RESUMEN
Anthocyanins are the most valuable pigments in Lycium ruthenicum Murray (L. ruthenicum). Although ultraviolet-B (UV-B) irradiation is a key environmental factor influencing anthocyanin biosynthesis in L. ruthenicum, the deep molecular mechanism remains unclear. Herein, we examined the changes in the total anthocyanin content and transcriptomic characteristics of L. ruthenicum leaves following UV-B irradiation treatment. The results showed a twofold increase in anthocyanin content in the leaves of L. ruthenicum after the treatment. The transcriptome analysis showed that the expression of 24 structural genes identified in the anthocyanin synthesis pathway was up-regulated. In particular, F3'H (Unigene0009145) and C4H (Unigene0046607) exhibit notable up-regulation, suggesting their potential roles in anthocyanin synthesis. Protein interaction network results revealed that MYB1 (Unigene0047706) had the highest connectivity, followed by bHLH (Unigene0014085). Additionally, UVR8 (Unigene0067978) and COP1 (Unigene0008780) were found to be highly involved in UV-B signal transduction. These findings provide new insights into the genetic and biochemical mechanisms that regulate anthocyanin production, and could guide agricultural practices to reduce environmental impacts and improve crop yield and quality.
Asunto(s)
Antocianinas , Regulación de la Expresión Génica de las Plantas , Lycium , Hojas de la Planta , Rayos Ultravioleta , Antocianinas/biosíntesis , Lycium/metabolismo , Lycium/genética , Lycium/efectos de la radiación , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Perfilación de la Expresión Génica , Transcriptoma/efectos de la radiación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.
Asunto(s)
Radiación Ionizante , Análisis de la Célula Individual , Transcriptoma , Animales , Ratones , Análisis de la Célula Individual/métodos , Transcriptoma/efectos de la radiación , Células de la Médula Ósea/efectos de la radiación , Células de la Médula Ósea/metabolismo , Ratones Endogámicos C57BL , Tolerancia a Radiación/genética , Perfilación de la Expresión Génica , Células Madre Hematopoyéticas/efectos de la radiación , Células Madre Hematopoyéticas/metabolismo , Neutrófilos/efectos de la radiación , Neutrófilos/metabolismoRESUMEN
Light quality has significant effects on the growth and metabolite accumulation of algal cells. However, the related mechanism has not been fully elucidated. This study reveals that both red and blue light can promote the growth and biomass accumulation of Chlorella pyrenoidosa, with the enhancing effect of blue light being more pronounced. Cultivation under blue light reduced the content of total carbohydrate in Chlorella pyrenoidosa, while increasing the content of protein and lipid. Conversely, red light decreased the content of protein and increased the content of carbohydrate and lipid. Blue light induces a shift in carbon flux from carbohydrate to protein, while red light transfers carbon flux from protein to lipid. Transcriptomic and metabolomic analysis indicated that both red and blue light positively regulate lipid synthesis in Chlorella pyrenoidosa, but they exhibited distinct impacts on the fatty acid compositions. These findings suggest that manipulating light qualities can modulate carbon metabolic pathways, potentially converting protein into lipid in Chlorella pyrenoidosa.
Asunto(s)
Chlorella , Luz , Lípidos , Metabolómica , Chlorella/metabolismo , Chlorella/efectos de la radiación , Chlorella/crecimiento & desarrollo , Chlorella/genética , Lípidos/biosíntesis , Transcriptoma/efectos de la radiación , Metabolismo de los Lípidos/efectos de la radiación , Ácidos Grasos/metabolismo , Ácidos Grasos/biosíntesis , BiomasaRESUMEN
Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal-to-human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Unirradiated mice were treated with vehicle or 50, 100, or 200 mg/kg BIO 300, and irradiated mice were treated with 200 mg/kg or BIO 300 or vehicle prior to TBI. Whole-blood samples were collected after the last dose of the drug and after irradiation. RNA sequencing demonstrated 100 and 200 mg/kg of BIO 300 doses caused significantly more differential gene expression at 48 h after drug dose compared to 50 mg/kg of BIO 300 (7648, 7680, and 55 significantly differently expressed genes, respectively). Interestingly, following TBI, there were no significantly differentially expressed genes between vehicle- and BIO 300-treated mice. Despite the lack of significant changes in gene expression, the transcriptomic profiles in both groups indicated differential changes in signaling pathways. Pathway analysis of the transcriptome profile from vehicle-treated/TBI mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.
