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1.
Biophys J ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38902926

ABSTRACT

The gut microbiome affects brain and neuronal development and may contribute to the pathophysiology of neurodevelopmental disorders. However, it is unclear how risk genes associated with such disorders affect gut physiology in a manner that could impact microbial colonization and how the mechanical properties of the gut tissue might play a role in gut-brain bidirectional communication. To address this, we used Drosophila melanogaster with a null mutation in the gene kismet, an ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, these are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found that kismet mutant flies have a significant increase in gastrointestinal transit time, indicating the functional homology of kismet with CHD7/CHD8 in vertebrates. Rheological characterization of dissected gut tissue revealed significant changes in the mechanics of kismet mutant gut elasticity, strain stiffening behavior, and tensile strength. Using 16S rRNA metagenomic sequencing, we also found that kismet mutants have reduced diversity and abundance of gut microbiota at every taxonomic level. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and quantified the flies' courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of the gut microbiome in the control strain reduced courtship activity, demonstrating that antibiotic treatment can have differential impacts on behavior and may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-microbiome-brain axis to influence behavior. We also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neurodevelopment.

2.
BMC Genomics ; 25(1): 710, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39044130

ABSTRACT

BACKGROUND: Identifying the DNA-binding specificities of transcription factors (TF) is central to understanding gene networks that regulate growth and development. Such knowledge is lacking in oomycetes, a microbial eukaryotic lineage within the stramenopile group. Oomycetes include many important plant and animal pathogens such as the potato and tomato blight agent Phytophthora infestans, which is a tractable model for studying life-stage differentiation within the group. RESULTS: Mining of the P. infestans genome identified 197 genes encoding proteins belonging to 22 TF families. Their chromosomal distribution was consistent with family expansions through unequal crossing-over, which were likely ancient since each family had similar sizes in most oomycetes. Most TFs exhibited dynamic changes in RNA levels through the P. infestans life cycle. The DNA-binding preferences of 123 proteins were assayed using protein-binding oligonucleotide microarrays, which succeeded with 73 proteins from 14 families. Binding sites predicted for representatives of the families were validated by electrophoretic mobility shift or chromatin immunoprecipitation assays. Consistent with the substantial evolutionary distance of oomycetes from traditional model organisms, only a subset of the DNA-binding preferences resembled those of human or plant orthologs. Phylogenetic analyses of the TF families within P. infestans often discriminated clades with canonical and novel DNA targets. Paralogs with similar binding preferences frequently had distinct patterns of expression suggestive of functional divergence. TFs were predicted to either drive life stage-specific expression or serve as general activators based on the representation of their binding sites within total or developmentally-regulated promoters. This projection was confirmed for one TF using synthetic and mutated promoters fused to reporter genes in vivo. CONCLUSIONS: We established a large dataset of binding specificities for P. infestans TFs, representing the first in the stramenopile group. This resource provides a basis for understanding transcriptional regulation by linking TFs with their targets, which should help delineate the molecular components of processes such as sporulation and host infection. Our work also yielded insight into TF evolution during the eukaryotic radiation, revealing both functional conservation as well as diversification across kingdoms.


Subject(s)
Evolution, Molecular , Phylogeny , Phytophthora infestans , Transcription Factors , Phytophthora infestans/genetics , Phytophthora infestans/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Binding Sites , Protein Binding
3.
Endoscopy ; 56(10): 780-789, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38641337

ABSTRACT

BACKGROUND: The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting. METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the four treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P score. RESULTS: This network meta-analysis included 3617 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P scores: 0.95 and 0.90, respectively). EUS-GE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P scores for 30-day mortality and reintervention indicated the benefits of PGJ and EUS-GE (cophenetic correlation coefficient: 0.94; PGJ and EUS-GE were in the same cluster). CONCLUSION: PGJ and EUS-GE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or in patients who are unsuitable for EUS-GE.


