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1.
Talanta ; 281: 126909, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39321559

RESUMEN

4-n-butylresorcinol (4nBR) is a frequently utilized as whitening ingredients in skincare cosmetics. Compared with other whitening ingredients, it can effectively inhibit tyrosinase with lower toxicity and superior inhibition efficacy. Under alkaline conditions, an induced oxidative coupling reaction can occur between 4nBR and dopamine (DA) to generate strong fluorescent substance azamonardine with an intense emission band centering at 476 nm when excited at 440 nm. This phenomenon can be used to establish a fluorescence analysis method for 4nBR. The results indicated that the linear range of the method was 1.0-24.0 nmol L-1, and the detection limit was as low as 0.25 nmol L-1. The method showed high sensitivity, good selectivity, mild experimental conditions and low cost. The proposed method was successfully used to detect 4nBR in cosmetics, and the results were consistent with those of HPLC. The spiking recoveries were between 98.2% and 108 %.


Asunto(s)
Dopamina , Resorcinoles , Espectrometría de Fluorescencia , Resorcinoles/química , Resorcinoles/análisis , Dopamina/análisis , Dopamina/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Cosméticos/química , Cosméticos/análisis , Fluorescencia
2.
Int J Ophthalmol ; 17(10): 1887-1897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39430027

RESUMEN

AIM: To describe the distribution of ocular biometrics and to evaluate its associations with refractive error and to assess the contribution from ocular parameters to refractive error among Chinese myopic children. METHODS: This cross-sectional study evaluated subjects aged 8-12y. Keratometry, ocular biometry, and cycloplegic autorefraction were performed on each subject. Spherical equivalent refraction (SER) and ocular biometrics were assessed as a function of age and gender. The Pearson correlation analysis between SER and ocular biometrics was carried out. Multiple linear regression was performed to analyze the association between SER and ocular parameters. RESULTS: A total of 689 out of 735 participants (321 boys, 48.1%) were analyzed, with a mean SER of -2.98±1.47 diopter (D). Axial length (AL), anterior chamber depth (ACD), corneal radius of curvature (CR), horizontal visible iris diameter (HVID), central corneal thickness (CCT) and lens power (LP) showed normal distribution. The AL, AL/CR ratio, ACD and CR increased from 8 to 12y of age, while SER and LP decreased, HVID and CCT remained stable. There was no difference in gender. SER decreased by 0.929 D for every 1 mm increase in AL and decreased by 1.144 D for every 0.1 increase in AL/CR ratio. The Pearson correlation coefficient between SER and AL was -0.538 (P<0.01) and -0.747 (P<0.01) between SER and AL/CR ratio. For the SER variance, AL explained 29.0%, AL/CR ratio explained 55.7%, while AL, CR, ACD and LP explained 99.3% after adjusting for age and gender. CONCLUSION: The AL, CR, ACD and LP are the most important determinants of myopic refractive error during myopia progression.

3.
Front Microbiol ; 15: 1469953, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39360313

RESUMEN

Growth factor receptor bound protein 7 (GRB7) is reportedly upregulated in human gastric cancer (GC), which is closely associated with tumor progression and prognosis. However, the mechanism underlying its dysregulation in GC remains poorly understood. In this study, we found that GRB7 overexpression was associated with Helicobacter pylori (H. pylori) infection. GC cells (AGS and MGC-803) infection assays revealed that this upregulation was mediated by the transcription factor STAT3, and activation of STAT3 by H. pylori promoted GRB7 expression in infected GC cells. Moreover, CagA, the key virulence factor of H. pylori, was found involved in STAT3-mediated GRB7 overexpression. The overexpressed GRB7 further promoted GC cell proliferation, migration, and invasion by activating ERK signaling. Mice infection was further used to investigate the action of GRB7. In H. pylori infection, GRB7 expression in mice gastric mucosa was elevated, and higher STAT3 and ERK activation were also detected. These results revealed GRB7-mediated pathogenesis in H. pylori infection, in which H. pylori activates STAT3, leading to increased GRB7 expression, then promotes activation of the ERK signal, and finally enhances malignant properties of infected cells. Our findings elucidate the role of GRB7 in H. pylori-induced gastric disorders, offering new prospects for the treatment and prevention of H. pylori-associated gastric carcinogenesis by targeting GRB7.

