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1.
Front Immunol ; 15: 1373497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720889

RESUMO

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.


Assuntos
Neoplasias da Mama , Imunomodulação , Cuidados Intraoperatórios , Mastectomia Segmentar , Microambiente Tumoral , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos da radiação , Imunomodulação/efeitos da radiação , Idoso , Adulto , Terapia Combinada
2.
Mol Biol Rep ; 51(1): 633, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724835

RESUMO

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.


Assuntos
Docetaxel , Nanopartículas Metálicas , Neoplasias da Próstata , Radiossensibilizantes , Prata , Humanos , Docetaxel/farmacologia , Masculino , Prata/farmacologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Linhagem Celular Tumoral , Radiossensibilizantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Peróxido de Hidrogênio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Caspase 3/metabolismo , Caspase 3/genética , Antineoplásicos/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caderinas/metabolismo , Caderinas/genética
3.
Mikrochim Acta ; 191(6): 330, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744738

RESUMO

In view of a large number of people infected with Helicobacter pylori (H. pylori) with great harm followed, there is an urgent need to develop a non-invasive, easy-to-operate, and rapid detection method, and to identify effective sterilization strategies. In this study, highly specific nanoprobes with nanozyme activity, Ag@Pt nanoparticles (NPs) with the antibody, were utilized as a novel lateral flow immunoassay (LFIA). The optical label (Ag@Pt NPs) was enhanced by the introduction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) and compared with a gold nanoparticles (Au NPs) optical label. Under the optimal condition, Ag@Pt-LFIA and TMB-enhanced Ag@Pt-LFIA for H. pylori were successfully established, two of which were over twofold and 100-fold more sensitive than conventional visual Au NP-based LFIA, respectively. Furthermore, Ag@Pt NPs with the antibody irradiated with NIR laser (808 nm) at a power intensity of 550 mW/cm2 for 5 min exhibited a remarkable antibacterial effect. The nanoprobes could close to bacteria through effective interactions between antibodies and bacteria, thereby benefiting photothermal sterilization. Overall, Ag@Pt NPs provide promising applications in pathogen detection and therapeutic applications.


Assuntos
Ligas , Helicobacter pylori , Nanopartículas Metálicas , Platina , Prata , Helicobacter pylori/efeitos da radiação , Helicobacter pylori/efeitos dos fármacos , Prata/química , Nanopartículas Metálicas/química , Platina/química , Ligas/química , Antibacterianos/farmacologia , Antibacterianos/química , Imunoensaio/métodos , Benzidinas/química , Ouro/química , Humanos , Esterilização/métodos , Limite de Detecção
4.
Braz Oral Res ; 38: e034, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747821

RESUMO

The aim of this study was to investigate the effect of acid challenge on the activation of matrix metalloproteinases (MMPs) in the Dentinoenamel junction of primary and permanent teeth submitted to radiotherapy. For this purpose, a total of 178 dental fragments obtained from molars were used, and randomly divided into 2 groups (primary and permanent teeth) / 4 experimental subgroups (irradiated and non-irradiated, demineralized and non-demineralized). The fragments were exposed to radiation, with a dose fraction of 2 Gy, for 5 consecutive days, until a total dose of 60 Gy was reached, with a total of 30 cycles, for 6 weeks. To determine the activity of MMPs on the dentinoenamel junction (DEJ), in situ zymography assays on 0.6mm dental fragments were performed. To assess whether MMP activity would be impacted by an acidic environment, the fragments were placed in a demineralizing solution (pH of 4.8). The finding was that irradiation activated MMPs in DEJ and these effects were more evident in permanent when compared with primary teeth. When the effect of an acid challenge on MMPs activity was investigated, demineralization was observed not to increase MMPs activity in non-irradiated teeth, but it did increase MMPs activity in irradiated teeth. In conclusion, an acid challenge was found to exacerbate activation of MMPs in DEJ of permanent teeth submitted to irradiation, but not in primary teeth.


