Differences In Biological Response Research Articles

Inter- and intra-individual differences regarding SARS-CoV-2 and influenza vaccination in pediatric kidney transplant recipients: An observational study.

In kidney transplant recipients (KTRs), viral infection can lead to antibody and/or T-cell mediated rejection, resulting in kidney transplant dysfunction. Therefore, it is critical to prevent infections. However, KTRs exhibit suboptimal responses to SARS-CoV-2 and/or influenza vaccines, partly due to immunosuppressant therapy. Inter- and intra-individual differences in the biological responses to vaccines may also affect patients' antibody production ability. This study included KTRs who received an messenger RNA SARS-CoV-2 vaccine (3 doses), and an inactivated quadrivalent influenza vaccine (1 or 2 doses). We measured the patients' total antibody titers against SARS-CoV-2 spike antigen, and hemagglutination inhibition (HI) titers against influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. Five patients were eligible for this study. Of these 5 KTRs, two produced anti-SARS-CoV-2 spike antibody titers to a seroprotective level, and also produced HI titers against A/H1N1 to a seroprotective level. Another 2 KTRs did not produce seroprotective anti-SARS-CoV-2 antibody titers, but produced seroprotective HI titers against A/H1N1. The remaining KTR produced a seroprotective anti-SARS-CoV-2 antibody titer, but did not produce a seroprotective HI titer against A/H1N1. The 2 KTRs who did not produce seroprotective anti-SARS-CoV-2 antibody titers following vaccination, later developed COVID-19, and this infection increased their titers over the seroprotective level. This study demonstrated that inter- and intra-individual differences in biological responses to vaccines should be considered in pediatric KTRs, in addition to immunosuppressant effects. Personalized regimens, such as augmented or booster doses of vaccines, could potentially improve the vaccination efficacy against SARS-CoV-2 and influenza.

Metabolic, neurotoxic and immunotoxic effects of PFAAs and their mixtures on the proteome of the head kidney and plasma from rainbow trout (Oncorhynchus mykiss)

PFAAs (Perfluoroalkyl acids) are a class of bioaccumulative, persistent and ubiquitous environmental contaminants which primarily occupy the hydrosphere and its sediments. Currently, a paucity of toxicological information exists for short chain PFAAs and complex mixtures. In order to address these knowledge gaps, we performed a 3-week, aqueous exposure of rainbow trout to 3 different concentrations of a PFAA mixture (50, 100 and 500 ng/L) modeled after the composition determined in Lake Ontario. We conducted an additional set of exposures to individual PFAAs (25 nM each of PFOS (12,500 ng/L), PFOA (10,300 ng/L), PFBS (7500 ng/L) or PFBA (5300 ng/L) to evaluate differences in biological response across PFAA congeners. Untargeted proteomics and phosphorylated metabolomics were conducted on the blood plasma and head kidney tissue to evaluate biological response. Plasma proteomic responses to the mixtures revealed several unexpected outcomes including Similar proteomic profiles and biological processes as the PFOS exposure regime while being orders of magnitude lower in concentration and an atypical dose response in terms of the number of significantly altered proteins (FDR < 0.1). Biological pathway analysis revealed the low mixture, medium mixture and PFOS to significantly alter (FDR < 0.05) a number of processes including those involved in lipid metabolism, oxidative stress and the nervous system. We implicate plasma increases in PPARD and PPARG as being directly related to these biological processes as they are known to be important regulators in all 3 processes. In contrast to the blood plasma, the high mixture and PFOA exposure regimes caused the greatest change to the head kidney proteome, altering many proteins being involved in lipid metabolism, oxidative stress and inflammation. Our findings support the pleiotropic effect PFAAs have on aquatic organisms at environmentally relevant doses including those on PPAR signaling, metabolic dysregulation, immunotoxicity and neurotoxicity.

Primary Mouse Aortic Smooth Muscle Cells Exhibit Region- and Sex-Dependent Biological Responses In Vitro.