Asunto(s)
Transcriptoma , Irradiación Corporal Total , Animales , Ratones , Transcriptoma/efectos de la radiación , Transcriptoma/efectos de los fármacos , Masculino , Protectores contra Radiación/farmacología , Perfilación de la Expresión Génica/métodos , Biomarcadores/sangre , Regulación de la Expresión Génica/efectos de la radiación , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
BACKGROUND: Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging. OBJECTIVE: Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation. METHODS: iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12â¯h after irradiation with 30 or 150â¯J/m2 of UV-B using microarray analysis. RESULTS: XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150â¯J/m2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30â¯J/m2 UV exposure. CONCLUSION: We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.
Asunto(s)
Diferenciación Celular , Reparación del ADN , Células Madre Pluripotentes Inducidas , Melanocitos , Rayos Ultravioleta , Xerodermia Pigmentosa , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Melanocitos/efectos de la radiación , Melanocitos/metabolismo , Xerodermia Pigmentosa/genética , Xerodermia Pigmentosa/metabolismo , Xerodermia Pigmentosa/patología , Diferenciación Celular/efectos de la radiación , Reparación del ADN/efectos de la radiación , Perfilación de la Expresión Génica , Células Cultivadas , Melaninas/biosíntesis , Melaninas/metabolismo , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Proteína de la Xerodermia Pigmentosa del Grupo A/metabolismo , Transcriptoma/efectos de la radiaciónRESUMEN
BACKGROUND: Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling. METHODS: Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis. RESULTS: Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified. CONCLUSION: Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.
Asunto(s)
Fotones , Neoplasias de la Próstata , Receptores Androgénicos , Transducción de Señal , Transcriptoma , Proteína p53 Supresora de Tumor , Humanos , Masculino , Carbono , Línea Celular Tumoral , Daño del ADN/efectos de la radiación , Reparación del ADN , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Radioterapia de Iones Pesados , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Transducción de Señal/efectos de la radiación , Transcriptoma/efectos de la radiación , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The dose effect of radiation has long been a topic of concern, but the molecular mechanism behind it is still unclear. In this study, dried pea seeds were irradiated with 252Cf fission neutron source. Through analyzing the transcriptome and proteome of M1 generation pea (Pisum sativum L.) leaves, we studied the molecular rule and mechanism of neutron dose effect. Our results showed three important rules of global gene expression in the studied dose range. The rule closely related to the neutron absorbed dose at the transcription and translation levels is: the greater the difference in neutron absorbed dose between two radiation treatment groups, the greater the difference in differential expression between the two groups and the control group. We also obtained important sensitive metabolic pathways of neutron radiation, as well as related key genes. Furthermore, the overall molecular regulation mechanism of dose effect was revealed based on the main functional items obtained. Our research results can be applied to appropriate radiation dose estimation and agricultural production practice.
Asunto(s)
Neutrones , Pisum sativum , Pisum sativum/efectos de la radiación , Pisum sativum/genética , Relación Dosis-Respuesta en la Radiación , Transcriptoma/efectos de la radiación , Dosis de Radiación , Hojas de la Planta/efectos de la radiación , Hojas de la Planta/metabolismo , Semillas/efectos de la radiación , Proteoma/efectos de la radiación , Proteoma/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de la radiaciónRESUMEN
Radiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications.