Subject(s)
Endosonography , Gastric Outlet Obstruction , Gastroenterostomy , Palliative Care , Gastric Outlet Obstruction/etiology , Gastric Outlet Obstruction/surgery , Gastric Outlet Obstruction/therapy , Humans , Palliative Care/methods , Gastroenterostomy/methods , Endosonography/methods , Stents , Network Meta-Analysis , Gastric Bypass/methods , Stomach Neoplasms/complications , Ultrasonography, Interventional
4.
Sensors (Basel) ; 23(8)2023 Apr 11.
Article in English | MEDLINE | ID: mdl-37112238

ABSTRACT

In this study, we consider the combination of clustering and resource allocation based on game theory in ultra-dense networks that consist of multiple macrocells using massive multiple-input multiple-output and a vast number of randomly distributed drones serving as small-cell base stations. In particular, to mitigate the intercell interference, we propose a coalition game for clustering small cells, with the utility function being the ratio of signal to interference. Then, the optimization problem of resource allocation is divided into two subproblems: subchannel allocation and power allocation. We use the Hungarian method, which is efficient for solving binary optimization problems, to assign the subchannels to users in each cluster of small cells. Additionally, a centralized algorithm with low computational complexity and a distributed algorithm based on the Stackelberg game are provided to maximize the network energy efficiency (EE). The numerical results demonstrate that the game-based method outperforms the centralized method in terms of execution time in small cells and is better than traditional clustering in terms of EE.

5.
Ann Surg Oncol ; 29(5): 3038-3049, 2022 May.
Article in English | MEDLINE | ID: mdl-35018590

ABSTRACT

BACKGROUND: Evidence on the accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) for patients with breast cancer is inconclusive. This study reviewed the real-world data to determine the acceptability of SLNB after NAT. METHODS: The study searched for articles in the PubMed, EMBASE, and Cochrane Library databases. The primary outcomes were the identification rate for sentinel lymph nodes (SLNs) and the false-negative rate (FNR) for SLNB. The study also evaluated the FNR in subgroups defined by tumor stage, nodal stage, hormone receptor status, human epidermal growth factor receptor-2 status, tumor response, mapping technique, and number of SLNs removed. RESULTS: The study retrieved 61 prospective and 18 retrospective studies with 10,680 initially cN± patients. The pooled estimate of the identification rate was 0.906 (95 % confidence interval [CI], 0.891-0.922), and the pooled FNR was 0.118 (95 % CI, 0.103-0.133). In subgroup analysis, the FNR was significantly higher for the patients with estrogen receptor (ER)-negative status and fewer than three SLNs removed. The FNR did not differ significantly between the patients with and those without complete tumor response. Among the patients with initial clinical negative axillary lymph nodes, the incidence of node metastasis was 26.8 % (275/1041) after NAT. CONCLUSION: Real-world evidence indicates that the FNR of SLNB after NAT in breast cancer is 11.8 %, exceeding only slightly the commonly adopted threshold of 10 %. The FNR is significantly higher for patients with ER-negative status and removal of fewer than three SLNs. Using a dual tracer and removing at least three SLNs may increase the accuracy of SLNB after NAT.


Subject(s)
Breast Neoplasms , Sentinel Lymph Node , Axilla/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Humans , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoadjuvant Therapy , Prospective Studies , Retrospective Studies , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy/methods
6.
FASEB J ; 35(4): e21398, 2021 04.
Article in English | MEDLINE | ID: mdl-33710675

ABSTRACT

The importance of cell phenotype in determining the molecular mechanisms underlying ß2 -adrenoceptor (ß2AR) function has been noted previously when comparing responses in primary cells and recombinant model cell lines. Here, we have generated haplotype-specific SNAP-tagged ß2AR human embryonic stem (ES) cell lines and applied fluorescence correlation spectroscopy (FCS) to study cell surface receptors in progenitor cells and in differentiated fibroblasts and cardiomyocytes. FCS was able to quantify SNAP-tagged ß2AR number and diffusion in both ES-derived cardiomyocytes and CRISPR/Cas9 genome-edited HEK293T cells, where the expression level was too low to detect using standard confocal microscopy. These studies demonstrate the power of FCS in investigating cell surface ß2ARs at the very low expression levels often seen in endogenously expressing cells. Furthermore, the use of ES cell technology in combination with FCS allowed us to demonstrate that cell surface ß2ARs internalize in response to formoterol-stimulation in ES progenitor cells but not following their differentiation into ES-derived fibroblasts. This indicates that the process of agonist-induced receptor internalization is strongly influenced by cell phenotype and this may have important implications for drug treatment with long-acting ß2AR agonists.