Despite advancements in elucidating biological mechanisms of cardiovascular remodeling, cardiovascular disease (CVD) remains the leading cause of death worldwide. When stratified by sex, clear differences in CVD prevalence and mortality between males and females emerge. Regional differences in phenotype and biological response of cardiovascular cells are important for localizing the initiation and progression of CVD. Thus, to better understand region and sex differences in CVD presentation, we have focused on characterizing in vitro behaviors of primary vascular smooth muscle cells (VSMCs) from the thoracic and abdominal aorta of male and female mice. VSMC contractility was assessed by traction force microscopy (TFM; single cell) and collagen gel contraction (collective) with and without stimulation by transforming growth factor-beta 1 (TGF-β1) and cell proliferation was assessed by a colorimetric metabolic assay (MTT). Gene expression and TFM analysis revealed region- and sex-dependent behaviors, whereas collagen gel contraction was consistent across sex and aortic region under baseline conditions. Thoracic VSMCs showed a sex-dependent sensitivity to TGF-β1-induced collagen gel contraction (female > male; p = 0.025) and a sex-dependent proliferative response (female > male; p < 0.001) that was not apparent in abdominal VSMCs. Although primary VSMCs exhibit intrinsic region and sex differences in biological responses that may be relevant for CVD presentation, several factors-such as inflammation and sex hormones-were not included in this study. Such factors should be included in future studies of in vitro mechanobiological responses relevant to CVD differences in males and females.

Using meta-analysis to explore the roles of global upwelling exposure and experimental design in bivalve responses to low pH

Low pH conditions, associated with ocean acidification, represent threats to many commercially and ecologically important organisms, including bivalves. However, there are knowledge gaps regarding factors explaining observed differences in biological responses to low pH in laboratory experiments. Specific sources of local adaptation such as upwelling exposure and the role of experimental design, such as carbonate chemistry parameter changes, should be considered. Linking upwelling exposure, as an individual oceanographic phenomenon, to responses measured in laboratory experiments may further our understanding of local adaptation to global change. Here, meta-analysis is used to test the hypotheses that upwelling exposure and experimental design affect outcomes of individual, laboratory-based studies that assess bivalve metabolic (clearance and respiration rate) responses to low pH. Results show that while bivalves generally decrease metabolic activity in response to low pH, upwelling exposure and experimental design can significantly impact outcomes. Bivalves from downwelling or weak upwelling areas decrease metabolic activity in response to low pH, but bivalves from strong upwelling areas increase or do not change metabolic activity in response to low pH. Furthermore, experimental temperature, exposure time and magnitude of the change in carbonate chemistry parameters all significantly affect outcomes. These results suggest that bivalves from strong upwelling areas may be less sensitive to low pH. This furthers our understanding of local adaptation to global change by demonstrating that upwelling alone can explain up to 49 % of the variability associated with bivalve metabolic responses to low pH. Furthermore, when interpreting outcomes of individual, laboratory experiments, scientists should be aware that higher temperatures, shorter exposure times and larger changes in carbonate chemistry parameters may increase the chance of suppressed metabolic activity.

A comparative metabolomics study between grain-sized moxibustion and suspended moxibustion on rats with gastric ulcers

Grain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.

Gender, Racial and Ethnic Differences in Pathologic Response Following Neoadjuvant Chemotherapy for Bladder Cancer Patients