4.
Small ; : e2407365, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39363827

RESUMEN

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

5.
J Mater Chem B ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39380332

RESUMEN

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer.

6.
J Med Chem ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388678

RESUMEN

Keap1 plays a crucial role in regulating the Nrf2-mediated cytoprotective response and is increasingly targeted for oxidative stress-related diseases. Using small molecules to disrupt the Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a new strategy for developing Nrf2 activators. Through extensive structure-activity relationship studies, we identified compound 56, which features a unique 5-tetrahydroisoquinoline scaffold and acts as a potent inhibitor of the Keap1-Nrf2 PPI. Compound 56 exhibited significant inhibitory activity (IC50 = 16.0 nM) and tight Keap1 binding affinity (Kd = 3.07 nM), along with acceptable oral bioavailability (F = 20%). Notably, 56 enhanced antioxidant defenses in HK-2 renal tubular epithelial cells and significantly reduced plasma creatinine and blood urea nitrogen levels in acute kidney injury (AKI) mice. These findings collectively position compound 56 as a promising candidate for the treatment of AKI.

7.
Kardiologiia ; 64(9): 87-95, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39392271

RESUMEN

AIM: Elevated levels of pro-inflammatory factors in plasma have been linked to worse prognosis after on-pump cardiac surgery, yet interventions that reduce the levels in patients have failed to improve prognosis. Therefore, we explored whether levels of pro-inflammatory factors are associated with prognosis of patients after valve surgery with cardiopulmonary bypass. MATERIAL AND METHODS: 244 patients were prospectively enrolled into observational study. Levels of tumor necrosis factor (TNF) - α, interleukin-8 and neutrophil elastase were measured once before and several times after cardiopulmonary bypass. The levels were compared between patients who experienced in-hospital adverse events or not, and between patients who experienced major adverse cardiac or cerebrovascular events (MACCEs) during three-year follow-up or not. RESULTS: Of the 244 patients enrolled, in-hospital adverse events occurred in 38 (15.6 %); of the 237 patients who completed follow-up, MACCEs occurred in 30 (12.7 %). Surgery led to significant increases in levels of all three pro-inflammatory factors, with levels returning to pre-bypass baseline on arrival in the intensive care unit (TNF-α), 4 h after arrival (interleukin-8) or 20 h after arrival (neutrophil elastase). However, pre- and post-bypass levels of all three factors did not differ significantly between patients who experienced adverse events in-hospital or not, or between patients who experienced MACCEs during follow-up or not. CONCLUSIONS: Levels of TNF-α, interleukin-8 and neutrophil elastase may not be associated with poor prognosis after cardiopulmonary bypass. This may help explain why "cytokine clearance" strategies fail to improve clinical outcomes after on-pump cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Interleucina-8 , Elastasa de Leucocito , Complicaciones Posoperatorias , Factor de Necrosis Tumoral alfa , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Pronóstico , Elastasa de Leucocito/sangre , Interleucina-8/sangre , Puente Cardiopulmonar/efectos adversos , Complicaciones Posoperatorias/sangre , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Anciano , Factor de Necrosis Tumoral alfa/sangre , Biomarcadores/sangre
8.
Mol Biomed ; 5(1): 46, 2024 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388072

RESUMEN

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.


