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Skin wounds heal faster during stem cell differentiation. Cold plasma reportedly enhances cell proliferation and differentiation and enhances the efficacy of stem cell therapy. However, the exact mechanism of action involved remains unknown. Therefore, this study aimed to evaluate the effect of a combination therapy involving the transplantation of mouse mesenchymal stem cells (mMSCs) into mice with wounds followed by their activation using no-ozone cold plasma (NCP). Balb/c mMSCs were transplanted into BALB/c mice and treated with NCP for 5 min. The animals were divided into four groups based on treatments received: no treatment (Wound), mMSCs only (mMSC), NCP only (NCP), and both mMSC and NCP (mMSC + NCP). NCP treatment was administered six times over two weeks, and tissue samples were prepared by sacrificing the mice in the 1st and 2nd weeks. The wound healing efficacy was assessed using morphological, histological, and molecular approaches including wound healing length measurements, hematoxylin and eosin staining, Masson trichrome staining, immunofluorescence staining, immunohistochemistry, and real-time polymerase chain reaction. The wound healing effect was better in the mMSC + NCP group than that in the groups treated with either. Tracking the injected mMSCs in mice also revealed that the mMSC + NCP group had a greater survival rate. Furthermore, upon wound healing, the mMSC + NCP group exhibited elevated levels of growth factors, like platelet-derived growth factor, transforming growth factor-beta, and vascular endothelial growth factor. These results suggest that NCP stimulated transplanted mMSCs, resulting in faster wound healing. Therefore, further studies are warranted in preclinical and clinical studies to confirm this effect.
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PURPOSE: Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging. PROCEDURES: In this study, 5xFAD mice were used as the animal model. At the age of 5 months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2 months at a dose of 1 mg·kg-1·day-1. At 7 months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans. RESULTS: The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7-8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage. CONCLUSIONS: The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD.
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BACKGROUND: DNA methylation forms 5-methylcytosine and its regulation in the hippocampus is critical for learning and memory. Indeed, dysregulation of DNA methylation is associated with neurological diseases. Alzheimer's disease (AD) is the predominant of dementia and a neurodegenerative disorder. METHODS: We examined the learning and memory function in 3- and 9-month-old wild-type and 5xfamiliar Alzheimer's disease (5xFAD) transgenic mice by performing the object recognition memory and Y-maze tests, and identified the hippocampal amyloid beta burden. To investigate the epigenetically regulated genes involved in the development or neuropathology of AD, we performed genome-wide DNA methylation sequencing and RNA sequencing analyses in the hippocampus of 9-month-old wild-type and 5xFAD tg mice. To validate the genes inversely regulated by epigenetics, we confirmed their methylation status and mRNA levels. RESULTS: At 9 months of age, 5xFAD tg mice showed significant cognitive impairment and amyloid-beta plaques in the hippocampus. DNA methylation sequencing identified a total of 13,777 differentially methylated regions, including 4484 of hyper- and 9293 of hypomethylated regions, that are associated with several gene ontology (GO) terms including 'nervous system development' and 'axon guidance'. In RNA sequencing analysis, we confirmed a total of 101 differentially expressed genes, including 52 up- and 49 downregulated genes, associated with GO functions such as 'positive regulation of synaptic transmission, glutamatergic' and 'actin filament organization'. Through further integrated analysis of DNA methylation and RNA sequencing, three epigenetically regulated genes were selected: thymus cell antigen 1, theta (Thy1), myosin VI (Myo6), and filamin A-interacting protein 1-like (Filip1l). The methylation level of Thy1 decreased and its mRNA levels increased, whereas that of Myo6 and Filip1l increased and their mRNA levels decreased. The common functions of these three genes may be associated with the neural cytoskeleton and synaptic plasticity. CONCLUSIONS: We suggest that the candidate genes epigenetically play a role in AD-associated neuropathology (i.e., amyloid-beta plaques) and memory deficit by influencing neural structure and synaptic plasticity. Furthermore, counteracting dysregulated epigenetic changes may delay or ameliorate AD onset or symptoms.