Subject(s)
Embryonic Stem Cells/physiology , Fibroblasts/physiology , Myocytes, Cardiac/physiology , Receptors, Adrenergic, beta-2/metabolism , Spectrometry, Fluorescence/methods , Adrenergic beta-2 Receptor Agonists/pharmacology , Cell Differentiation , Fluorescent Dyes/chemistry , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , HEK293 Cells , Humans , Membrane Proteins , Propranolol/pharmacology , Receptors, Adrenergic, beta-2/chemistry , Receptors, Adrenergic, beta-2/genetics
7.
Am J Obstet Gynecol ; 226(1): 52-67.e10, 2022 01.
Article in English | MEDLINE | ID: mdl-34224687

ABSTRACT

OBJECTIVE: Severe pertussis infection has been reported in infants before receiving routine immunization series. This problem could be solved by vaccinating mothers during pregnancy or children at birth. This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and real-world evidence to evaluate the optimal strategy for pertussis vaccination. DATA SOURCES: PubMed, Embase, and the Cochrane Library databases were searched until December 2020. STUDY ELIGIBILITY CRITERIA: RCTs, cohort studies, case-control studies, and case series were included if they investigated the efficacy, immunogenicity, and safety of acellular pertussis vaccine during pregnancy and at birth. METHODS: Number of pertussis cases, severe adverse events (SAEs), and pertussis antibody concentration in infants before and after they receive routine vaccination series were extracted and random-effect model was used to pool the analyses. RESULTS: Overall, 29 studies were included. Our meta-analysis revealed that pertussis immunization during pregnancy significantly increased the concentrations of 3 pertussis antibodies and reduced the incidence rates of infected infants below 3 months of age (odds ratio, 0.22; 95% confidence interval, 0.14-0.33). Similarly, infants vaccinated at birth had higher levels of pertussis antibody than those who were not. No significant difference in rates of severe adverse events was seen in all vaccination groups (during pregnancy [risk ratio, 1.18; 95% confidence interval, 0.76-1.82] and at birth [risk ratio, 0.72; 95% confidence interval, 0.34-1.54]). CONCLUSION: Pertussis vaccination during pregnancy could protect infants against pertussis disease before the routine vaccination. Pertussis immunization at birth would be an alternative for infants whose mothers did not receive pertussis vaccines during pregnancy.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Mothers , Pertussis Vaccine/administration & dosage , Whooping Cough/prevention & control , Antibody Formation , Child, Preschool , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Female , Humans , Infant , Infant, Newborn , Male , Pertussis Vaccine/adverse effects , Pregnancy , Randomized Controlled Trials as Topic , Vaccination
8.
Future Oncol ; 18(39): 4399-4413, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36786635

ABSTRACT

Aim: This study exploited hepatocellular carcinoma (HCC)-specific circulating DNA methylation profiles to improve the accuracy of a current screening assay for HCC patients in high-risk populations. Methods: Differentially methylated regions in cell-free DNA between 58 nonmetastatic HCC and 121 high-risk patients with liver cirrhosis or chronic hepatitis were identified and used to train machine learning classifiers. Results: The model could distinguish HCC from high-risk non-HCC patients in a validation cohort, with an area under the curve of 0.84. Combining these markers with the three serum biomarkers (AFP, lectin-reactive AFP, des-γ-carboxy prothrombin) in a commercial test, µTASWako®, achieved an area under the curve of 0.87 and sensitivity of 68.8% at 95.8% specificity. Conclusion: HCC-specific circulating DNA methylation markers may be added to the available assay to improve the early detection of HCC.


The early detection of liver cancer in high-risk populations can help people with the disease have a higher chance of survival and better quality of life. However, this is still a healthcare challenge. Current commercial blood tests measuring protein signatures in the blood have low accuracy due to increased levels of these proteins being detected in both liver cancer patients and patients with chronic liver diseases. In this study, we identified a set of signatures in DNA released by cancer cells into the bloodstream and used them as biomarkers to distinguish liver cancer patients from high-risk patients. We also demonstrated that adding those signatures to a commercial blood test currently used in clinics could improve the accuracy in detecting liver cancer patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/pathology , alpha-Fetoproteins/metabolism , DNA Methylation , Biomarkers , Biomarkers, Tumor , Sensitivity and Specificity
9.
Entropy (Basel) ; 24(2)2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35205454

ABSTRACT

This research aims to compare the performance of ARIMA as a linear model with that of the combination of ARIMA and GARCH family models to forecast S&P500 log returns in order to construct algorithmic investment strategies on this index. We used the data collected from Yahoo Finance with daily frequency for the period from 1 January 2000 to 31 December 2019. By using a rolling window approach, we compared ARIMA with the hybrid models to examine whether hybrid ARIMA-SGARCH and ARIMA-EGARCH can really reflect the specific time-series characteristics and have better predictive power than the simple ARIMA model. In order to assess the precision and quality of these models in forecasting, we compared their equity lines, their forecasting error metrics (MAE, MAPE, RMSE, MAPE), and their performance metrics (annualized return compounded, annualized standard deviation, maximum drawdown, information ratio, and adjusted information ratio). The main contribution of this research is to show that the hybrid models outperform ARIMA and the benchmark (Buy&Hold strategy on S&P500 index) over the long term. These results are not sensitive to varying window sizes, the type of distribution, and the type of the GARCH model.