Asunto(s)
Lesión Pulmonar , Análisis de la Célula Individual , Animales , Ratas , Lesión Pulmonar/etiología , Lesión Pulmonar/genética , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Análisis de la Célula Individual/métodos , Transcriptoma/efectos de la radiación , Pulmón/patología , Pulmón/efectos de la radiación , Pulmón/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/genética , Perfilación de la Expresión Génica/métodos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de la radiación , Miocitos del Músculo Liso/patología , Masculino , Traumatismos por Radiación/patología , Traumatismos por Radiación/genética , Traumatismos por Radiación/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de la radiación , Ratas Sprague-DawleyRESUMEN
PURPOSE: To identify sensitive genes for space radiation, we integrated the transcriptomic samples of spaceflight mice from GeneLab and predicted the radiation doses absorbed by individuals in space. METHODS AND MATERIALS: A single-sample network (SSN) for each individual sample was constructed. Then, using machine learning and genetic algorithms, we built the regression models to predict the absorbed dose equivalent based on the topological structure of SSNs. Moreover, we analyzed the SSNs from each tissue and compared the similarities and differences among them. RESULTS: Our model exhibited excellent performance with the following metrics: R2=0.980, MSE=6.74e-04, and the Pearson correlation coefficient of 0.990 (p value <.0001) between predicted and actual values. We identified 20 key genes, the majority of which had been proven to be associated with radiation. However, we uniquely established them as space radiation sensitive genes for the first time. Through further analysis of the SSNs, we discovered that the different tissues exhibited distinct mechanisms in response to space stressors. CONCLUSIONS: The topology structures of SSNs effectively predicted radiation doses under spaceflight conditions, and the SSNs revealed the gene regulatory patterns within the organisms under space stressors.
Asunto(s)
Radiación Cósmica , Vuelo Espacial , Animales , Ratones , Radiación Cósmica/efectos adversos , Dosis de Radiación , Relación Dosis-Respuesta en la Radiación , Aprendizaje Automático , Redes Reguladoras de Genes/efectos de la radiación , Transcriptoma/efectos de la radiaciónRESUMEN
PURPOSE: People are exposed to low-dose radiation in medical diagnosis, occupational, or life circumstances, but the effect of low-dose radiation on human health is still controversial. The biological effects of radiation below 100 mGy are still unproven. In this study, we observed the effects of low-dose radiation (100 mGy) on gene expression in human coronary artery endothelial cells (HCAECs) and its effect on molecular signaling. MATERIALS AND METHODS: HCAECs were exposed to 100 mGy ionizing radiation at 6 mGy/h (low-dose-rate) or 288 mGy/h (high-dose-rate). After 72 h, total RNA was extracted from sham or irradiated cells for Quant-Seq 3'mRNA-Seq, and bioinformatic analyses were performed using Metascape. Gene profiling was validated using qPCR. RESULTS: Compared to the non-irradiated control group, 100 mGy of ionizing radiation at 6 mGy/h altered the expression of 194 genes involved in signaling pathways related to heart contraction, blood circulation, and cardiac myofibril assembly differentially. However, 100 mGy at 288 mGy/h altered expression of 450 genes involved in cell cycle-related signaling pathways, including cell division, nuclear division, and mitosis differentially. Additionally, gene signatures responding to low-dose radiation, including radiation dose-specific gene profiles (HIST1H2AI, RAVER1, and POTEI) and dose-rate-specific gene profiles (MYL2 for the low-dose-rate and DHRS9 and CA14 for the high-dose-rate) were also identified. CONCLUSIONS: We demonstrated that 100 mGy low-dose radiation could alter gene expression and molecular signaling pathways at the low-dose-rate and the high-dose-rate differently. Our findings provide evidence for further research on the potential impact of low-dose radiation on cardiovascular function.