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Doença de Alzheimer , Metilação de DNA , Modelos Animais de Doenças , Hipocampo , Camundongos Transgênicos , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Hipocampo/metabolismo , Camundongos , Expressão Gênica , Epigênese Genética , Estudo de Associação Genômica Ampla , Masculino , Humanos , Camundongos Endogâmicos C57BLRESUMO
In patients with high-level radiation exposure, gastrointestinal injury is the main cause of death. Despite the severity of damage to the gastrointestinal tract, no specific therapeutic option is available. Tauroursodeoxycholic acid (TUDCA) is a conjugated form of ursodeoxycholic acid that suppresses endoplasmic reticulum (ER) stress and regulates various cell-signaling pathways. We investigated the effect of TUDCA premedication in alleviating intestinal damage and enhancing the survival of C57BL/6 mice administered a lethal dose (15Gy) of focal abdominal irradiation. TUDCA was administered to mice 1 h before radiation exposure, and reduced apoptosis of the jejunal crypts 12 h after irradiation. At later timepoint (3.5 days), irradiated mice manifested intestinal morphological changes that were detected via histological examination. TUDCA decreased the inflammatory cytokine levels and attenuated the decrease in serum citrulline levels after radiation exposure. Although radiation induced ER stress, TUDCA pretreatment decreased ER stress in the irradiated intestinal cells. The effect of TUDCA indicates the possibility of radiation therapy for cancer in tumor cells. TUDCA did not affect cell proliferation and apoptosis in the intestinal epithelium. TUDCA decreased the invasive ability of the CT26 metastatic colon cancer cell line. Reduced invasion after TUDCA treatment was associated with decreased matrix metalloproteinase (MMP)-7 and MMP-13 expression, which play important roles in invasion and metastasis. This study shows a potential role of TUDCA in protecting against radiation-induced intestinal damage and inhibiting tumor cell migration without any radiation and radiation therapy effect.
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Apoptose , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL , Protetores contra Radiação , Ácido Tauroquenodesoxicólico , Animais , Ácido Tauroquenodesoxicólico/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Protetores contra Radiação/farmacologia , Camundongos , Masculino , Intestinos/efeitos da radiação , Intestinos/efeitos dos fármacos , Intestinos/patologia , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiaçãoRESUMO
Although there are several types of radiation exposure, it is debated whether lowdoserate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiationsensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiationinduced transcriptional alterations. Reverse transcriptionquantitative (RTq) PCR was used to examine time and dosedependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RTqPCR detection and results showed that only Na+/K+ transporting subunit α4, glucose6phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiationsusceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this.
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Glucose-6-Fosfatase , Doenças Inflamatórias Intestinais , Mucina-6 , Animais , Masculino , Camundongos , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Glucose-6-Fosfatase/metabolismo , Glucose-6-Fosfatase/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/patologia , Intestinos/efeitos da radiação , Intestinos/patologia , Jejuno/efeitos da radiação , Jejuno/metabolismo , Jejuno/patologia , Camundongos Endogâmicos BALB C , Mucina-6/metabolismo , Mucina-6/genéticaRESUMO
Radiation therapy targeting the central nervous system is widely utilized for the management of various brain tumors, significantly prolonging patient survival. Presently, investigations are assessing both clinical and preclinical applications of low-dose radiation (LDR) for the treatment of neuropathological conditions beyond tumor therapy. Special focus is given to refractory neurodegenerative diseases linked to neuroinflammation, such as Alzheimer's and Parkinson's diseases, where LDR has shown promising results. This comprehensive review examines the existing experimental data regarding the utilization of LDR in neurological disorders. It covers potential advantages in reducing neurodegenerative alterations and inflammation, as well as possible adverse effects, including neurological impairments. The review underscores the importance of the exposure protocol and the age at which LDR is administered in the context of the nervous system's pathological and physiological states, as these elements are crucial in determining LDR's therapeutic and toxic outcomes. The article concludes with a discussion on the future directions and challenges in optimizing LDR use, aiming to reduce toxicity while effectively managing neurological disorders.
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Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/radioterapia , Animais , Dosagem Radioterapêutica , Doenças Neurodegenerativas/radioterapia , Doenças Neurodegenerativas/terapia , Radioterapia/métodos , Radioterapia/efeitos adversos , Relação Dose-Resposta à RadiaçãoRESUMO
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.
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Biologia Computacional , Vasos Coronários , Relação Dose-Resposta à Radiação , Células Endoteliais , Transcriptoma , Humanos , Vasos Coronários/efeitos da radiação , Vasos Coronários/citologia , Células Endoteliais/efeitos da radiação , Células Endoteliais/metabolismo , Transcriptoma/efeitos da radiação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos da radiação , Doses de Radiação , Transdução de Sinais/efeitos da radiaçãoRESUMO
BACKGROUND: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines. METHODS: We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs. RESULTS: Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs. CONCLUSIONS: Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.