To evaluate trends and racial variations of pathologic complete response (CR) in patients with muscle-invasive bladder cancer undergoing cystectomy. The National Cancer Database was queried for patients with non-metastatic muscle-invasive bladder cancer who underwent neoadjuvant chemotherapy and surgery. The primary endpoints, CR and mortality, were evaluated using the Cochran-Armitage test, multivariable regression, and Kaplan-Meier analyses. The cohort comprised 9955 patients. Non-Hispanic Black (NHB) patients were younger (P < .001), had a higher clinical tumor (P < .001), and had higher clinical node(P = .029) stages at presentation. CR for non-Hispanic White (NHW), NHB, and Hispanic patients were 12.6%, 10.1%, and 11.8%, respectively (P = .030). There was a significant increase in CR trends for NHW patients (P < .001) and increases in NHB (P = .311) and Hispanic patients (P = .236). On multivariable analysis, NHW females had lower odds of achieving CR (odds ratio: 0.83, 95%CI: 0.71-0.97); however, NHB males (hazard ratio: 1.21, 1.01-1.44) and NHB females (hazard ratio: 1.25, 1.03-1.53) had higher overall mortality in adjusted analysis. Survival differences were not observed in patients who achieved CR, regardless of racial background; however, for those with residual disease, the 2-year survival probabilities were 60.7%, 62.5%, and 51.1% for NHW, HW, and NHB patients, respectively (log-rank P = .010). Our findings revealed differences in chemotherapy response based on gender and race or ethnicity. The CR trends for all racial or ethnic groups increased over time. However, Black patients were found to have worse survival, particularly when residual disease was present. Clinical studies with more underrepresented minorities are needed to verify biological differences in response to neoadjuvant chemotherapy.

Metabolomics analysis of dietary restriction results in a longer lifespan due to alters of amino acid levels in larval hemolymph of Bombyx mori

Dietary restriction (DR) has been a very important discovery in modern aging biology research. Its remarkable anti-aging effect has been proved in a variety of organisms, including members of Lepidoptera, but mechanisms by which DR increases longevity are not fully understood. By using the silkworm (Bombyx mori), a model of lepidopteran insect, we established a DR model, isolated hemolymph from fifth instar larvae and employed LC–MS/MS metabolomics to analyze the effect of DR on the endogenous metabolites of silkworm, and tried to clarify the mechanism of DR to prolong lifespan. We identified the potential biomarkers by analyzing the metabolites of the DR and control groups. Then, we constructed relevant metabolic pathways and networks with MetaboAnalyst. DR significantly prolonged the lifespan of silkworm. The differential metabolites between the DR and control groups were mainly organic acids (including amino acid), and amines. These metabolites are involved in metabolic pathways such as amino acid metabolism. Further analysis showed that, the levels of 17 amino acids were significantly changed in the DR group, indicating that the prolonged lifespan was mainly due to changes in amino acid metabolism. Furthermore, we identified 41 and 28 unique differential metabolites in males and females, respectively, demonstrating sex differences in biological responses to DR. The DR group showed higher antioxidant capacity and lower lipid peroxidation and inflammatory precursors, with differences between the sexes. These results provide evidence for various DR anti-aging mechanisms at the metabolic level and novel reference for the future development of DR-simulating drugs or foods.

MP46-05 GENDER, RACIAL AND ETHNIC DIFFERENCES IN PATHOLOGIC RESPONSE FOLLOWING NEOADJUVANT CHEMOTHERAPY FOR BLADDER CANCER PATIENTS

You have accessJournal of UrologyCME1 Apr 2023MP46-05 GENDER, RACIAL AND ETHNIC DIFFERENCES IN PATHOLOGIC RESPONSE FOLLOWING NEOADJUVANT CHEMOTHERAPY FOR BLADDER CANCER PATIENTS Irasema Paster, Jiping Zeng, Alejandro Recio-Boiles, and Juan Chipollini Irasema PasterIrasema Paster More articles by this author , Jiping ZengJiping Zeng More articles by this author , Alejandro Recio-BoilesAlejandro Recio-Boiles More articles by this author , and Juan ChipolliniJuan Chipollini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003292.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The purpose of this study was to evaluate nationwide trends in pathologic complete response (CR) racial variations in patients with muscle-invasive bladder cancer (MIBC) undergoing cystectomy. METHODS: The National Cancer Database was queried for patients from 2004 to 2016 with non-metastatic MIBC who underwent neoadjuvant chemotherapy and definitive surgery. The primary endpoints, CR and mortality, were evaluated using Cochran-Armitage test, multivariable regression, and Kaplan-Meier analyses. RESULTS: The final analytic cohort was 9,955 patients. Non-Hispanic black (NHB) patients presented with younger age (p<0.001), higher comorbidity score (p=0.036), and higher clinical tumor (cT) stage (p<0.001). The overall CR rate was highest for non-Hispanic white (NHW) males (13.4%) while Hispanic white (HW) females and NHB males had lower CR rates (both, 9.1%). There was a significant increase in CR trends for NHW patients (p<0.001), and non-significant increases for NHB (p=0.311) and Hispanic patients (p=0.236). On multivariable analysis, NHW females had significantly lower odds of achieving CR (OR; 0.83, 95%CI 0.71-0.97); however, NHB males (HR: 1.21, 1.01-1.44) and NHB females (HR: 1.25, 1.03-1.53) had higher overall mortality on adjusted analysis. Overall survival differences were not seen in patients who achieved CR regardless of racial background; however, for those with residual disease, the 2-year survival probabilities were 60.7, 62.5, and 51.1% for NHW, HW, and NHB patients, respectively (log-rank p=0.010). CONCLUSIONS: Our findings showed differences in chemotherapy response based on gender and race/ethnicity. The trends in CR for all racial/ethnic groups appear to be increasing over time. However, even after guideline-directed care, black patients were found with worse survival particularly when residual disease is present. Clinical studies with more underrepresented minorities are needed to verify biological differences in response and help mitigate potential socioeconomic disparities in MIBC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e632 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Irasema Paster More articles by this author Jiping Zeng More articles by this author Alejandro Recio-Boiles More articles by this author Juan Chipollini More articles by this author Expand All Advertisement PDF downloadLoading ...