Asunto(s)
Biología Computacional , Vasos Coronarios , Relación Dosis-Respuesta en la Radiación , Células Endoteliales , Transcriptoma , Humanos , Vasos Coronarios/efectos de la radiación , Vasos Coronarios/citología , Células Endoteliales/efectos de la radiación , Células Endoteliales/metabolismo , Transcriptoma/efectos de la radiación , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de la radiación , Dosis de Radiación , Transducción de Señal/efectos de la radiaciónRESUMEN
Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm2) emitted by a UV-R tanning device. At 96 h post-exposure, 5 mJ/cm2 induced 116 statistically significant differentially expressed genes (DEGs) associated with structural changes from UV-R damage. The highest number of significant gene expression changes occurred at 6 and 48 h post-exposure in the 20 and 40 mJ/cm2 dose groups. Notably, at 40 mJ/cm2, 13 DEGs related to skin barrier homeostasis were consistently perturbed across all timepoints. UV-R exposure activated pathways involving oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance, and innate immunity. This in vivo study's transcriptional data offers mechanistic insights into both short-term and potential non-threshold-dependent long-term health effects of UV-R tanning.
Asunto(s)
Perfilación de la Expresión Génica , Ratones Endogámicos C57BL , Piel , Rayos Ultravioleta , Animales , Rayos Ultravioleta/efectos adversos , Ratones , Piel/efectos de la radiación , Piel/metabolismo , Transcriptoma/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , FemeninoRESUMEN
It aimed to investigate the mechanism of magnetic nanoparticles (MNPs) on atrial fibrillation and effect of n-isopropyl acrylamide coated MNPs (NIPA-co-MN) on the treatment of atrial fibrillation. Ten beagles weighing 20 - 25 kg were randomly divided into test group and control group. Dogs with atrial fibrillation were set as test group, and non-atrial fibrillation dogs as control group. The expression of long non-coding RNA (lncRNA) differentially expressed in the right anterior adipose pad in atrial fibrillation and non-atrial fibrillation dogs was detected by high-throughput sequencing. The relationship between lncRNA and cardiac autonomic nerve remodeling (CANR) was explored. In addition, 20 beagles weighing 20-25 kg were selected to study the therapeutic effect of n-isopropylacrylamide magnetic nanoparticles (NIPA-co-MN) on atrial fibrillation, and statistical analysis was performed. The volume and number of new neurons in the anterior right fat pad of atrium of test group were larger than the control group. The test group dogs produced 45 brand-new lncRNA, including 15 up-regulated transcripts and 30 down-regulated transcripts. MNPs injection can slow down the reduction of ventricular rate in right inferior ganglion plexus. The anterior right ganglion plexus resulted in a reduced amplitude of sinus tachyarrhythmia. This study provided references for the discovery of new diagnostic biomarkers or therapeutic targets and for the treatment of patients with atrial fibrillation.
Asunto(s)
Fibrilación Atrial/cirugía , Vías Autónomas , Ablación por Catéter , Nanopartículas de Magnetita , ARN Largo no Codificante , Acrilamidas/química , Animales , Vías Autónomas/efectos de los fármacos , Vías Autónomas/efectos de la radiación , Modelos Animales de Enfermedad , Perros , Atrios Cardíacos/inervación , Atrios Cardíacos/cirugía , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Análisis de Secuencia de ARN , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Transcriptoma/efectos de la radiaciónRESUMEN
Development of an efficient liquid fermentation method is helpful for food and pharmaceutical applications. This study investigated the effect of ultrasonication on the liquid fermentation of Ganoderma lucidum, a popular edible and medical fungi. Significant changes at both metabolic and transcriptional levels in mycelia were induced by ultrasound treatment. Compared with the control, 857 differential metabolites were identified (578 up- and 279 down-regulated metabolites), with more metabolites biosynthesis after sonication; 569 differentially expressed genes (DEGs) (267 up- and 302 down-) and 932 DEGs (378 up- and 554 down-) were identified in ultrasound-treated samples with recovery time of 0.5 and 3 h, respectively. Furthermore, 334 DEGs were continuously induced within the recovery time of 3 h, indicating the lasting influence of sonication on mycelia. The DEGs and differential metabolites were mainly involved in pathways of carbohydrate, energy metabolism, amino acids, terpenoids biosynthesis and metabolism and membrane transport, suggesting that ultrasound induced multifaceted effects on primary and secondary metabolism. Ultrasonication enhanced the triterpenoids production of G. lucidum (34.96 %) by up-regulating the expression of terpenoids synthase genes. This study shows that the application of ultrasound in liquid fermentation of G. lucidum is an efficient approach to produce more metabolites.