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Doenças Cardiovasculares , Metilação de DNA , Humanos , Epigenoma , Células Endoteliais , Doenças Cardiovasculares/genética , Biomarcadores , Radiação Ionizante , Proteínas de Membrana/genética , Receptores de Progesterona/genéticaRESUMO
PURPOSE: Due to the expanding repertoire of treatment devices that use radiation, the possibility of exposure to both low-dose and high-dose radiation continues to increase. Skin is the outermost part of the body and thus directly exposed to radiation-induced damage. In particular, the skin of diabetes patients is fragile and easily damaged by external stimuli, such as radiation. However, damage and cellular responses induced by ionizing irradiation in diabetic skin have not been explored in detail. In this study, we investigated the effects of several irradiation dose on normal keratinocytes and those from type II diabetes patients, with particular focus on DNA damage. MATERIALS AND METHODS: Cellular responses to low-dose radiation (0.1 Gy) and high-dose radiation (0.5 and 2 Gy) were evaluated. Cell cycle analysis was conducted via flow cytometry and cell viability analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Proteins related to the DNA damage response (DDR) and repair signaling pathways and apoptosis were detected via immunoblot analysis. Apoptosis and cell differentiation were additionally examined in 3D skin organoids using immunohistochemistry. RESULTS: Compared to respective control groups, no significant changes were observed in cell cycle, DDR and repair mechanisms, cell survival, and differentiation in response to 0.1 Gy irradiation in both normal and diabetes type II keratinocytes. On the other hand, the cell cycle showed an increase in the G2/M phase in both cell types following exposure to 2 Gy irradiation. At radiation doses 2 Gy, activation of the DDR and repair signaling pathways, apoptosis, and cell differentiation were increased and viability was decreased in both cell types. Notably, these differences were more pronounced in normal than diabetes type II keratinocytes. CONCLUSIONS: Normal keratinocytes respond more strongly to radiation-induced damage and recovery than diabetes type II keratinocytes.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/radioterapia , Queratinócitos/efeitos da radiação , Radiação Ionizante , Doses de Radiação , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Apoptose/efeitos da radiação , Relação Dose-Resposta à RadiaçãoRESUMO
High-dose radiation (HDR) is widely used for cancer treatment, but the effectiveness of low-dose radiation (LDR) in the treatment of various diseases is controversial. Therefore, to safely utilize LDR for therapeutic purposes, further research on its numerous biological effects of LDR is required. Interest in the increased use of medical imaging devices or the effects of surrounding living environmental radiation on the human body, particularly on fibrosis, is rapidly increasing. Therefore, this study aimed to verify the relationship between LDR and pulmonary fibrosis by evaluating the changes in fibroblasts after LDR treatment and their associated signaling mechanisms. LDR increased the expression of fibrosis markers COL1A1 and α-SMA, cell proliferation, and migration by activating YAP1 and Twist in fibroblasts. Meanwhile, miRNA was employed as a tool to inhibit LDR-induced fibrosis and it was found that miR-765 simultaneously targeted COL1A1, α-SMA, and YAP1. At the cellular level, miR-765 reduced the proliferation and migration of fibroblasts by suppressing the expression of LDR-induced fibrosis factors COL1A1, α-SMA, and YAP1. The efficacy of miR-765 in vivo was confirmed using bleomycin (BLM)-induced fibrotic mouse model. The characteristics of pulmonary fibrosis were reduced after injection of miR-765-overexpressing cells into BLM-induced fibrotic mice. In addition, the suppression of miR-765 expression in the plasma of patients with pulmonary fibrosis confirmed the negative relationship between pulmonary fibrosis and miR-765 expression. Therefore, this study demonstrates that miR-765 is a potential novel diagnostic biomarker and major target for the development of therapeutic agents to inhibit pulmonary fibrosis.
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Low-dose radiation is generally considered less harmful than high-dose radiation. However, its impact on ovaries remains debated. Since previous reports predominantly employed low-dose radiation delivered at a high dose rate on the ovary, the effect of low-dose radiation at a low dose rate on the ovary remains unknown. We investigated the effect of low-dose ionizing radiation delivered at a low dose rate on murine ovaries. Three- and ten-week-old mice were exposed to 0.1 and 0.5 Gy of radiation at a rate of 6 mGy/h and monitored after 3 and 30 days. While neither body weight nor ovarian area showed significant changes, ovarian cells were damaged, showing apoptosis and a decrease in cell proliferation after exposure to 0.1 and 0.5 Gy radiation. Follicle numbers decreased over time in both age groups proportionally to the radiation dose. Younger mice were more susceptible to radiation damage, as evidenced by decreased follicles in 3-week-old mice after 30 days of 0.1 Gy exposure, while 10-week-old mice showed reduced follicles only following 0.5 Gy exposure. Primordial or primary follicles were the most vulnerable to radiation. These findings suggest that even low-dose radiation, delivered at a low dose rate, can adversely affect ovarian function, particularly in the early follicles of younger mice.