10.
J Pharm Technol ; 38(2): 106-114, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35571348

ABSTRACT

Introduction: Telepharmacy, the application of information and communication technologies in healthcare services, has been adopted in many countries to provide patients with pharmaceutical care. However, it has yet to be widely used in Vietnam. This study was conducted to assess the current status of use and the factors associated with the willingness to use telepharmacy of pharmacists in Vietnam. Methods: A descriptive cross-sectional study was conducted from February to July 2021; 414 pharmacists were recruited to fill in an online survey. Results: Overall, 86.7% of participants have used telepharmacy application and 87.2% of them were willing to apply telepharmacy in pharmacy practice. According to our multivariate analysis, the level of readiness was associated with positive attitude (odds ratio [OR] = 4.67; 95% confidence interval [CI]: 2.26-9.66), and a good behavior (OR = 11.34; 95% CI: 3.84-33.45). Discussion: Developing a telepharmacy system with appropriate features is essential to meet the requirements of pharmacy practice amid the spread of the COVID-19 pandemic.

11.
Fish Shellfish Immunol ; 98: 788-799, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31740400

ABSTRACT

A skin fibroblast cell line WE-skin11f from walleye (Sander vitreus) was used to study the impact of temperature (26 °C, 20 °C, 14 °C, or 4 °C) on the transcript levels of genes involved in the endogenous antigen processing and presentation pathway (EAPP), which is an important antiviral pathway of vertebrates. Partial coding sequences were found for 4 previously unidentified walleye EAPP members, calreticulin, calnexin, erp57, and tapasin, and the constitutive transcript levels of these genes in WE-skin11f was unchanged by culture incubation temperature. The viral mimic poly (I:C) and viral haemorrhagic septicaemia virus (VHSV) IVb were used to study possible induction of EAPP transcripts (b2m, mhIa, and tapasin). The walleye cells were exquisitely sensitive to poly (I:C), losing adherence and viability at concentrations greater than 100 ng/mL, particularly at suboptimal temperatures. VHSV IVb viral particles were produced from infected WE-skin11f cells at 20 °C, 14 °C, and 4 °C but with much lower production at 4 °C. Under conditions where their impact on the viability of WE-skin11f cultures was slight, poly (I:C) and VHSV IVb were shown to induce b2m, mhIa, and tapasin transcript°s at 26 °C and 20 °C respectively. However, at 4 °C, the up-regulation of EAPP transcript levels was either delayed or completely impaired when compared to the 26 °C and 20 °C control temperatures of the respective experiments. These in vitro results suggest that suboptimal temperatures may be capable of modulating the regulation of the EAPP in walleye cells during viral infection.


Subject(s)
Antigen Presentation/genetics , Fish Proteins/immunology , Perches/immunology , Animals , Cell Line , Fibroblasts , Novirhabdovirus/physiology , Perches/genetics , Poly I-C/pharmacology , Temperature , Transcription, Genetic
12.
Environ Res ; 180: 108807, 2020 01.
Article in English | MEDLINE | ID: mdl-31629087