Asunto(s)
Fermentación , Reishi , Ultrasonido , Fermentación/efectos de la radiación , Metaboloma/efectos de la radiación , Reishi/metabolismo , Transcriptoma/efectos de la radiaciónRESUMEN
Metastasis is the leading cause of cancer patient death, which is closely correlated with reactive oxygen species (ROS) levels. It is well known that the effects of ROS on tumors are diverse, depending on ROS concentration and cell type. We found that ovarian cancer cells have significantly lower levels of ROS than normal ovarian cells. Moreover, increased ROS levels in ovarian cancer cells can substantially inhibit their migration and invasion ability. Furthermore, the results show that moderate static magnetic field (SMF) can inhibit ovarian cancer cell migration, invasion, and stemness in a ROS-dependent manner. RNA sequencing results confirm that SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells. Consistently, the expressions of stemness-related genes were significantly decreased, including hyaluronan receptor (CD44), SRY-box transcription factor 2 (Sox2), and cell myc proto-oncogene protein (C-myc). Furthermore, moderate SMFs provided by a superconducting magnet and permanent magnet have good biosafety and can both inhibit ovarian cancer metastasis in mice. Therefore, our study demonstrates the effects of SMFs on oxidative stress and metastasis in the ovarian cancer cells, which reveals the potential of applying SMF as a physical method in cancer therapy in the future.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Magnetoterapia/métodos , Neoplasias Ováricas/radioterapia , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Transcriptoma/efectos de la radiación , Animales , Apoptosis , Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Rapeseed (Brassica napus) is one of the major important oil crops worldwide and is largely cultivated in the Qinghai-Tibetan plateau (QTP), where long and strong solar-radiation is well-known. However, the molecular mechanisms underlying rapeseed's response to light stress are largely unknown. In the present study, the color of rapeseed seedlings changed from green to purple under high light (HL) stress conditions. Therefore, changes in anthocyanin metabolism and the transcriptome of rapeseed seedlings cultured under normal light (NL) and HL conditions were analyzed to dissect how rapeseed responds to HL at the molecular level. Results indicated that the contents of anthocyanins, especially glucosides of cyanidin, delphinidin, and petunidin, which were determined by liquid chromatography-mass spectrometry (LC-MS), increased by 9.6-, 4.2-, and 59.7-fold in rapeseed seedlings exposed to HL conditions, respectively. Next, RNA-sequencing analysis identified 7390 differentially expressed genes (DEGs), which included 4393 up-regulated and 2997 down-regulated genes. Among the up-regulated genes, many genes related to the anthocyanin-biosynthetic pathway were enriched. For example, genes encoding dihydroflavonol reductase (BnDFR) and anthocyanin synthase (BnANS) were especially induced by HL conditions, which was also confirmed by RT-qPCR analysis. In addition, two PRODUCTION OF ANTHOCYANIN PIGMENTATION 2 (BnPAP2) and GLABRA3 (BnGL3) genes encoding MYB-type and bHLH-type transcription factors, respectively, whose expression was also up-regulated by HL stress, were found to be associated with the changes in anthocyanin biosynthesis. Many genes involved in the jasmonic acid (JA)-biosynthetic pathway were also up-regulated under HL conditions. This finding, which is in agreement with the well-known positive regulatory role of JA in anthocyanin biosynthesis, suggests that the JA may also play a key role in the responses of rapeseed seedlings to HL. Collectively, these data indicate that anthocyanin biosynthesis-related and JA biosynthesis-related pathways mediate HL responses in rapeseed. These findings collectively provide mechanistic insights into the mechanisms involved in the response of rapeseed to HL stress, and the identified key genes may potentially be used to improve HL tolerance of rapeseed cultivars through genetic engineering or breeding strategies.
