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1.
J Drugs Dermatol ; 23(7): 515-518, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954626

RESUMO

BACKGROUND: Visual casts and discoloration are common barriers to sunscreen use in melanin-rich populations. However, photoprotective measures are essential for individuals with all skin types, including darker skin. METHODS: Single-center, 7-day, open-label study of healthy adult females with Fitzpatrick Skin Types (FST) IV to VI and sensitive skin treated with once-daily daily facial moisturizer sun protection factor 35 (DFM SPF35). Subjects completed a cosmetic acceptability questionnaire at days 1 and 7. Photography using VISIA CR was performed at day 7. Adverse events were monitored throughout the study. RESULTS: Thirty-two (32) subjects participated; 31.3% had FST IV, 53.1% V, and 15.6% VI skin. DFM SPF35 was viewed as cosmetically elegant. At day 1, 96.7% of subjects agreed product was easy to apply; 90.0% reported soft skin after product use; 86.7% said it had a lightweight, non-greasy feel and hydrated the skin. At day 7, 93.7% reported no visible white residue on their skin and said the product applied easily/absorbed well. The majority (90.6%) would continue using and would recommend the product; and 87.5% reported the product blended seamlessly into their skin, which agreed with clinical photography. Responses were consistent among subjects with normal, oily, or combination skin. No adverse events were reported. CONCLUSIONS: DFM SPF35 blended well into the skin and was perceived favorably among subjects with SOC after 1 and 7 days of use. Subjects felt it had good cosmetic acceptability without unacceptable white residues or a greasy feeling. Dermatologists need to be versed in products that can be used on a variety of skin types.J Drugs Dermatol. 2024;23(7):515-518.  doi:10.36849/JDD.8223.


Assuntos
Fotografação , Pigmentação da Pele , Fator de Proteção Solar , Protetores Solares , Humanos , Feminino , Protetores Solares/administração & dosagem , Protetores Solares/química , Protetores Solares/efeitos adversos , Adulto , Pessoa de Meia-Idade , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Adulto Jovem , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Pele/diagnóstico por imagem , Administração Cutânea , Inquéritos e Questionários , Creme para a Pele/administração & dosagem , Creme para a Pele/efeitos adversos , Creme para a Pele/química
2.
J Drugs Dermatol ; 23(7): 504-509, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954621

RESUMO

Photoaging is a complex, ongoing process that clinically manifests as cutaneous rhytides, atrophy, laxity, dyspigmentation, telangiectasias, roughness, and mottled appearance of the skin. There is an abundance of research establishing the mechanism of ultraviolet (UV) - induced photodamage as it is a significant source of photoaging and skin cancers. While UV damage is known to induce photoaging, it is important to understand how other forms of light radiation also contribute to this process. UV only constitutes 5 to 10% of solar radiation that reaches the earth's surface. The remaining nearly 90% is evenly split between infrared and visible light radiation. Early research shows that varied skin types may elicit different photobiologic responses to light. This article presents the mechanisms and biomarkers of photodamage induced by light from across the spectrum, including UV, visible light, and infrared to better prevent and reverse the damage of photoaging in all skin types.J Drugs Dermatol. 2024;23(7):504-509.  doi:10.36849/JDD.7438.


Assuntos
Envelhecimento da Pele , Pele , Raios Ultravioleta , Envelhecimento da Pele/efeitos da radiação , Humanos , Raios Ultravioleta/efeitos adversos , Pele/efeitos da radiação , Pele/patologia , Raios Infravermelhos/efeitos adversos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/etiologia
3.
J Drugs Dermatol ; 23(7): 538-544, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954629

RESUMO

BACKGROUND: All skin tones need to be protected from the damaging effects of solar radiation. Although mineral sunscreens offer protection, they can have a thick, greasy feel and leave a white cast, particularly on darker skin tones. Tints offset white cast and provide visible light protection; however, patients may prefer a sheer option. Therefore, a multifunctional, sheer, 100% mineral sunscreen moisturizer (MSM) with broad-spectrum SPF 50 was developed to have positive aesthetics and deliver anti-aging and skin health benefits to all skin tones.  Methods: An IRB-approved, 12-week, open-label clinical study was conducted to investigate the efficacy and tolerability of the MSM. Thirty-nine (39) females aged 35 to 60 years with moderate-severe overall facial photodamage and representing all Fitzpatrick skin types (FST) were recruited. Participants applied the MSM to the face and neck in the morning and reapplied per US Food and Drug Administration requirements. Efficacy and tolerability grading, photography, ultrasound imaging, corneometer measurements, and questionnaires were completed at baseline and weeks 4, 8, and 12.  Results: Statistically significant progressive improvements were demonstrated from baseline to week 12. At week 12, 23.4% and 26.5% mean improvements in overall photodamage were seen for FST I-III and FST IV-VI, respectively. Favorable tolerability was shown for both the face and neck. Photography corroborated clinical grading, and ultrasound imaging indicated a trend in skin density improvement. The MSM was well-perceived.  Conclusion: The MSM is an efficacious and well-tolerated product for patients of all skin tones who desire a sheer, 100% mineral sunscreen moisturizer with anti-aging and skin health benefits. J Drugs Dermatol. 2024;23(7):538-544.  doi:10.36849/JDD.8082.


