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PloS One 2024This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial...
This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former's better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment.
Topics: Radiation Tolerance; Genome, Bacterial; Gamma Rays; Background Radiation; Whole Genome Sequencing; India; Bacillus; DNA Repair
PubMed: 38857267
DOI: 10.1371/journal.pone.0304810 -
Frontiers in Pharmacology 2024Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen...
INTRODUCTION
Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen species (ROS) in prostate cancer cells and . In this study, we tested its anti-cancer spectrum in multiple platforms.
METHODS
We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.
RESULTS
Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.
CONCLUSION
Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index .
PubMed: 38855749
DOI: 10.3389/fphar.2024.1409506 -
BMC Cancer Jun 2024This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina.
MATERIALS AND METHODS
We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion.
RESULTS
A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 Gy (95% CI: 75.3-96.6 Gy).
CONCLUSIONS
A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.
Topics: Humans; Female; Vaginal Neoplasms; Dose-Response Relationship, Radiation; Radiotherapy Dosage; Neoplasm Recurrence, Local; Middle Aged; Treatment Outcome; Aged; Vagina
PubMed: 38851692
DOI: 10.1186/s12885-024-12486-1 -
Radiation Oncology (London, England) Jun 2024Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex...
BACKGROUND
Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study.
METHODS
A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated.
RESULTS
Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants.
CONCLUSION
Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.
Topics: Humans; Prospective Studies; Male; Female; Magnetic Resonance Imaging; Adult; Rotation; Radiotherapy, Image-Guided; Middle Aged; Young Adult; Motion Sickness; Patient Compliance; Anxiety; Healthy Volunteers
PubMed: 38849900
DOI: 10.1186/s13014-024-02461-2 -
Scientific Reports Jun 2024Acclimation to crop niches for thousands of years has made indigenous rice cultivars better suited for stress-prone environments. Still, their response to UV-B...
Acclimation to crop niches for thousands of years has made indigenous rice cultivars better suited for stress-prone environments. Still, their response to UV-B resiliency is unknown. 38 rice landraces were grown in cemented pots in a randomised block design with three replicates under open field conditions in Sambalpur University in the wet season of 2022. Half of the plants in each of the cultivars were administered UV-B radiation at the panicle emergence stage in an adjustable UV-B chamber permitting sunlight, and the effects of the stress on various morpho-physiological features, such as spikelet sterility, flag leaf photosynthetic and flavonoid pigment contents, and lipid peroxidation activities, were estimated for calibration of stress resistance. The experiment identified Swarnaprabha and Lalkain as the most sensitive and resilient to stress respectively, and the differential response between them was further revealed in the expression of genes related to UV-B sensitivity. Subject to the stress, Swarnaprabha exhibited symptoms of injuries, like leaf burns, and a higher loss of various photosynthetic parameters, such as pigment contents, SPAD and Fv/Fm, ETR and qP values, while NPQ increased only in Lalkain. Exposure to UV-B increased the total phenolic and flavonoid contents in Lalkain while depressing them in Swarnaprabha. Such an effect amounted to a higher release of fluorescent energy in the latter. The levels of expression of gene families controlling flavonoid activation and UV-B signal transduction, such as OsWRKY, OsUGT, OsRLCK, OsBZIP, OsGLP, and CPD photolyase were similar in both the cultivars in the control condition. However, exposure to UV-B stress overexpressed them in resilient cultivars only. The magnitude of expression of the genes and the impact of the stress on photosynthetic parameters, phenolic compounds and pubescent hair structure at the panicle emergence stage could be valid indicators among indigenous rice for UV-B tolerance.
Topics: Ultraviolet Rays; Oryza; Photosynthesis; Genetic Variation; Gene Expression Regulation, Plant; Plant Leaves; Flavonoids; Stress, Physiological
PubMed: 38849505
DOI: 10.1038/s41598-024-64134-0 -
Contemporary Clinical Trials... Jun 2024Enteral nutrition (EN) is preferred when oral feeding is not possible. The use of the Nasogastric Tube (NGT) ensures rapid and low-risk nutrient administration. However,...
BACKGROUND
Enteral nutrition (EN) is preferred when oral feeding is not possible. The use of the Nasogastric Tube (NGT) ensures rapid and low-risk nutrient administration. However, confirming the placement through chest radiography, besides delaying the initiation of nutritional therapy, exposes patients to radiation. The pH test of gastric aspirate provides a quicker check for NGT placement, but its reliability is compromised by challenges related to aspirating gastric secretions.
STUDY OBJECTIVE
The main objective of this study is to assess the high-performance placement of NGTs for nutritional purposes, optimizing the evaluation of correct insertion through pH testing using an electronic pH meter. Additionally, the study aims to evaluate patient tolerance to the intervention.
MATERIALS AND METHODS
This single-center RCT will include 150 EN candidate patients divided into three groups. Each group will use distinct NGTs, evaluating placement through pH testing and chest radiography for safety. Tolerance, complications related to NGT placement, and costs will be assessed, with data collected anonymously through a secure electronic database.
ETHICAL CONSIDERATIONS
authorization no. 3624, Territorial Ethical Committee Lombardy 5, October 20, 2023.
IMPLICATIONS AND PERSPECTIVES
This protocol introduces innovative technologies, such as advanced NGTs and an electronic pH meter, aiming to optimize enteral nutrition management. This RCT focuses on replacing X-rays as the primary method for verifying NGT placement, thereby reducing costs, time, and patient exposure to radiation. Data analysis may provide insights into managing patients on pH-altering medication. Implementing innovative technologies has the potential to reduce errors and improve economic efficiency and process sustainability.