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Folículo Ovariano , Ovário , Feminino , Camundongos , AnimaisRESUMO
We have previously found that long-term effects of exposure to radiofrequency electromagnetic fields in 5×FAD mice with severe late-stage Alzheimer's disease reduced both amyloid-ß deposition and glial activation, including microglia. To examine whether this therapeutic effect is due to the regulation of activated microglia, we analyzed microglial gene expression profiles and the existence of microglia in the brain in this study. 5×FAD mice at the age of 1.5 months were assigned to sham- and radiofrequency electromagnetic fields-exposed groups and then animals were exposed to 1950 MHz radiofrequency electromagnetic fields at a specific absorption rate of 5 W/kg for 2 hours/day and 5 days/week for 6 months. We conducted behavioral tests including the object recognition and Y-maze tests and molecular and histopathological analysis of amyloid precursor protein/amyloid-beta metabolism in brain tissue. We confirmed that radiofrequency electromagnetic field exposure for 6 months ameliorated cognitive impairment and amyloid-ß deposition. The expression levels of Iba1 (pan-microglial marker) and colony-stimulating factor 1 receptor (CSF1R; regulates microglial proliferation) in the hippocampus in 5×FAD mice treated with radiofrequency electromagnetic fields were significantly reduced compared with those of the sham-exposed group. Subsequently, we analyzed the expression levels of genes related to microgliosis and microglial function in the radiofrequency electromagnetic fields-exposed group compared to those of a CSF1R inhibitor (PLX3397)-treated group. Both radiofrequency electromagnetic fields and PLX3397 suppressed the levels of genes related to microgliosis (Csf1r, CD68, and Ccl6) and pro-inflammatory cytokine interleukin-1ß. Notably, the expression levels of genes related to microglial function, including Trem2, Fcgr1a, Ctss, and Spi1, were decreased after long-term radiofrequency electromagnetic field exposure, which was also observed in response to microglial suppression by PLX3397. These results showed that radiofrequency electromagnetic fields ameliorated amyloid-ß pathology and cognitive impairment by suppressing amyloid-ß deposition-induced microgliosis and their key regulator, CSF1R.
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PURPOSE: Although the adverse health risks associated with low-dose radiation (LDR) are highly debated, relevant data on neuronal function following chronic LDR exposure are still lacking. MATERIALS AND METHODS: To confirm the effect of chronic LDR on the progression of Alzheimer's disease (AD), we investigated changes in behavior and neuroinflammation after radiation exposure in wild-type (WT) and 5xFAD (TG) mice, an animal model of AD. WT and TG mice, classified by genotyping, were exposed to low-dose-rate radiation for 112 days, with cumulative doses of 0, 0.1, and 0.3 Gy, then evaluated using the open-field and Y-maze behavioral function tests. Changes in the levels of APP processing- and neuroinflammation-related genes were also investigated. RESULTS: No apparent change was evident in either non-spatial memory function or locomotor activity, as examined by the Y-maze and open field tests, respectively. Although chronic LDR did not affect the levels of APP processing, gliosis (Iba1 and GFAP), or inflammatory cytokines (IL-1ß, IL-6, and TNF-α), the levels of IFN-γ were significantly downregulated in TG mice following LDR exposure. In an additional analysis, we examined the genes related to IFN signaling and found that the levels of interferon induced transmembrane protein 3 (IFITM3) were decreased significantly in TG mice following LDR with 0.1 or 0.3 Gy. CONCLUSIONS: Therefore, this study revealed the possibility that LDR could affect the progression of AD, which may be associated with decreased IFN-related signaling, especially IFITM3. Our findings suggest that further studies are required regarding the potential role of LDR in the progression of AD.