Asunto(s)
Antocianinas/biosíntesis , Vías Biosintéticas/genética , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Transcriptoma/efectos de la radiación , Antocianinas/análisis , Brassica napus/química , Brassica napus/crecimiento & desarrollo , Brassica napus/metabolismo , Ciclopentanos/análisis , Luz , Oxilipinas/análisis , Pigmentación/genética , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN de Planta/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
Centella asiatica is rich in medical and cosmetic properties. While physiological responses of C. asiatica to light have been widely reported, the knowledge of the effects of light on its gene expression is sparse. In this study, we used RNA sequencing (RNA-seq) to investigate the expression of the C. asiatica genes in response to monochromatic red and blue light. Most of the differentially expressed genes (DEGs) under blue light were up-regulated but those under red light were down-regulated. The DEGs encoded for CRY-DASH and UVR3 were among up-regulated genes that play significant roles in responses under blue light. The DEGs involved in the response to photosystem II photodamages and in the biosynthesis of photoprotective xanthophylls were also up-regulated. The expression of flavonoid biosynthetic DEGs under blue light was up-regulated but that under red light was down-regulated. Correspondingly, total flavonoid content under blue light was higher than that under red light. The ABI5, MYB4, and HYH transcription factors appeared as hub nodes in the protein-protein interaction network of the DEGs under blue light while ERF38 was a hub node among the DEGs under red light. In summary, stress-responsive genes were predominantly up-regulated under blue light to respond to stresses that could be induced under high energy light. The information obtained from this study can be useful to better understand the responses of C. asiatica to different light qualities.
Asunto(s)
Centella/genética , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Transcriptoma/efectos de la radiación , Centella/efectos de la radiación , Genes de Plantas/efectos de la radiación , Luz , Estrés Fisiológico/efectos de la radiaciónRESUMEN
Radiotherapy (RT) is an effective treatment option for cancer; however, its efficacy remains less than optimal in locally advanced cancer. Immune checkpoint inhibitor-based therapy, including the administration of anti-PD-L1 antibodies, is a promising approach that works synergistically with RT. Proton beam therapy and carbon-ion therapy are common options for patients with cancer. Proton and carbon ions are reported to induce an immune reaction in cancer cells; however, the underlying mechanisms remain unclear. Here, we aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 6-24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis.
Asunto(s)
Carbono , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Inmunidad/efectos de la radiación , Protones , Transcriptoma/efectos de la radiación , Rayos X , Línea Celular Tumoral , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/inmunología , Ontología de Genes , Humanos , Inmunidad/genética , Iones , RNA-Seq/métodos , Radiación/clasificación , Transducción de Señal/genética , Transducción de Señal/inmunología , Transducción de Señal/efectos de la radiación , Transcriptoma/inmunologíaRESUMEN
Black net shade treatment attenuates flavonoid biosynthesis in tea plants, while the effect of light quality is still unclear. We investigated the flavonoid and transcriptome profiles of tea leaves under different light conditions, using black nets with different shade percentages, blue, yellow and red nets to alter the light intensity and light spectral composition in the fields. Flavonol glycosides are more sensitive to light intensity than catechins, with a reduction percentage of total flavonol glycosides up to 79.6% compared with 38.7% of total catechins under shade treatment. A total of 29,292 unigenes were identified, and the KEGG result indicated that flavonoid biosynthesis was regulated by both light intensity and light spectral composition while phytohormone signal transduction was modulated under blue net shade treatment. PAL, CHS, and F3H were transcriptionally downregulated with light intensity. Co-expression analysis showed the expressions of key transcription factors MYB12, MYB86, C1, MYB4, KTN80.4, and light signal perception and signaling genes (UVR8, HY5) had correlations with the contents of certain flavonoids (p < 0.05). The level of abscisic acid in tea leaves was elevated under shade treatment, with a negative correlation with TFG content (p < 0.05). This work provides a potential route of changing light intensity and spectral composition in the field to alter the compositions of flavor substances in tea leaves and regulate plant growth, which is instructive to the production of summer/autumn tea and matcha.