Assuntos
Envelhecimento da Pele , Pigmentação da Pele , Protetores Solares , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Protetores Solares/administração & dosagem , Protetores Solares/efeitos adversos , Envelhecimento da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Creme para a Pele/administração & dosagem , Creme para a Pele/efeitos adversos , Face , Resultado do Tratamento , Administração Cutânea , Fator de Proteção Solar
4.
Lasers Med Sci ; 39(1): 169, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958682

RESUMO

The quality of life (QoL) and sleep quality are closely linked to the physical and psychological health of end-stage renal disease (ESRD) patients, especially those underwent hemodialysis (HD) therapy. This study aims to investigate the impact of 830 nm laser treatment on improving QoL and sleep quality in HD patients. Forty ESRD patients participated in this study. 830 nm laser was used to radiate on the palm (at dose of 256.10 J/cm2), ST 36 and KI 1 acupoints (at dose of 109.76 J/cm2) of HD patients, and QoL and sleep quality questionnaires were utilized to assess changes following the treatment. After 830 nm laser radiation, lower global Pittsburgh Sleep Quality Index and Athens Insomnia Scale scores were observed, accompanied by higher physical and mental component summary scores in MOS 36-item short-form health survey version 2 and a global World Health Organization Quality of Life Brief Version score. The laser group also showed significant improvements in QoL and sleep quality indicators. Additionally, pain levels decreased on the third day and after one month according to visual analogue scale. This study revealed the positive effects of 830 nm laser on palm, KI 1 and ST 36 acupoints for improving the QoL and sleep quality in ESRD patients underwent HD treatment. The results suggest that 830 nm laser applied to specific targets could be used as a complementary and alternative approach to increase the QoL and sleep quality in ESRD patients.


Assuntos
Falência Renal Crônica , Terapia com Luz de Baixa Intensidade , Qualidade de Vida , Diálise Renal , Qualidade do Sono , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Falência Renal Crônica/terapia , Falência Renal Crônica/psicologia , Falência Renal Crônica/complicações , Terapia com Luz de Baixa Intensidade/métodos , Adulto , Idoso , Sono/efeitos da radiação , Inquéritos e Questionários , Pontos de Acupuntura
5.
Int J Nanomedicine ; 19: 6463-6483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946882

RESUMO

Purpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection. Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF). Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway. Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.


Assuntos
Apoptose , Cério , Hematopoese , Mitocôndrias , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Animais , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Hematopoese/efeitos dos fármacos , Hematopoese/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Humanos , Proteção Radiológica/métodos , Linhagem Celular
6.
Int J Nanomedicine ; 19: 6499-6513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946887

RESUMO

Purpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.


Assuntos
Nanopartículas , Terapia Fototérmica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espécies Reativas de Oxigênio , Animais , Terapia Fototérmica/métodos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Linhagem Celular Tumoral , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Camundongos , Indóis/farmacologia , Indóis/química , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/radioterapia , Neoplasias/terapia , Neoplasias/metabolismo , Nanomedicina
7.
Nat Commun ; 15(1): 5501, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951486

RESUMO

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions' contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.


Assuntos
Luz , Camundongos Endogâmicos C57BL , Neurônios , Córtex Pré-Frontal , Células Ganglionares da Retina , Animais , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos da radiação , Córtex Pré-Frontal/citologia , Camundongos , Células Ganglionares da Retina/fisiologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/efeitos da radiação , Masculino , Neurônios/fisiologia , Neurônios/metabolismo , Neurônios/efeitos da radiação , Estimulação Luminosa , Potenciais de Ação/fisiologia
8.
Nat Commun ; 15(1): 5578, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956103