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Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Modelos Animais de Doenças , Imunidade Inata , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doenças Neuroinflamatórias , Radiação IonizanteRESUMO
Inflammatory bowel diseases could be diagnosed in major measure by diagnostic imaging; however, radiation exposure in the intestine may also contribute to the progression of these pathologies. To better understand the impact of radiation in the presence of bowel disease, we administered dextran sodium sulfate (DSS) to C57BL/6 mice to induce colitis and exposed to radiation at abdominal area. We observed that abdominal irradiation (13 Gy) aggravates the DSS-induced decrease in survival rate (0%), body weight (74.54 ± 3.59%) and colon length (4.98 ± 0.14 cm). Additionally, abdominal irradiation markedly increased in colonic inflammation levels (3.16 ± 0.16) compared with that of DSS-induced sham mice. Furthermore, abdominal irradiation also increased the mRNA expression levels of inflammatory genes, such as cyclooxygenase-2 (13.10 folds), interleukin-6 (48.83 folds) and tumor necrosis factor-alpha (42.97 folds). We conclude that abdominal irradiation aggravates the detrimental effects of DSS-induced colitis in mice, which might be a useful guideline for inflammatory bowel disease patients.
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Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Interleucina-6/efeitos adversos , Interleucina-6/genética , Interleucina-6/metabolismo , Sulfato de Dextrana/efeitos adversosRESUMO
PURPOSE: Many novel devices such as induction cookers or wireless power transfer produce electromagnetic fields (EMFs) in the intermediate frequency (IF) range (300 Hz to 10 MHz) and it is very meaningful for summarizing the bioeffects of IF-EMF research, particularly animal studies. This review takes into account experimental studies that used murine models to study the health effects of exposure to IF-EMF. The analyses included here use data available in the literature published from January 1988 to August 2021 including the animal studies about general adverse effects, tumorigenic effects, and effects on developmental stages. The studies that linked IF-EMF exposure during pregnancy or neonatal stage to behavioral and cognition changes were included. Additionally, this review also covers the effects of IF-EMF on gene expression patterns in the brain, behavior patterns associated with learning and memory, and immune function. CONCLUSIONS: Although most studies have suggested that IF-EMF is harmless, some adverse effects have been reported after exposure at developmental stages and prolonged exposure. Compared to extremely low frequency (ELF) or radiofrequency (RF) EMF bands, studies on health effects with more diverse perspectives of IF-EMF have not been conducted. Therefore, performing more research should be necessary using the latest biomedical tools. From this point of view, a comprehensive review of IF-EMF studies, particularly animal studies, will provide a valuable basis for further risk analysis in humans.
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Encéfalo , Campos Eletromagnéticos , Humanos , Camundongos , Animais , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , AprendizagemRESUMO
Radiofrequency radiation (RFR) can generate heat in living organisms. In this study, we monitored the body temperature of healthy animals during RFR exposure in real time using an implantable iButton data logger. A reverberation chamber system for small animals was used for this radiofrequency (RF) exposure in vivo study. Healthy male Sprague-Dawley rats were divided into two groups: with versus without iButton implantation (n = 20 per group). Each group was further divided into a sham-exposed and RF-exposed group (n = 10 per subgroup). Rats were exposed to a 1,760-MHz long-term evolution (LTE) signal in the reverberation chamber system at a whole-body average specific absorption rate of 0 W/kg (sham-exposed) or 4 W/kg (RF-exposed) for 6 h. The body temperature of iButton-implanted rats was recorded using an intraperitoneally implanted iButton every minute over 6 h of RF exposure, whereas that of non-implanted rats was measured directly using a rectal thermometer immediately before and after the 6-h RF exposure period. The temperature values measured by the two types of thermometers were significantly positively correlated (r = 0.63, P < 0.01, linear regression), and changes in body temperatures recorded in iButton-implanted and non-implanted rats measured using two thermometers after 6 h of RF exposure were maintained within <1°C (P = 0.87, general linear model, followed by univariate model). Similar results were obtained for rectal thermometer measurements (P = 0.12, paired t-test). These results suggest that RF exposure at a whole-body average specific absorption rate of 4 W/kg does not induce significant changes in body temperature in healthy rats over a 6-h RF exposure period.