Assuntos
Metaloproteinases da Matriz , Metaloproteinases da Matriz/metabolismo , Metaloproteinases da Matriz/efeitos da radiação , Metaloproteinases da Matriz/análise , Humanos , Fatores de Tempo , Dente Decíduo/efeitos da radiação , Dente Decíduo/efeitos dos fármacos , Dentina/efeitos da radiação , Dentina/efeitos dos fármacos , Dentina/enzimologia , Dentição Permanente , Distribuição Aleatória , Concentração de Íons de Hidrogênio , Desmineralização do Dente , Estatísticas não Paramétricas , Análise de Variância , Valores de Referência , Ativação Enzimática/efeitos da radiação , Ativação Enzimática/efeitos dos fármacos
5.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731413

RESUMO

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1ß, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.


Assuntos
Arbutina , Envelhecimento da Pele , Raios Ultravioleta , Arbutina/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Humanos , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
6.
Sci Rep ; 14(1): 10787, 2024 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734765

RESUMO

Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.


Assuntos
alfa-Globulinas , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Lutécio , Animais , alfa-Globulinas/metabolismo , Camundongos , Masculino , Humanos , Dipeptídeos/farmacologia , Rim/patologia , Rim/efeitos da radiação , Rim/efeitos dos fármacos , Rim/metabolismo , Compostos Radiofarmacêuticos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/patologia , Nitrogênio da Ureia Sanguínea , Antígeno Prostático Específico
7.
Food Res Int ; 186: 114382, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729736

RESUMO

Black carrot anthocyanins have gained increasing attention as natural coloring agent, owing to their higher stability than anthocyanins from berries. The stability has been attributed to their higher degree of acylation. This study investigated the impact of acylation on the stability of individual anthocyanins during storage in light and darkness. We hypothesized that the acylated anthocyanins would be more stable than the non-acylated ones. The major five anthocyanins were fractioned by semi-preparative HPLC and stored at pH 4.5 in light and darkness to investigate how acylation affected the stability. The stability was evaluated by absorption spectroscopy and mass spectrometry (MS). Two of the anthocyanins were non-acylated; 3-xylosyl(glucosyl)galactoside and cyanidin 3-xylosylgalactoside, and three were acylated; cyanidin 3-xylosyl(sinapolyglucosyl)galacto-side, cyanidin 3-xylosyl(feruloylglu-cosyl)galactoside, and cyanidin 3-xylosyl(coumaroyl-glucosyl)galactoside. Both methods (spectroscopy and MS) showed a clear effect of acylation when stored in light, but surprisingly the two non-acylated anthocyanins, showed higher stability than the three acylated ones.


Assuntos
Antocianinas , Daucus carota , Luz , Antocianinas/química , Antocianinas/análise , Acilação , Daucus carota/química , Daucus carota/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Escuridão , Armazenamento de Alimentos/métodos , Espectrometria de Massas , Concentração de Íons de Hidrogênio
8.
Radiat Environ Biophys ; 63(2): 297-306, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722389

RESUMO

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.


Assuntos
Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Feminino , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radiometria , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Metástase Linfática/radioterapia
9.
Eur J Med Res ; 29(1): 282, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735974

RESUMO

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.


Assuntos
Neoplasias da Mama , Aprendizado de Máquina , Humanos , Feminino , Neoplasias da Mama/radioterapia , Pessoa de Meia-Idade , Adulto , Idoso , Pele/efeitos da radiação , Pele/patologia , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Dosagem Radioterapêutica
10.
Int J Mol Med ; 53(6)2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695243

RESUMO

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low­dose radiation­sensitive markers. The HuT 78 and IM­9 cell lines were irradiated in a concentration­dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration­dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub­lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub­lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML­277, pifithrin­α, and nutlin­3a were evaluated for their ability to modulate radiation­induced cell death. The use of BML­277 led to a decrease in radiation­induced p­CHK2 and γH2AX levels and mitigated radiation­induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation­sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Dano ao DNA , Radiação Ionizante , Transdução de Sinais , Dano ao DNA/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Humanos , Animais , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Camundongos , Quinase do Ponto de Checagem 2/metabolismo , Quinase do Ponto de Checagem 2/genética , Histonas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Masculino , Imidazóis/farmacologia , Protetores contra Radiação/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta à Radiação
11.
Mol Carcinog ; 63(6): 1160-1173, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695641