Epigenetics as a Biomarker for Early-Life Environmental Exposure.

There is interest in evaluating the developmental origins of health and disease (DOHaD) which emphasizes the role of prenatal and early-life environments on non-communicable health outcomes throughout the life course. The ability to rigorously assess and identify early-life risk factors for later health outcomes, including those with childhood onset, in large population samples is often limited due to measurement challenges such as impractical costs associated with prospective studies with a long follow-up duration, short half-lives for some environmental toxicants, and lack of biomarkers that capture inter-individual differences in biologic response to external environments. Epigenomic patterns, and DNA methylation in particular, have emerged as a potential objective biomarker to address some of these study design and exposure measurement challenges. In this article, we summarize the literature to date on epigenetic changes associated with specific prenatal and early-life exposure domains as well as exposure mixtures in human observational studies and their biomarker potential. Additionally, we highlight evidence for other types of epigenetic patterns to serve as exposure biomarkers. Evidence strongly supports epigenomic biomarkers of exposure that are detectable across the lifespan and across a range of exposure domains. Current and future areas of research in this field seek to expand these lines of evidence to other environmental exposures, to determine their specificity, and to develop predictive algorithms and methylation scores that can be used to evaluate early-life risk factors for health outcomes across the life span.

623 Variations in in vivo visible light phototesting methodologies

While previously regarded as nonsignificant with minimal to no photobiologic effects, visible light (VL) has now been shown to have biologic effects on skin in subjects with all skin phototypes. However, currently there are no standardized guidelines to perform VL phototesting. A review of the published in vivo VL phototesting methodologies was performed to compare the various phototesting parameters. The methodologies were found to vary at multiple levels including spectral output of the irradiation sources, irradiance level, dosage, single vs. multiple exposures, assessment methods, assessment time points after irradiation, and calculation procedure for VL protection factor (VL-PF) among other variables. Variations in these parameters can cause significant differences in biologic response to VL. Burning and blister formation with VL irradiation reported in some studies, at doses that have been reported to be well tolerated in others, can be attributed to this. The growing interest in VL photobiology warrants careful investigation of the impact of above listed parameters. This in turn will aid in development of a standardized protocol enabling efficient comparisons among studies and establishment of adequate VL-PF.

High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells.

Understanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcriptional profiles of isolated peripheral blood mononuclear cells 8 h after exposure to 1 Gy of X-rays, carbon ions or iron ions with those of non-irradiated cells using microarray technology. All genes that were found differentially expressed in response to either radiation type were up-regulated and predominantly controlled by p53. Quantitative PCR of selected genes revealed a significantly higher up-regulation 24 h after exposure to heavy ions as compared to X-rays, indicating their prolonged activation. This coincided with increased residual DNA damage as evidenced by quantitative γH2AX foci analysis. Furthermore, despite the converging p53 signature between radiation types, specific gene sets related to the immune response were significantly enriched in up-regulated genes following irradiation with heavy ions. In addition, irradiation, and in particular exposure to carbon ions, promoted transcript variation. Differences in basal and iron ion exposure-induced expression of DNA repair genes allowed the identification of a donor with distinct DNA repair profile. This suggests that gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity. In conclusion, we have shown that photon and particle irradiation induce similar transcriptional pathways, albeit with variable amplitude and timing, but also elicit radiation type-specific responses that may have implications for cancer progression and treatment

Different responses of normal cells (red blood cells) and cancer cells (K562 and K562/Dox cells) to low-dose 137Cs gamma-rays.

High-dose radiation is deleterious to cells or tissues. However, the health risks of exposure to low-dose radiation remain unclear. The present study aimed to investigate the biological responses of low-dose gamma-ray in vitro exposure to normal red blood cells (RBCs) and erythroleukemia (K562 and K562/Dox) cancer cells. Cells were given a low dose of 0.03, 0.05 and 0.1 mGy of 137Cs gamma-rays (at a dose rate of 0.001 Gy/min) under in vitro conditions. Cells exposed to 0 Gy served as controls. Hemolysis and reactive oxygen species (ROS) were measured in exposed RBCs following exposure to low-dose gamma-rays. In addition, complete blood count (CBC) parameters were determined in irradiated whole blood. For irradiated K562 and K562/Dox cancer cells, ROS and mitochondrial activity were measured at 0, 30, 60 and 120 post-irradiation times. The results showed no change in the percentage of ROS and hemolysis in irradiated RBCs. The data indicated no perturbation in the CBC parameters in irradiated whole blood. By contrast, statistically significant dose-dependent increases in the percentage of ROS and decreases in the mitochondrial activity in the K562 and K562/Dox cancer cells were observed from 0 min up to 120 min post-irradiation. These findings concluded that there were differences in biological responses in normal cells (RBCs) and cancer cells (K562 and K562/Dox) to low-dose gamma-rays when cells were irradiated under in vitro conditions.

Cognitive disengagement and biological stress responses in early adolescence

Individual differences in biological responses to stress increase risk for the onset and exacerbation of health and psychiatric conditions. Biases in cognitive disengagement are hypothesized to underlie these individual differences in biological responses to stress. However, no studies have examined which cognitive disengagement bias has the strongest relation with biological responses to stress, and no studies have examined this relation during early adolescence, despite evidence that this is a critical developmental window in which patterns of cognition and biological responses to stress influence trajectories of health throughout life. The current study is the first to test whether difficulty disengaging attention versus working memory from valenced stimuli is associated with biological responses to stress in early adolescence. Youth between 11 and 13 years of age completed two computer-based tasks to assess biases in attention and working memory disengagement to valenced stimuli, and then completed a standardized psychosocial stressor. Consistent with expectations, attention and working memory disengagement biases were associated with stress responses of both the neuroendocrine and autonomic nervous systems, but bias valence and cognitive system influenced the directionality of results. These findings inform our understanding of cognitive mechanisms that influence biological stress reactivity.

Comparison of Transcriptomics Changes Induced by TCS and MTCS Exposure in Human Hepatoma HepG2 Cells.