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Temperatura Corporal , Ondas de Rádio , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Temperatura Alta , Modelos LinearesRESUMO
The larvae of Protaetia brevitarsis seulensis have been used as a food ingredient and are known for their nutritional value and anti-inflammatory properties. However, whether P. brevitarsis seulensis larvae demonstrate protective effects against radiation-induced testicular injury has not been investigated. In this study, the protective effects of an aqueous extract of P. brevitarsis seulensis larvae (PBE) against radiation-induced testicular injury were tested. Male C57BL/6 mice were administered PBE (5 or 10 mg/kg) orally for 14 days before exposure to focal pelvic irradiation. Histopathological examinations were conducted at 8 h and 30 d after radiation exposure. PBE pretreatment reduced the radiation-induced apoptosis of germ cells at 8 h after irradiation and significantly increased testis and epididymis weights relative to those of the irradiated control mice at 30 days. PBE protected against histopathological damage and decreased the radiation-induced effects on the epithelium height and seminiferous tubule diameter. Furthermore, the extract ameliorated the radiation-induced morphological abnormalities of sperm cells and improved their motility. It also prevented a decrease in the epididymal sperm count caused by irradiation. Moreover, the extract alleviated the generation of reactive oxygen species, and its antioxidative activity increased in a dose-dependent manner. Among the six major compounds isolated from PBE, benzoic acid and uridine showed the highest antioxidant activities. These results suggest that PBE protects against radiation-induced testicular injury via its antioxidative properties. Thus, it has potential clinical applicability as a neoadjuvant therapy for the prevention of testicular damage caused by cancer radiotherapy.
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The physiological or dietary advantages of germinated grains have been the subject of numerous discussions over the past decade. Around 23 million tons of oats are consumed globally, making up a sizeable portion of the global grain market. Oat seedlings contain more protein, beta-glucan, free amino acids, and phenolic compounds than seeds. The progressive neurodegenerative disorder of Alzheimer's is accompanied by worsening memory and cognitive function. A key indicator of this disorder is the unusual buildup of amyloid-beta protein (or Aß) in human brains. In this context, oat seedling extract (OSE) has been identified as a new therapeutic candidate for AD, due to its antioxidant activity and AD-specific mechanism of action. This study directly investigated how OSE affected AD and its impacts by examining the cognitive function and exploring the inflammatory response mechanism. The dried oat seedlings were grounded finely with a grinder, inserted with 50% fermented ethanol 10 times (w/v), and extracted by stirring for 10 h at 45 °C. After filtering the extract by 0.22 um filter, some of it was used for UHPLC analysis. The results indicated that the treatment with OSE protects against Aß25-35-induced cytotoxicity in BV2 cells. Tg-5Xfad AD mice had strong deposition of Aß throughout their brains, while WT mice did not exhibit any such deposition within their brains. A drastic reduction was observed in terms of numbers, as well as the size, of Aß plaques within Tg-5Xfad AD mice exposed to OSE. This study indicated OSE's neuroprotective impacts against neurodegeneration, synaptic dysfunction, and neuroinflammation induced by amyloid-beta. Our results suggest that OSE acts as a neuroprotective agent to combat AD-specific apoptotic cell death, neuroinflammation, amyloid-beta accumulation, as well as synaptic dysfunction in AD mice's brains. Furthermore, the study indicated that OSE treatment affects JNK/ERK/p38 MAPK signaling, with considerable inhibition in p-JNK, p-p38, and p-ERK levels seen in the brain of OSE-treated Tg-5Xfad AD mice.
Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , beta-Glucanas , Doença de Alzheimer/metabolismo , Aminoácidos/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Avena , Modelos Animais de Doenças , Etanol , Humanos , Camundongos , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Plântula/metabolismo , beta-Glucanas/uso terapêutico , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.
RESUMO
We investigated the effects of low dose rate radiation (LDR) on M1 and M2 macrophages in an ovalbumin-induced mouse model of allergic airway inflammation and asthma. After exposure to LDR (1 Gy, 1.818 mGy/h) for 24 days, mice were euthanized and the changes in the number of M1 and M2 macrophages in the bronchoalveolar lavage fluid and lung, and M2-associated cytokine levels, were assessed. LDR treatment not only restored the M2-rich microenvironment but also ameliorated asthma-related progression in a macrophage-dependent manner. In an ovalbumin-induced mouse model, LDR treatment significantly inhibited M2, but not M1, macrophage infiltration. M2-specific changes in macrophage polarization during chronic lung disease reversed the positive effects of LDR. Moreover, the levels of cytokines, including chemokine (C-C motif) ligand (CCL) 24, CCL17, transforming growth factor beta 1, and matrix metalloproteinase-9, decreased in ovalbumin-sensitized/challenged mice upon exposure to LDR. Collectively, our results indicate that LDR exposure suppressed asthmatic progression, including mucin accumulation, inflammation, and Type 2 T helper (Th2) cytokine (interleukin (IL)-4 and IL-13) production. In conclusion, LDR exposure decreased Th2 cytokine secretion in M2 macrophages, resulting in a reduction in eosinophilic inflammation in ovalbumin-sensitized/challenged mice.