RESUMO

Diatoms often outnumber other eukaryotic algae in the oceans, especially in coastal environments characterized by frequent fluctuations in light intensity. The identities and operational mechanisms of regulatory factors governing diatom acclimation to high light stress remain largely elusive. Here, we identified the AUREO1c protein from the coastal diatom Phaeodactylum tricornutum as a crucial regulator of non-photochemical quenching (NPQ), a photoprotective mechanism that dissipates excess energy as heat. AUREO1c detects light stress using a light-oxygen-voltage (LOV) domain and directly activates the expression of target genes, including LI818 genes that encode NPQ effector proteins, via its bZIP DNA-binding domain. In comparison to a kinase-mediated pathway reported in the freshwater green alga Chlamydomonas reinhardtii, the AUREO1c pathway exhibits a faster response and enables accumulation of LI818 transcript and protein levels to comparable degrees between continuous high-light and fluctuating-light treatments. We propose that the AUREO1c-LI818 pathway contributes to the resilience of diatoms under dynamic light conditions.


Assuntos
Aclimatação , Diatomáceas , Luz , Diatomáceas/metabolismo , Diatomáceas/genética , Diatomáceas/efeitos da radiação , Chlamydomonas reinhardtii/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/efeitos da radiação , Proteínas de Algas/metabolismo , Proteínas de Algas/genética , Regulação da Expressão Gênica/efeitos da radiação
9.
Radiat Oncol ; 19(1): 85, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956684

RESUMO

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.


Assuntos
Fótons , Neoplasias da Próstata , Receptores Androgênicos , Transdução de Sinais , Transcriptoma , Proteína Supressora de Tumor p53 , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Proteína Supressora de Tumor p53/metabolismo , Transcriptoma/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Dano ao DNA/efeitos da radiação , Radioterapia com Íons Pesados , Reparo do DNA , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Carbono/farmacologia
10.
Radiat Oncol ; 19(1): 86, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956685

RESUMO

PURPOSE: To apply an independent GPU-accelerated Monte Carlo (MC) dose verification for CyberKnife M6 with Iris collimator and evaluate the dose calculation accuracy of RayTracing (TPS-RT) algorithm and Monte Carlo (TPS-MC) algorithm in the Precision treatment planning system (TPS). METHODS: GPU-accelerated MC algorithm (ArcherQA-CK) was integrated into a commercial dose verification system, ArcherQA, to implement the patient-specific quality assurance in the CyberKnife M6 system. 30 clinical cases (10 cases in head, and 10 cases in chest, and 10 cases in abdomen) were collected in this study. For each case, three different dose calculation methods (TPS-MC, TPS-RT and ArcherQA-CK) were implemented based on the same treatment plan and compared with each other. For evaluation, the 3D global gamma analysis and dose parameters of the target volume and organs at risk (OARs) were analyzed comparatively. RESULTS: For gamma pass rates at the criterion of 2%/2 mm, the results were over 98.0% for TPS-MC vs.TPS-RT, TPS-MC vs. ArcherQA-CK and TPS-RT vs. ArcherQA-CK in head cases, 84.9% for TPS-MC vs.TPS-RT, 98.0% for TPS-MC vs. ArcherQA-CK and 83.3% for TPS-RT vs. ArcherQA-CK in chest cases, 98.2% for TPS-MC vs.TPS-RT, 99.4% for TPS-MC vs. ArcherQA-CK and 94.5% for TPS-RT vs. ArcherQA-CK in abdomen cases. For dose parameters of planning target volume (PTV) in chest cases, the deviations of TPS-RT vs. TPS-MC and ArcherQA-CK vs. TPS-MC had significant difference (P < 0.01), and the deviations of TPS-RT vs. TPS-MC and TPS-RT vs. ArcherQA-CK were similar (P > 0.05). ArcherQA-CK had less calculation time compared with TPS-MC (1.66 min vs. 65.11 min). CONCLUSIONS: Our proposed MC dose engine (ArcherQA-CK) has a high degree of consistency with the Precision TPS-MC algorithm, which can quickly identify the calculation errors of TPS-RT algorithm for some chest cases. ArcherQA-CK can provide accurate patient-specific quality assurance in clinical practice.


Assuntos
Algoritmos , Método de Monte Carlo , Órgãos em Risco , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiocirurgia/métodos , Radiocirurgia/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco/efeitos da radiação , Neoplasias/cirurgia , Neoplasias/radioterapia , Radioterapia de Intensidade Modulada/métodos , Gráficos por Computador
11.
Radiat Oncol ; 19(1): 87, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956690

RESUMO

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.