ABSTRACT

Ionizing radiation (IR) is an environmental carcinogen and the biological damages it elicits are mechanistically distinct between high and low doses. Non-targeted effects occurring in nonirradiated cells such as the radiation-induced bystander effect predominate at low doses of IR. However, the role of non-targeted effects in environmental radiation protection is often overlooked because the governing mechanisms are complex and multifactorial. An improved understanding of the signaling molecules and their capacity to sensitize specific cell types are essential in establishing environmental IR risks. In particular, serotonin (5-HT) has been identified to exacerbate both direct irradiation and bystander-induced cell death (CD) in certain cell types, although not all cell types are responsive to 5-HT in this respect. In this study, we further characterize the role of 5-HT and 5-HT receptors (5-HTR) in the amplification of CD following IR exposure in human keratinocytes. We examined the survival of HaCaT cells treated with 5-HT and the 5-HTR antagonists ketanserin (5-HT2A) and ondansetron (5-HT3) following exposure to direct IR and irradiated cell condition medium (ICCM). Nonirradiated cell survival was consistent with the vehicle control among 5-HT concentrations ranging from 0.001 to 100 µM. Significant 5-HT concentration-dependent increases in CD occurred following direct IR exposure. Nonirradiated ICCM-recipient CD was not altered by 5-HT (0.001-100 µM) when present during donor cell irradiation among all IR doses. Increases in direct irradiation CD evoked by 5-HT were significantly attenuated by ondansetron, blocking the effect of 5-HT, whereas ketanserin did not alter CD. Western blotting of these target 5-HTRs revealed protein expression of the 5-HT3 receptor, while the 5-HT2A receptor was not detected. We have demonstrated a definitive role for 5-HT in the exacerbation of CD following direct IR exposure and identified the 5-HT3 receptor as a potential target for ameliorating radiation damage in keratinocytes.


Subject(s)
Bystander Effect , Serotonin , Skin , Cell Death , Humans , Keratinocytes
13.
Environ Res ; 180: 108816, 2020 01.
Article in English | MEDLINE | ID: mdl-31627157

ABSTRACT

The concept of historic radiation doses associated with accidental radioactive releases and their role in leading to radiation-induced non-targeted effects on affected wild animals are currently being evaluated. Previous research studying Fukushima butterfly, Chernobyl bird and fruit fly populations shows that the effects are transgenerational, underlined by the principles of genomic instability, and varied from one species to another. To further expand on the responses of and their sensitivity in different taxonomically distinct groups, the present study sought to reconstruct historic radiation doses and delineate their effects on bank voles (Clethrionomys glareolus) found within a 400-km radius of the Chernobyl Nuclear Power Plant meltdown site. Historic dose reconstruction from the whole-body dose rates for the bank vole samples for their parental generation at the time of radioactive release was performed. Relationships between the historic doses and cytogenetic aberrations and embryonic lethality were examined via graphical presentations. Results suggest that genomic instability develops at the historic dose range of 20-51 mGy while a radioadaptive response develops at the historic dose range of 51-356 mGy. The Linear No-Threshold (LNT) relationship was absent at historic doses of lower than 356 mGy at all generations. However, LNT was apparent when the very high historic dose of 10.28 Gy in one sampling year was factored into the dose response curve for the bank vole generation 21-22. It is worth being reminded that natural mutation accumulation and other environmental stressors outside the realm of dose effects could contribute to the observed effects in a multiple-stressor environment. Nevertheless, the consistent development of genomic instability and radio-adaptive response across generations and sampling sites unearths the utmost fundamental radiobiological principle of transgenerational non-targeted effects. As a result, it calls for better attention and regulation from global governing bodies of environmental health protection.


Subject(s)
Arvicolinae , Chernobyl Nuclear Accident , Radiation Dosage , Animals , Disasters , Nuclear Power Plants
14.
Sensors (Basel) ; 20(19)2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32998406

ABSTRACT

In recent years, deep learning has been successfully used in order to classify partial discharges (PDs) for assessing the condition of insulation systems in different electrical equipment. However, fault diagnosis using deep learning is still challenging, as it requires a large amount of training data, which is difficult and expensive to obtain in the real world. This paper proposes a novel one-shot learning method for fault diagnosis using a small dataset of phase-resolved PDs (PRPDs) in a gas-insulated switchgear (GIS). The proposed method is based on a Siamese network framework, which employs a distance metric function for predicting sample pairs from the same PRPD class or different PRPD classes. Experimental results over the small PRPD dataset that was obtained from an ultra-high-frequency sensor in the GIS show that the proposed method achieves outstanding performance for PRPD fault diagnosis as compared with the previous methods.