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, with an escalating incidence rate and a notable potential (up to 5%) for metastasis. Ultraviolet radiation (UVA and UVB) exposure is the primary risk factor for cSCC carcinogenesis, with literature suggesting ultraviolet radiation (UVR) promotes vascular endothelial growth factor A (VEGFA) expression. This study aims to investigate UVR-induced upregulation of VEGFA and explore combination therapeutic strategies. The skin squamous cell carcinoma cell line A431 was exposed to specific durations of ultraviolet radiation. The effect of emodin on ATR/SerRS/VEGFA pathway was observed. The cell masses were also transplanted subcutaneously into mice (n = 8). ATR inhibitor combined with emodin was used to observe the growth and angiogenesis of the xenografts. The results showed that UV treatment significantly enhanced the phosphorylation of SerRS and the expression level of VEGFA in A431 cells (p < 0.05). Treatment with emodin significantly inhibited this expression (p < 0.05), and the combination of emodin and ATR inhibitor further enhanced the inhibitory effect (p < 0.05). This phenomenon was further confirmed in the xenograft model, which showed that the combination of ATR inhibitor and emodin significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.05), thus showing an inhibitory effect on cSCC. This study innovatively reveals the molecular mechanism of UV-induced angiogenesis in cSCC and confirms SerRS as a novel target to inhibit cSCC angiogenesis and progression in vitro and in vivo studies.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma de Células Escamosas , Neovascularização Patológica , Neoplasias Cutâneas , Raios Ultravioleta , Fator A de Crescimento do Endotélio Vascular , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Camundongos , Neovascularização Patológica/metabolismo , Linhagem Celular Tumoral , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Emodina/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Angiogênese
12.
ACS Appl Mater Interfaces ; 16(19): 24410-24420, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709954

RESUMO

Sonophotodynamic antimicrobial therapy (SPDAT) is recognized as a highly efficient biomedical treatment option, known for its versatility and remarkable healing outcomes. Nevertheless, there is a scarcity of sonophotosensitizers that demonstrate both low cytotoxicity and exceptional antibacterial effectiveness in clinical applications. In this paper, a novel ZnO nanowires (NWs)@TiO2-xNy core-sheath composite was developed, which integrates the piezoelectric effect and heterojunction to build dual built-in electric fields. Remarkably, it showed superb antibacterial effectiveness (achieving 95% within 60 min against S. aureus and ∼100% within 40 min against E. coli, respectively) when exposed to visible light and ultrasound. Due to the continuous interference caused by light and ultrasound, the material's electrostatic equilibrium gets disrupted. The modification in electrical properties facilitates the composite's ability to attract bacterial cells through electrostatic forces. Moreover, Zn-O-Ti and Zn-N-Ti bonds formed at the interface of ZnO NWs@TiO2-xNy, further enhancing the dual internal electric fields to accelerate the excited carrier separation to generate more reactive oxygen species (ROS), and thereby boosting the antimicrobial performance. In addition, the TiO2 layer limited Zn2+ dissolution into solution, leading to good biocompatibility and low cytotoxicity. Lastly, we suggest a mechanistic model to offer practical direction for the future development of antibacterial agents that are both low in toxicity and high in efficacy. In comparison to the traditional photodynamic therapy systems, ZnO NWs@TiO2-xNy composites exhibit super piezo-photocatalytic antibacterial activity with low toxicity, which shows great potential for clinical application as an antibacterial nanomaterial.