Assuntos
Aprendizado Profundo , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais , Humanos , Neoplasias Retais/radioterapia , Neoplasias Retais/patologia , Órgãos em Risco/efeitos da radiação , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Adulto , Radioterapia de Intensidade Modulada/métodos
12.
Arh Hig Rada Toksikol ; 75(2): 91-101, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963141

RESUMO

Even at low levels, exposure to ionising radiation can lead to eye damage. However, the underlying molecular mechanisms are not yet fully understood. We aimed to address this gap with a comprehensive in silico approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, and Metascape to identify six key regulator genes associated with radiation-induced eye damage (ATM, CRYAB, SIRT1, TGFB1, TREX1, and YAP1), all of which have physical interactions. Some of the identified molecular functions revolve around DNA repair mechanisms, while others are involved in protein binding, enzymatic activities, metabolic processes, and post-translational protein modifications. The biological processes are mostly centred on response to DNA damage, the p53 signalling pathway in particular. We identified a significant role of several miRNAs, such as hsa-miR-183 and hsamiR-589, in the mechanisms behind ionising radiation-induced eye injuries. Our study offers a valuable method for gaining deeper insights into the adverse effects of radiation exposure.


Assuntos
Mineração de Dados , Radiação Ionizante , Humanos , Lesões por Radiação/genética , Lesões por Radiação/etiologia , Traumatismos Oculares/etiologia , Traumatismos Oculares/genética , Genômica , Dano ao DNA/efeitos da radiação
13.
Elife ; 132024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963418

RESUMO

Tiny animals known as tardigrades use a combination of DNA repair machinery and a novel protein to mend their genome after intense ionizing radiation.


Assuntos
Reparo do DNA , Animais , Tardígrados/fisiologia , Tardígrados/efeitos da radiação , Radiação Ionizante , Dano ao DNA/efeitos da radiação
14.
Clin Transl Sci ; 17(7): e13866, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965809

RESUMO

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.


Assuntos
Antineoplásicos Alquilantes , Testículo , Humanos , Masculino , Testículo/efeitos dos fármacos , Criança , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/etiologia , Infertilidade Masculina/diagnóstico , Animais , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Neoplasias/tratamento farmacológico , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Alquilantes/efeitos adversos , Alquilantes/administração & dosagem
15.
Nat Commun ; 15(1): 5500, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951172

RESUMO

Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit. As crucial sites for generating anti-tumor immunity, DLNs are indispensable for the in situ vaccination effect of radiotherapy. Simultaneously, DLN sparing is often not feasible due to metastatic spread. Using murine models of metastatic disease in female mice, here we demonstrate that delayed (adjuvant), but not neoadjuvant, DLN IR overcomes the detrimental effect of concomitant DLN IR on the efficacy of radio-immunotherapy. Moreover, we identify IR-induced disruption of the CCR7-CCL19/CCL21 homing axis as a key mechanism for the detrimental effect of DLN IR. Our study proposes delayed DLN IR as a strategy to maximize the efficacy of radio-immunotherapy across different tumor types and disease stages.


Assuntos
Inibidores de Checkpoint Imunológico , Linfonodos , Animais , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Feminino , Camundongos , Linfonodos/imunologia , Linfonodos/efeitos da radiação , Linfonodos/patologia , Linhagem Celular Tumoral , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Irradiação Linfática , Modelos Animais de Doenças , Terapia Combinada/métodos , Humanos , Receptores CCR7/metabolismo , Metástase Neoplásica
16.
Int J Nanomedicine ; 19: 6677-6692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975322

RESUMO

Background: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration. Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments. Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice. Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.


Assuntos
Doxorrubicina , Imunoterapia , Polietilenoglicóis , Microambiente Tumoral , Animais , Doxorrubicina/farmacologia , Doxorrubicina/análogos & derivados , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Antígeno B7-H1 , Feminino , Humanos , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos BALB C , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Inibidores de Checkpoint Imunológico/farmacologia , Ondas Ultrassônicas , Terapia Combinada
17.
Cell Biochem Funct ; 42(5): e4092, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978266

RESUMO

Throughout radiotherapy, radiation of the hepatic tissue leads to damage of the hepatocytes. We designed the current study to examine how cerium oxide nanoparticles (CONPs) modulate gamma irradiation-induced hepatotoxicity in rats. Animals received CONPs (15 mg/kg body weight [BW], ip) single daily dose for 14 days, and they were exposed on the seventh day to a single dose of gamma radiation (6 Gy). Results showed that irradiation increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. Furthermore, it elevated oxidative stress biomarker; malondialdehyde (MDA) and inhibited the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in hepatic tissues homogenate. Additionally, hepatic apoptotic markers; caspase-3 (Casp-3) and Casp-9 were elevated and the B-cell lymphoma-2 (Bcl-2) gene level was decreased in rats exposed to radiation dose. We observed that CONPs can modulate these changes, where CONPs reduced liver enzyme activities, MDA, and apoptotic markers levels, in addition, it elevated antioxidant enzyme activities and Bcl-2 gene levels, as well as improved histopathological changes in the irradiated animals. So our results concluded that CONPs had the ability to act as radioprotector defense against hepatotoxicity resulted during radiotherapy.