15.
Environ Res ; 169: 494-500, 2019 02.
Article in English | MEDLINE | ID: mdl-30530089

ABSTRACT

PURPOSE: To evaluate the development of delayed lethal mutations, the production of medium borne lethal bystander signals, and the acquirement of radiosensitive or radioresistant traits in distant descendant progeny of fish and amphibian cells surviving ionizing radiation MATERIALS AND METHODS: American eel brain endothelial cells (eelB) and African clawed frog epithelial cells (A6) were initially irradiated with gamma rays at 0.5 Gy or 2 Gy. Ionizing radiation (IR)-surviving cells were grown for 27 population doublings (PDs) for eelB and 43 PDs for A6. Reproductive cell death as quantified by clonogenic survival assays was used to determine the development of delayed lethal mutations, the production of medium borne lethal bystander signals, and the acquirement of radiosensitive or radioresistant traits in the progeny survivors. RESULTS: Only medium borne bystander signals produced by 2-Gy-irradiated eelB progeny survivors at 12 PDs could reduce the clonogenic survival of the bystander reporter cells. IR-induced delayed lethal mutations occurred in irradiated eelB cells at 15-18 PDs; however, subsequently propagated progeny cells retained normal replicative abilities. No IR-induced delayed lethal mutations developed in progeny of irradiated A6 cells at up to 43 PDs. eelB progeny survivors did not develop new radiosensitive or radioresistant traits while A6 progeny survivors acquired a new radiosensitive characteristic. CONCLUSION: This study enriches the current literature on the radiobiological characteristics of distant surviving progeny of irradiated fish and amphibian cells and highlights cell-type/species-dependent differential responses to IR. This study is the first to examine the potential transgenerational effects of progenitor irradiation in amphibian cells.


Subject(s)
Dose-Response Relationship, Radiation , Radiation, Ionizing , Amphibians , Animals , Bystander Effect , Endothelial Cells , Gamma Rays
16.
Environ Res ; 170: 383-388, 2019 03.
Article in English | MEDLINE | ID: mdl-30623885

ABSTRACT

PURPOSE: To evaluate if the common field lampricide 3-trifluoromethyl-4-nitrophenol (TFM) that is intended to eradicate the invasive species sea lampreys in the Great Lakes has the potential to sensitize radiation responses in cells from non-targeted native fish MATERIALS AND METHODS: The TFM toxicity was assessed acutely and chronically with the clonogenic fish cell line eelB. The acute toxicity (24-h exposure) was determined by the fluorescent cell viability probe Alamar Blue. The chronic toxicity was determined either by Alamar Blue (7-d exposure) or the clonogenic survival assay (14-d exposure). Pre- and post-exposure of fish cells to environmentally relevant TFM concentrations following gamma irradiation were performed. Clonogenic survival was determined to assess the damage level of radiation-induced reproductive cell death. RESULTS: The chronic toxicity tests were more sensitive than the acute toxicity tests. The 14-d EC50 using the clonogenic survival endpoint was 2.09 ±â€¯0.28 µg/mL and was statistically similar to the 7-d EC50 (1.85 ±â€¯0.07 µg/mL) based on the Alamar Blue-based cytotoxicity endpoint. Post-exposure of cells to environmentally relevant TFM concentrations following irradiation did not have any effect as compared to the irradiation alone group. In contrast, pre-exposure of cells to TFM following irradiation had a negative additive effect when the total radiation dose was 2 Gy, but not 0.1 or 0.5 Gy. CONCLUSION: Our results suggest that the common field lampricide TFM is a potential radiation sensitizer in cells from non-targeted native fish. This could be a health problem of concern for non-targeted native fish if a large accidental radioactive release occurs.


Subject(s)
Nitrophenols/toxicity , Radiation-Sensitizing Agents/toxicity , Animals , Cell Survival , Fishes , Petromyzon/physiology
17.
Environ Res ; 172: 333-337, 2019 05.
Article in English | MEDLINE | ID: mdl-30825683

ABSTRACT

Contrary to the effects of high doses of radiation, the effects of low doses of radiation are still being investigated. Low doses and their non-targeted effects in particular are of special interest for researchers. The accident that occurred at the Chernobyl Nuclear Power Plant (NPP) gives researchers the opportunity to view these effects outside of a laboratory environment. For this paper, the relationship between low historic radiation doses and the persistent genetic damage observed in populations of fruit flies (Drosophila melanogaster) around the Chernobyl NPP over 3 years will be investigated. Data from Zainullin et al. (1992) on the frequency of sex-linked recessive lethals (SLRLs) in D. melanogaster around the Chernobyl NPP. To calculate the absorbed historic external dose, a method based on the Gaussian plume model was used to find the external dose from both plume shine and ground shine. The dose attributed to the ground shine dose made a greater contribution to the overall absorbed external historic radiation dose than the plume shine dose. For earlier generations of Drosophila living in the radioactive contaminated sites, the SLRL frequencies appeared to correlate with the dose in a linear no-threshold relationship. The later descendent generations appeared to have developed a radio-adaptive-like response. This work contributes to the understanding of historic dose effects on wildlife health following the accidental release of high mount of radioactive materials into the environment.