Assuntos
Antibacterianos , Escherichia coli , Nanofios , Staphylococcus aureus , Titânio , Óxido de Zinco , Titânio/química , Titânio/farmacologia , Titânio/efeitos da radiação , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Nanofios/química , Catálise , Espécies Reativas de Oxigênio/metabolismo , Testes de Sensibilidade Microbiana , Humanos , Luz , Camundongos , Animais
13.
J Cell Mol Med ; 28(10): e18378, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760895

RESUMO

The efficacy of radiotherapy, a cornerstone in the treatment of lung adenocarcinoma (LUAD), is profoundly undermined by radiotolerance. This resistance not only poses a significant clinical challenge but also compromises patient survival rates. Therefore, it is important to explore this mechanism for the treatment of LUAD. Multiple public databases were used for single-cell RNA sequencing (scRNA-seq) data. We filtered, normalized and downscaled scRNA-seq data based on the Seurat package to obtain different cell subpopulations. Subsequently, the ssGSEA algorithm was used to assess the enrichment scores of the different cell subpopulations, and thus screen the cell subpopulations that are most relevant to radiotherapy tolerance based on the Pearson method. Finally, pseudotime analysis was performed, and a preliminary exploration of gene mutations in different cell subpopulations was performed. We identified HIST1H1D+ A549 and PIF1+ A549 as the cell subpopulations related to radiotolerance. The expression levels of cell cycle-related genes and pathway enrichment scores of these two cell subpopulations increased gradually with the extension of radiation treatment time. Finally, we found that the proportion of TP53 mutations in patients who had received radiotherapy was significantly higher than that in patients who had not received radiotherapy. We identified two cellular subpopulations associated with radiotherapy tolerance, which may shed light on the molecular mechanisms of radiotherapy tolerance in LUAD and provide new clinical perspectives.


Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Mutação , Tolerância a Radiação , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/radioterapia , Adenocarcinoma de Pulmão/patologia , Tolerância a Radiação/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Análise de Sequência de RNA/métodos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células A549 , Perfilação da Expressão Gênica , Linhagem Celular Tumoral
14.
J Bodyw Mov Ther ; 38: 314-322, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38763575

RESUMO

BACKGROUND: Photobiomodulation (PBM) is indicated to accelerate the recovery of athletes and reduce muscle damage caused by physical exercise. The objective of this study was to establish the best time to apply photobiomodulation to increase the functional performance and ergogenic response of rugby athletes. METHODS: Randomized crossover clinical trial with 18 rugby athletes of both sexes. The interventions were carried out from January to May 2019. The blood levels of creatine kinase (CK) and lactate, and performance in the Modified Star Excursion Balance Test, Single Hop Test, Triple Hop Test, Bangsbo Sprint test (BST), and Yo-Yo intermittent recovery level 1 (YoyoIR1) were evaluated. The athletes underwent two blocks of exercises with the BST and Yoyo-IR1, as well as the random application of four interventions: without application of photobiomodulation (CO), pre-exercise photobiomodulation (PBpre), PBM during the exercise interval (PBint), or post-exercise photobiomodulation (PBpos). The photobiomodulation using light-emitting diodes (850 nm, 8 J/cm2) lasted 10 min and was applied to the quadriceps, hamstrings, and triceps surae muscles. The results were compared between groups and times, and the effect size for the interventions was established. RESULTS: No differences were found between groups in CK, lactate, and performance in the functional tests between groups and times. Only the PBpre presented improved performance in the first Yoyo-1R1 test (p < 0.01), while the PBint improved in the second Yoyo-IR1 test and BST (p < 0.05). CONCLUSION: The PBM did not change muscle damage markers or performance in the functional tests. For an ergogenic response, photobiomodulation applied before exercise improves performance, which can be maintained when PBM is performed in the exercise interval.


Assuntos
Creatina Quinase , Estudos Cross-Over , Ácido Láctico , Terapia com Luz de Baixa Intensidade , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Masculino , Feminino , Adulto Jovem , Creatina Quinase/sangue , Ácido Láctico/sangue , Adulto , Músculo Esquelético/fisiologia , Músculo Esquelético/efeitos da radiação , Desempenho Atlético/fisiologia , Futebol Americano/fisiologia , Atletas , Desempenho Físico Funcional , Teste de Esforço/métodos
15.
Sci Rep ; 14(1): 11468, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769339

RESUMO

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying 224Ra release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. The distribution of the alpha-particle pits detected by a plastic nuclear track detector, CR-39, strongly correlated with γH2AX staining, a marker of DSBs, around the 224Ra source, but the area of G2 arrested cells was more widely spread 24 h from the start of the exposure. Thereafter, close time-lapse observation revealed varying cell cycle kinetics, depending on the distance from the source. A medium containing daughter nuclides prepared from 224Ra sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages.