Triclosan (TCS) has been a widely used antibacterial agent in medical and personal care products in the last few decades. Methyl TCS (MTCS) is the major biotransformation product of TCS through replacement of the hydroxyl group with methoxy. Previous studies revealed that MTCS showed reduced toxicity but enhanced environmental persistence, when compared with TCS. Till date, the toxicological molecular mechanisms of TCS and MTCS remain to be clarified. This study aimed to investigate the transcriptomic changes in HepG2 cells induced by TCS and MTCS using microarray chips and to identify key target genes and related signal pathways. The microarray data showed that there were 1664 and 7144 differentially expressed genes (DEGs) in TCS- and MTCS-treated groups, respectively. Gene ontology (GO) enrichment and Kyoto Encyclopedia of genes and genomes (KEGG) analysis revealed that TCS and MTCS induced overlapping as well as distinct transcriptome signatures in HepG2 cells. Both TCS and MTCS could result in various biological responses in HepG2 cells mainly responding to biosynthetic and metabolic processes but probably through different regulatory pathways. Among the selected 50 GO terms, 9 GO terms belonging to the cellular component category were only enriched in the MTCS group, which are mainly participating in the regulation of cellular organelle’s function. KEGG analysis showed that 19 and 59 pathway terms were separately enriched in TCS and MTCS groups, with only seven identical pathways. The selected 10 TCS-specific signal pathways are mainly involved in cell proliferation and apoptosis, while the selected 10 MTCS-specific pathways mainly take part in the regulation of protein synthesis and modification. The overall data suggested that MTCS induced more enriched DEGs, GO terms, and pathway terms than TCS. In conclusion, compared with TCS, MTCS presents lower polarity and stronger lipophilicity, enabling MTCS to cause more extensive transcriptomic changes in HepG2 cells, activate differentiated signal pathways, and finally lead to differences in biological responses.

DNA damage assessment of human breast and lung carcinoma cells irradiated with protons and carbon ions

Differences in biological response of breast and lung cancer cells to 62 MeV/u therapeutic protons and carbon ions are investigated on MCF-7 and HTB177 cells. Hydroxyl radical scavenger, dimethyl s...

DAILY SOCIAL INTERACTIONS AND BIOLOGICAL STRESS REACTIVITY: ARE THERE AGE DIFFERENCES?

Older people experience fewer negative social interactions and report less anger and stress when faced with interpersonal tensions. Little is known, however, about age differences in biological responses to social interactions. We evaluated how salivary DHEA-S, a key indicator of stress reactivity, is associated with daily positive and negative social interactions among midlife and older adults. Participants were drawn from the Daily Health, Stress, and Relationship Study, which includes 93 adults age 40 to 95 who completed 14 days of daily diary interviews and provided saliva samples on four of those days. Multilevel models showed that people had higher DHEA-S on days in which they reported more positive interactions. Older respondents were less reactive to negative interactions relative to younger respondents. These findings indicate that positive social interactions may benefit biological stress reactivity regardless of age, whereas older adults are more resilient to the adverse effects of negative social interactions.

Tuber transcriptome profiling of eight potato cultivars with different cold-induced sweetening responses to cold storage

Tubers are vegetative reproduction organs formed from underground extensions of the plant stem. Potato tubers are harvested and stored for months. Storage under cold temperatures of 2–4 °C is advantageous for supressing sprouting and diseases. However, development of reducing sugars can occur with cold storage through a process called cold-induced sweetening (CIS). CIS is undesirable as it leads to darkened color with fry processing. The purpose of the current study was to find differences in biological responses in eight cultivars with variation in CIS resistance. Transcriptome sequencing was done on tubers before and after cold storage and three approaches were taken for gene expression analysis: 1. Gene expression correlated with end-point glucose after cold storage, 2. Gene expression correlated with increased glucose after cold storage (after-before), and 3. Differential gene expression before and after cold storage. Cultivars with high CIS resistance (low glucose after cold) were found to increase expression of an invertase inhibitor gene and genes involved in DNA replication and repair after cold storage. The cultivars with low CIS resistance (high glucose after cold) showed increased expression of genes involved in abiotic stress response, gene expression, protein turnover and the mitochondria. There was a small number of genes with similar expression patterns for all cultivars including genes involved in cell wall strengthening and phospholipases. It is proposed that the pattern of gene expression is related to chilling-induced DNA damage repair and cold acclimation and that genetic variation in these processes are related to CIS.

Carbon ion and proton beam irradiation of a normal human TK6 lymphoblastoid cell line within a magnetic field of 1.0 tesla.