PubMed: 38845620
DOI: 10.1016/j.conctc.2024.101312 -
Cell May 2024While ultraviolet (UV) radiation damages DNA, eliciting the DNA damage response (DDR), it also damages RNA, triggering transcriptome-wide ribosomal collisions and...
While ultraviolet (UV) radiation damages DNA, eliciting the DNA damage response (DDR), it also damages RNA, triggering transcriptome-wide ribosomal collisions and eliciting a ribotoxic stress response (RSR). However, the relative contributions, timing, and regulation of these pathways in determining cell fate is unclear. Here we use time-resolved phosphoproteomic, chemical-genetic, single-cell imaging, and biochemical approaches to create a chronological atlas of signaling events activated in cells responding to UV damage. We discover that UV-induced apoptosis is mediated by the RSR kinase ZAK and not through the DDR. We identify two negative-feedback modules that regulate ZAK-mediated apoptosis: (1) GCN2 activation limits ribosomal collisions and attenuates ZAK-mediated RSR and (2) ZAK activity leads to phosphodegron autophosphorylation and its subsequent degradation. These events tune ZAK's activity to collision levels to establish regimes of homeostasis, tolerance, and death, revealing its key role as the cellular sentinel for nucleic acid damage.
PubMed: 38843833
DOI: 10.1016/j.cell.2024.05.018 -
Aging Jun 2024This study explored the role of 14-3-3σ in carbon ion-irradiated pancreatic adenocarcinoma (PAAD) cells and xenografts and clarified the underlying mechanism. The...
This study explored the role of 14-3-3σ in carbon ion-irradiated pancreatic adenocarcinoma (PAAD) cells and xenografts and clarified the underlying mechanism. The clinical significance of 14-3-3σ in patients with PAAD was explored using publicly available databases. 14-3-3σ was silenced or overexpressed and combined with carbon ions to measure cell proliferation, cell cycle, and DNA damage repair. Immunoblotting and immunofluorescence (IF) assays were used to determine the underlying mechanisms of 14-3-3σ toward carbon ion radioresistance. We used the BALB/c mice to evaluate the biological behavior of 14-3-3σ in combination with carbon ions. Bioinformatic analysis revealed that PAAD expressed higher 14-3-3σ than normal pancreatic tissues; its overexpression was related to invasive clinicopathological features and a worse prognosis. Knockdown or overexpression of 14-3-3σ demonstrated that 14-3-3σ promoted the survival of PAAD cells after carbon ion irradiation. And 14-3-3σ was upregulated in PAAD cells during DNA damage (carbon ion irradiation, DNA damaging agent) and promotes cell recovery. We found that 14-3-3σ resulted in carbon ion radioresistance by promoting RPA2 and RAD51 accumulation in the nucleus in PAAD cells, thereby increasing homologous recombination repair (HRR) efficiency. Blocking the HR pathway consistently reduced 14-3-3σ overexpression-induced carbon ion radioresistance in PAAD cells. The enhanced radiosensitivity of 14-3-3σ depletion on carbon ion irradiation was also demonstrated . Altogether, 14-3-3σ functions in tumor progression and can be a potential target for developing biomarkers and treatment strategies for PAAD along with incorporating carbon ion irradiation.
Topics: 14-3-3 Proteins; Pancreatic Neoplasms; Animals; Humans; Mice; Cell Line, Tumor; Recombinational DNA Repair; Mice, Inbred BALB C; Down-Regulation; Radiation Tolerance; Exoribonucleases; Heavy Ion Radiotherapy; Carbon; Cell Proliferation; Gene Expression Regulation, Neoplastic; Male; DNA Damage; Female
PubMed: 38843383
DOI: 10.18632/aging.205896 -
Frontiers in Public Health 2024Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation,...
BACKGROUND
Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR).
METHODS
The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus.
RESULTS
The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group.
CONCLUSION
Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.
Topics: Animals; Gamma Rays; Rats; Cognitive Dysfunction; Male; Hippocampus; Rats, Sprague-Dawley; Dose-Response Relationship, Radiation; Blood-Brain Barrier
PubMed: 38841686
DOI: 10.3389/fpubh.2024.1387330 -
Energy & Environmental Science Jun 2024The technique of alloying FA with Cs is often used to promote structural stabilization of the desirable α-FAPbI phase in halide perovskite devices. However, the precise...
The technique of alloying FA with Cs is often used to promote structural stabilization of the desirable α-FAPbI phase in halide perovskite devices. However, the precise mechanisms by which these alloying approaches improve the optoelectronic quality and enhance the stability have remained elusive. In this study, we advance that understanding by investigating the effect of cationic alloying in CsFAPbI perovskite thin-films and solar-cell devices. Selected-area electron diffraction patterns combined with microwave conductivity measurements reveal that fine Cs tuning (CsFAPbI) leads to a minimization of stacking faults and an increase in the photoconductivity of the perovskite films. Ultra-sensitive external quantum efficiency, kelvin-probe force microscopy and photoluminescence quantum yield measurements demonstrate similar Urbach energy values, comparable surface potential fluctuations and marginal impact on radiative emission yields, respectively, irrespective of Cs content. Despite this, these nanoscopic defects appear to have a detrimental impact on inter-grains'/domains' carrier transport, as evidenced by conductive-atomic force microscopy and corroborated by drastically reduced solar cell performance. Importantly, encapsulated CsFAPbI devices show robust operational stability retaining 85% of the initial steady-state power conversion efficiency for 1400 hours under continuous 1 sun illumination at 35 °C, in open-circuit conditions. Our findings provide nuance to the famous defect tolerance of halide perovskites while providing solid evidence about the detrimental impact of these subtle structural imperfections on the long-term operational stability.
PubMed: 38841317
DOI: 10.1039/d4ee00901k