Subject(s)
Chernobyl Nuclear Accident , Drosophila melanogaster , Animals , Drosophila melanogaster/genetics , Drosophila melanogaster/radiation effects , Radiation Dosage , Ukraine
18.
Environ Res ; 168: 230-240, 2019 01.
Article in English | MEDLINE | ID: mdl-30321736

ABSTRACT

Low dose radiation effects have been investigated in Chernobyl for many years but there is uncertainty about initial doses received by many animal species. However, the Fukushima Dai-ichi Nuclear Power Plant accident opens an opportunity to study the effects of the initial low historic dose on directly exposed species and their progeny during a time where the contaminating radionuclides are decaying. In this paper, it is proposed that historic acute exposure and its resulting non-targeted effects (NTEs) may be partially involved in the high mortality/abnormality rates seen across generations of pale grass blue butterflies (Zizeeria maha) around Fukushima. Data from Hiyama et al. (2012) on the morphological abnormality frequencies in Z. maha collected around Fukushima and their progeny were used in this paper. Two dose reconstruction methods based on the Gaussian plume model were used to determine the external absorbed dose to the first exposed generation from both ground shine and plume shine. One method involved the use of the dose rate recorded at the time of collection and only took Cs-137 into account. The other involved using release rates and atmospheric conditions to determine the doses and considered Cs-137 and Cs-134. The reconstructed doses were plotted against the mortality rates and abnormality frequencies across generations. The mortality rates of the progeny from irradiated progenitors increased linearly with the increasing historic radiation doses reconstructed using both Cs-137 and Cs-134 sources. Additionally, a higher level of morphological abnormalities was observed in progeny than in the progenitors. The mean abnormality frequencies also increased throughout generations. As these results are a sign of NTEs being involved, it can be suggested that increasing mutation levels across generations may result, in part, from NTEs induced by the initial low dose received by the first exposed generation. However, continual accumulation of mutations over generations in their natural contaminated habitats remains a likely contributor into the observed outcome.


Subject(s)
Butterflies/radiation effects , Cesium Radioisotopes/metabolism , Fukushima Nuclear Accident , Radiation Monitoring , Animals , Japan , Nuclear Power Plants , Radiation Dosage
19.
J Nanosci Nanotechnol ; 19(2): 1122-1125, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30360214

ABSTRACT

Recently, the graphite based materials have gained interest as excellent platforms to remove aqueous pollutants via adsorption routes. This is given that such materials possess large specific surface area and low density. In the present work, a comparative study of two facile and effective approaches is conventional thermal heating and microwave irradiation methods to fabricate expanded graphite from available flake graphite sources of Vietnam for oil-contaminated water purification. The as-prepared expanded graphite was characterized by using FT-IR, SEM, XRD and BET analysis. The results exhibited that expanded graphite has multilevel pore structures and the surface area of expanded graphite obtained from microwave irradiation and conventional heating was 147.5 (m²/g) and 100.97 (m²/g) under optimal processing conditions. The as-synthesized expanded graphite from the microwave irradiation method was found to have higher adsorption capacities for diesel oil, crude oil, and fuel oil compared to conventional heating method.

20.
J Enzyme Inhib Med Chem ; 34(1): 465-478, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30734614

ABSTRACT

In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Analysis of structure-activity relationships showed that the introduction of different substituents at C-6 position on the quinazolin-4(3H)-4-one moiety, such as 6-chloro or 6-methoxy potentially increased the cytotoxicity of the compounds. In term of caspase activation activity, several compounds were found to exhibit potent effects, (e.g. compounds 7 b, 5n, and 5l). Especially, compound 7 b activated caspases activity by almost 200% in comparison to that of PAC-1. Further docking simulation also revealed that this compound potentially is a potent allosteric inhibitor of procaspase-3.


Subject(s)
Antineoplastic Agents/pharmacology , Caspases/metabolism , Hydrazines/pharmacology , Quinazolines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Hydrazines/chemical synthesis , Hydrazines/chemistry , Molecular Docking Simulation , Molecular Structure , Quinazolines/chemical synthesis , Quinazolines/chemistry , Structure-Activity Relationship
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