Assuntos
Partículas alfa , Quebras de DNA de Cadeia Dupla , Humanos , Células HeLa , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Dano ao DNA/efeitos da radiação , Ciclo Celular/efeitos da radiação , Histonas/metabolismo , Técnicas de Cultura de Células/métodos
16.
Sci Rep ; 14(1): 11502, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769353

RESUMO

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0-2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.


Assuntos
Aberrações Cromossômicas , Linfócitos , Radiação Ionizante , Humanos , Linfócitos/efeitos da radiação , Linfócitos/metabolismo , Masculino , Aberrações Cromossômicas/efeitos da radiação , Raios X/efeitos adversos , Dano ao DNA , Voo Espacial , Partículas alfa/efeitos adversos , Transcrição Gênica/efeitos da radiação , Adulto , Regulação da Expressão Gênica/efeitos da radiação , Relação Dose-Resposta à Radiação
17.
Int J Mol Sci ; 25(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732247

RESUMO

To explore the impact of shade treatment on grape berries, 'Marselan' grape berries were bagged under different light transmission rates (100% (CK), 75% (A), 50% (B), 25% (C), 0% (D)). It was observed that this treatment delayed the ripening of the grape berries. The individual weight of the grape berries, as well as the content of fructose, glucose, soluble sugars, and organic acids in the berries, was measured at 90, 100, and 125 days after flowering (DAF90, DAF100, DAF125). The results revealed that shading treatment reduced the sugar content in grape berries; the levels of fructose and glucose were higher in the CK treatment compared to the other treatments, and they increased with the duration of the shading treatment. Conversely, the sucrose content exhibited the opposite trend. Additionally, as the weight of the grape berries increased, the content of soluble solids and soluble sugars in the berries also increased, while the titratable acidity decreased. Furthermore, 16 differentially expressed genes (DEGs) were identified in the photosynthesis-antenna protein pathway from the transcriptome sequencing data. Correlation analysis revealed that the expression levels of genes VIT_08s0007g02190 (Lhcb4) and VIT_15s0024g00040 (Lhca3) were positively correlated with sugar content in the berries at DAF100, but negatively correlated at DAF125. qRT-PCR results confirmed the correlation analysis. This indicates that shading grape clusters inhibits the expression of genes in the photosynthesis-antenna protein pathway in the grape berries, leading to a decrease in sugar content. This finding contributes to a deeper understanding of the impact mechanisms of grape cluster shading on berry quality, providing important scientific grounds for improving grape berry quality.


Assuntos
Frutas , Regulação da Expressão Gênica de Plantas , Fotossíntese , Proteínas de Plantas , Açúcares , Vitis , Vitis/genética , Vitis/metabolismo , Vitis/efeitos da radiação , Frutas/genética , Frutas/metabolismo , Frutas/efeitos da radiação , Fotossíntese/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Açúcares/metabolismo , Luz
18.
Jt Dis Relat Surg ; 35(2): 455-461, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38727129

RESUMO

Case reports of plexopathy after prostate cancer are usually neoplastic. Radiation-induced lumbosacral plexopathy and insufficiency fractures have clinical significance due to the need to differentiate them from tumoral invasions, metastases, and spinal pathologies. Certain nuances, including clinical presentation and screening methods, help distinguish radiation-induced plexopathy from tumoral plexopathy. This case report highlights the coexistence of these two rare clinical conditions. Herein, we present a 78-year-old male with a history of radiotherapy for prostate cancer who developed right foot drop, severe lower back and right groin pain, difficulty in standing up and walking, and tingling in both legs over the past month during remission. The diagnosis of lumbosacral plexopathy and pelvic insufficiency fracture was made based on magnetic resonance imaging, positron emission tomography, and electroneuromyography. The patient received conservative symptomatic treatment and was discharged with the use of a cane for mobility. Radiation-induced lumbosacral plexopathy following prostate cancer should be kept in mind in patients with neurological disorders of the lower limbs. Pelvic insufficiency fracture should also be considered if the pain does not correspond to the clinical findings of plexopathy. These two pathologies, which can be challenging to diagnose, may require surgical or complex management approaches. However, in this patient, conservative therapies led to an improvement in quality of life and a reduction in the burden of illness.


