multiple paths lead to radiation resistance. In this minireview, we focus on the molecular aspects of damage dynamics and damage response pathways comprising protective and restorative functions with a definitive survival advantage, to explore the serendipitous genesis of ionizing radiation resistance.
Topics: Radiation, Ionizing; Deinococcus; Radiation Tolerance; DNA Repair
PubMed: 38082498
DOI: 10.1111/mmi.15208