Asunto(s)
Camellia sinensis/genética , Flavonoides/biosíntesis , Redes Reguladoras de Genes , Luz , Hojas de la Planta/genética , Proteínas de Plantas/genética , Transcriptoma/efectos de la radiación , Camellia sinensis/química , Camellia sinensis/crecimiento & desarrollo , Camellia sinensis/efectos de la radiación , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/química , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/efectos de la radiación , Proteínas de Plantas/metabolismoRESUMEN
The germicidal properties of short wavelength ultraviolet C (UVC) light are well established and used to inactivate many viruses and other microbes. However, much less is known about germicidal effects of terrestrial solar UV light, confined exclusively to wavelengths in the UVA and UVB regions. Here, we have explored the sensitivity of the human coronaviruses HCoV-NL63 and SARS-CoV-2 to solar-simulated full spectrum ultraviolet light (sUV) delivered at environmentally relevant doses. First, HCoV-NL63 coronavirus inactivation by sUV-exposure was confirmed employing (i) viral plaque assays, (ii) RT-qPCR detection of viral genome replication, and (iii) infection-induced stress response gene expression array analysis. Next, a detailed dose-response relationship of SARS-CoV-2 coronavirus inactivation by sUV was elucidated, suggesting a half maximal suppression of viral infectivity at low sUV doses. Likewise, extended sUV exposure of SARS-CoV-2 blocked cellular infection as revealed by plaque assay and stress response gene expression array analysis. Moreover, comparative (HCoV-NL63 versus SARS-CoV-2) single gene expression analysis by RT-qPCR confirmed that sUV exposure blocks coronavirus-induced redox, inflammatory, and proteotoxic stress responses. Based on our findings, we estimate that solar ground level full spectrum UV light impairs coronavirus infectivity at environmentally relevant doses. Given the urgency and global scale of the unfolding SARS-CoV-2 pandemic, these prototype data suggest feasibility of solar UV-induced viral inactivation, an observation deserving further molecular exploration in more relevant exposure models.
Asunto(s)
Infecciones por Coronavirus/prevención & control , Coronavirus Humano NL63/efectos de la radiación , Infecciones del Sistema Respiratorio/prevención & control , SARS-CoV-2/efectos de la radiación , Luz Solar , Rayos Ultravioleta , Animales , Línea Celular , Chlorocebus aethiops , Coronavirus Humano NL63/fisiología , Células Epiteliales/virología , Genoma Viral/efectos de la radiación , Humanos , SARS-CoV-2/fisiología , Transcriptoma/efectos de la radiación , Ensayo de Placa Viral , Inactivación de Virus/efectos de la radiación , Replicación Viral/efectos de la radiaciónRESUMEN
C4 plants frequently experience high light and high temperature conditions in the field, which reduce growth and yield. However, the mechanisms underlying these stress responses in C4 plants have been under-explored, especially the coordination between mesophyll (M) and bundle sheath (BS) cells. We investigated how the C4 model plant Setaria viridis responded to a four-hour high light or high temperature treatment at photosynthetic, transcriptomic, and ultrastructural levels. Although we observed a comparable reduction of photosynthetic efficiency in high light or high temperature treated leaves, detailed analysis of multi-level responses revealed important differences in key pathways and M/BS specificity responding to high light and high temperature. We provide a systematic analysis of high light and high temperature responses in S. viridis, reveal different acclimation strategies to these two stresses in C4 plants, discover unique light/temperature responses in C4 plants in comparison to C3 plants, and identify potential targets to improve abiotic stress tolerance in C4 crops.