Assuntos
Fraturas de Estresse , Plexo Lombossacral , Neoplasias da Próstata , Lesões por Radiação , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Idoso , Plexo Lombossacral/lesões , Plexo Lombossacral/efeitos da radiação , Plexo Lombossacral/patologia , Fraturas de Estresse/etiologia , Fraturas de Estresse/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico por imagem , Ossos Pélvicos/lesões , Ossos Pélvicos/patologia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/efeitos da radiação , Doenças do Sistema Nervoso Periférico/etiologia , Imageamento por Ressonância Magnética , Radioterapia/efeitos adversos
19.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731841

RESUMO

Plutella xylostella (Linnaeus) mainly damages cruciferous crops and causes huge economic losses. Presently, chemical pesticides dominate its control, but prolonged use has led to the development of high resistance. In contrast, the sterile insect technique provides a preventive and control method to avoid the development of resistance. We discovered two genes related to the reproduction of Plutella xylostella and investigated the efficacy of combining irradiation with RNA interference for pest management. The results demonstrate that after injecting PxAKT and PxCDK5, there was a significant decrease of 28.06% and 25.64% in egg production, and a decrease of 19.09% and 15.35% in the hatching rate compared to the control. The ratio of eupyrene sperm bundles to apyrene sperm bundles also decreased. PxAKT and PxCDK5 were identified as pivotal genes influencing male reproductive processes. We established a dose-response relationship for irradiation (0-200 Gy and 200-400 Gy) and derived the irradiation dose equivalent to RNA interference targeting PxAKT and PxCDK5. Combining RNA interference with low-dose irradiation achieved a sub-sterile effect on Plutella xylostella, surpassing either irradiation or RNA interference alone. This study enhances our understanding of the genes associated with the reproduction of Plutella xylostella and proposes a novel approach for pest management by combining irradiation and RNA interference.


Assuntos
Quinase 5 Dependente de Ciclina , Proteínas Proto-Oncogênicas c-akt , Interferência de RNA , Animais , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Fertilidade/efeitos da radiação , Fertilidade/genética , Mariposas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Feminino , Reprodução/efeitos da radiação , Reprodução/genética
20.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731895

RESUMO

UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Agaricus blazei Murill (ABM) is an edible medicinal and nutritional fungus. One of its constituents, Agaricus blazei Murill polysaccharide (ABP), has been reported to exhibit antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, which suggests potential effects that protect against photodamage. In this study, a UVB-induced photodamage HaCaT model was established to investigate the potential reparative effects of ABP and its two constituents (A1 and A2). Firstly, two purified polysaccharides, A1 and A2, were obtained by DEAE-52 cellulose column chromatography, and their physical properties and chemical structures were studied. A1 and A2 exhibited a network-like microstructure, with molecular weights of 1.5 × 104 Da and 6.5 × 104 Da, respectively. The effects of A1 and A2 on cell proliferation, the mitochondrial membrane potential, and inflammatory factors were also explored. The results show that A1 and A2 significantly promoted cell proliferation, enhanced the mitochondrial membrane potential, suppressed the expression of inflammatory factors interleukin-1ß (IL-1ß), interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and increased the relative content of filaggrin (FLG) and aquaporin-3 (AQP3). The down-regulated JAK-STAT signaling pathway was found to play a role in the response to photodamage. These findings underscore the potential of ABP to ameliorate UVB-induced skin damage.


Assuntos
Agaricus , Proliferação de Células , Proteínas Filagrinas , Células HaCaT , Raios Ultravioleta , Agaricus/química , Humanos , Raios Ultravioleta/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Citocinas/metabolismo
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