Assuntos
Antioxidantes , Apoptose , Cério , Raios gama , Fígado , Nanopartículas , Cério/farmacologia , Cério/química , Animais , Raios gama/efeitos adversos , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos , Masculino , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Fígado/metabolismo , Fígado/patologia , Nanopartículas/química , Ratos Wistar , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Alanina Transaminase/metabolismo , Alanina Transaminase/sangue , Malondialdeído/metabolismo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/sangue , Superóxido Dismutase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
18.
BMC Cancer ; 24(1): 832, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992600

RESUMO

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.


Assuntos
Neoplasias de Cabeça e Pescoço , Mitocôndrias , Glândulas Salivares , Xerostomia , Xerostomia/etiologia , Xerostomia/prevenção & controle , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Glândulas Salivares/efeitos da radiação , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/patologia , Lesões por Radiação/prevenção & controle , Lesões por Radiação/etiologia , Animais , Radioterapia/efeitos adversos , Radioterapia/métodos , Qualidade de Vida
19.
Lasers Med Sci ; 39(1): 180, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001934

RESUMO

This study investigates the impact of Photobiomodulation (PBM) at different wavelengths on non-superficial cancer cells. Utilizing three laser protocols (650 nm, 810 nm, and 915 nm), the research explores cytotoxic effects, ROS generation, and cell migration. Results reveal varied responses across cell lines, with 810 nm PBM inducing significant ROS levels and inhibiting PAN-1 cell migration. The study suggests potential therapeutic applications for PBM in non-superficial cancers, emphasizing the need for further exploration in clinical settings.


Assuntos
Movimento Celular , Terapia com Luz de Baixa Intensidade , Espécies Reativas de Oxigênio , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Movimento Celular/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Neoplasias/radioterapia
20.
Electromagn Biol Med ; 43(3): 187-203, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38990565

RESUMO

To enhance our understanding of electroporation and optimize the pulses used within the frequency range of 1 kHz to 100 MHz, with the aim of minimizing side effects such as muscle contraction, we introduce a novel electrical model, structured as a 2D representation employing exclusively lumped elements. This model adeptly encapsulates the intricate dynamics of living cells' impedance variation. A distinguishing attribute of the proposed model lies in its capacity to decipher the distribution of transmembrane potential across various orientations within living cells. This aspect bears critical importance, particularly in contexts such as electroporation and cellular stimulation, where precise knowledge of potential gradients is pivotal. Furthermore, the augmentation of the proposed electrical model with the Hodgkin-Huxley (HH) model introduces an additional dimension. This integration augments the model's capabilities, specifically enabling the exploration of muscle cell stimulation and the generation of action potentials. This broader scope enhances the model's utility, facilitating comprehensive investigations into intricate cellular behaviors under the influence of external electric fields.


In our research, we've introduced an enhanced electrical model for living cells. This model simplifies cell behavior using only basic electrical components like resistors and capacitors. It's designed to mimic the real electrical properties of cells, particularly the cell membrane, which can change in response to electricity at different frequencies, ranging from 1 kHz to 100 MHz. This frequency range is essential for studying processes like electroporation, a technique used in various medical applications.Our model is represented in a two-dimensional structure, making it a handy tool for identifying transmembrane potential distributions, a critical factor in electroporation procedures. This means we can better understand how cells react to electrical impulses, which is crucial for improving electroporation techniques.Additionally, we've extended our model to include muscle cells by incorporating the Hodgkin-Huxley model, a well-established model for understanding electrical behavior in muscle cells. This allows us to study how muscles contract when exposed to different electrical pulses, a common side effect of electroporation procedures. By examining various pulse characteristics, we can determine which ones are best for minimizing muscle contractions during electroporation.In summary, our research has led to the development of a versatile electrical model for living cells. It not only helps us understand how cells respond to electricity in the context of electroporation but also provides insights into muscle contractions and how to optimize electrical pulses for medical treatments.


Assuntos
Potenciais de Ação , Modelos Biológicos , Eletroporação , Sobrevivência Celular/efeitos da radiação , Eletricidade , Humanos
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