BackgroundConsidering the increasing simultaneous application of magnetic resonance imaging (MRI) for more precise photon radiotherapy, it will be likely for particle radiotherapy to adopt MRI for future image guiding. It will then be imperative to evaluate the potential biological effects of a magnetic field (MF) on particle irradiation. This study explores such effects on the highly radiosensitive TK6 lymphoblastoid human cell line.MethodsThe following three parameters were measured after irradiation with either carbon ion or proton beams using spread out Bragg peaks and applying different doses within a perpendicular 1.0 T MF: (1) cell survival fraction (14 days postirradiation), (2) treatment-specific apoptosis, which was determined through the measurement of population in the sub-G1 phase, and (3) cell cycle progression by means of flow cytometry. These were compared to the same parameters measured without an MF.ResultsThe clonogenic assay in both treatment groups showed almost identical survival curves with overlapping error bars. The calculated α values with and without an MF were 2.18 (σ=0.245) and 2.17 (σ=0.234) for carbon ions and 1.08 (σ=0.138) and 1.13 (σ=0.0679) for protons, respectively. Similarly, the treatment-specific apoptosis and cell cycle progression showed almost identical curves with overlapping error bars. A two-sample, unpooled t-test analysis was implemented for comparison of all mean values and showed p-values >0.05.ConclusionNo statistically significant difference in biological response of the TK6 cells was observed when they were irradiated using spreadout Bragg peaks within a perpendicular 1.0 T MF as compared to those, which received the same dose without the MF. This should serve as another supporting piece of evidence toward the implementation of MRI in particle radiotherapy, though further research is necessary.

Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells.

Recently, a subpopulation of tumor cells, called cancer stem cells (CSC), has been characterized, and these have emerged as a major topic in cancer research. CSC are proposed to repair DNA damage more efficiently than the rest of tumor cells, resisting chemotherapy or radiotherapy and causing clinical recurrence and metastasis. We aimed to determine the molecular basis of radioresistance and first compared the response to ionizing radiation (IR) between cancer stem cell-enriched cultures grown as spheres and conventional tumor cell line cultures grown as monolayer, from HeLa and MCF-7 cancer cell lines. To verify that our sphere cultures were enriched in CSC, we evaluated the double staining of CD49f and ALDH activity for HeLa cells by flow cytometry. We then evaluated whether differences could exist in sensor elements in the DNA damage response pathway among these cultures. We found that CSC cultures showed less sensitivity to radiation than conventional tumor cell line cultures. We observed a higher baseline expression of activated response sensor proteins of DNA damage, such as ATM, H2A.X, and PARP1, in untreated CSC cultures. These findings provide the first evidence, to our knowledge, that DNA damage response sensor proteins are present and preferentially activated in CSC, as opposed to the bulk of cells in monolayer cultures. Likewise, they provide the basis for biological differences in response to IR between CSC and other tumor cell populations. Understanding the DNA damage response pathway may provide therapeutic targets to sensitize CSC to cytotoxic therapies to improve current cancer treatments.

Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature

AbstractThe therapeutic ratio of radiotherapy is limited by acute or chronic side effects with often severe consequences to patients. The microvasculature is a central player involved in both tumor responses and healthy tissue/organ radiological injuries. However, current preclinical vascular models based on 2D culture offer only limited radiobiological insight due to their failure in recapitulating the 3D nature experienced by endothelial cells within the human microvasculature. To address this issue, the use of a 3D microvasculature‐on‐a‐chip microfluidic technology is demonstrated in radiobiological studies. Within this vasculogenesis model a perfusable network that structurally mimics the human microvasculature is formed and the biological response to ionizing radiation including cellular apoptosis, vessel tight adherens junction breakage, DNA double strand break, and repair is systematically investigated. In comparison to cells grown in a 2D environment, human umbilical vein endothelial cells in the 3D microvasculature‐on‐a‐chip displays significant differences in biological responses, especially at high X‐ray dose. This data confirms the feasibility of using microvascular‐on‐a‐chip models for radiobiological studies. Such vasculogenesis models have strong potential to yield more accurate prediction of healthy tissue responses to ionizing radiation as well as to guide the development of risk‐reducing strategies to prevent radiation‐induced acute and long‐term side‐effects.