Asunto(s)
Traumatismos por Radiación , Transducción de Señal , Células Madre , Humanos , Células Madre/efectos de la radiación , Células Madre/metabolismo , Animales , Traumatismos por Radiación/terapia , Traumatismos por Radiación/patología , Transducción de Señal/efectos de la radiación , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Enfermedades Intestinales/patología , Intestinos/efectos de la radiación , Intestinos/patología
9.
Mol Psychiatry ; 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39396064

RESUMEN

Emerging evidence supports the therapeutic potential of cannabinoids in Alzheimer's disease (AD), but the underlying mechanism upon how cannabinoids impact brain cognition and AD pathology remains unclear. Here we show that chronic cannabidiol (CBD) administration significantly mitigates cognitive deficiency and hippocampal ß-amyloid (Aß) pathology in 5×FAD mouse model of AD. CBD achieves its curative effect mainly through potentiating the function of inhibitory extrasynaptic glycine receptor (GlyR) in hippocampal dentate gyrus (DG). Based on the in vitro and in vivo electrophysiological recording and calcium imaging, CBD mediated anti-AD effects via GlyR are mainly accomplished by decreasing neuronal hyperactivity of granule cells in the DG of AD mice. Furthermore, the AAV-mediated ablation of DG GlyRα1, or the GlyRα1S296A mutation that exclusively disrupts CBD binding, significantly intercepts the anti-AD effect of CBD. These findings suggest a GlyR dependent mechanism underlying the therapeutic potential of CBD in the treatment of AD.

10.
Microsc Microanal ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39405407

RESUMEN

This comprehensive study delved into the detrimental effects of cadmium (Cd), a toxic heavy metal, on the testicular lamina propria (LP), a key player in spermatogenesis, and the maintenance of testicular stem cell niches. Utilizing transmission electron microscopy, immunohistochemistry, and double-labeling immunofluorescence, the research characterized the structural and cellular components of mouse testicular LP under Cd exposure and investigated the protective effects of quercetin. The findings illustrated that Cd exposure results in significant morphological and cellular modifications within the LP, including the apoptosis of peritubular myoid cells, an upsurge in CD34+ stromal cells displaying anti-apoptotic behaviors, and an excessive production of collagen Type I fibers and extracellular matrix. Remarkably, quercetin effectively counteracted these adverse changes by reversing apoptosis, reducing the proliferation of CD34+ stromal cells, and addressing fibrosis markers, thereby mitigating the cellular damage induced by Cd. This study not only highlighted the critical impact of apoptosis and fibrosis in Cd-related testicular damage but also elucidated the protective mechanism of quercetin, laying the groundwork for future clinical applications in addressing testicular damage from heavy metal poisoning through cellular therapeutics and pharmacological interventions.

11.
Angew Chem Int Ed Engl ; : e202413582, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39422656

RESUMEN

Hole transport materials (HTMs) are essential for improving the stability and efficiency of perovskite solar cells (PSCs). In this study, we have designed and synthesized a novel organic small molecule HTM, cor-(DPA)5, characterized by a bowl-shaped core with symmetric five diphenylamine groups. Compared to already-known HTMs, the bowl-shaped and relatively compact structure of cor-(DPA)5 facilitates intermolecular π-π interactions, promotes film formations, and enhances charge transport. Consequently, the cor-[DPA(2)]5 HTM exhibits high charge mobility, exceptional hydrophobicity, and a significantly elevated glass transition temperature. Superior to previously reported HTMs such as spiro-OMeTAD and cor-OMePTPA, our newly synthesized cor-(DPA)5 HTM is free from any ionic dopants. As a result, the dopant-free cor-[DPA(2)]5-based PSC demonstrates an impressive efficiency of 24.01%, and exhibits outstanding operational stability. It retains 96% after continuous exposure to 1 sun irradiation for 800 hours under MPP (maximum power point) tracking in ambient air. These findings present a structurally compact novel HTM and exemplify a new approach to the molecular design of HTM for the development of stable and effective PSCs.

12.
Respir Res ; 25(1): 376, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39420370

RESUMEN

Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients. Mechanistically, we found that upregulation of miR-1307-5p promoted TGF-ß induced lung fibroblast activation and transdifferentiation. We also identified FBXL16 as a direct target for miR-1307-5p mediated myofibroblast activation in COPD. Knockdown of FBXL16 by siRNA prominently increased the expression of myofibroblast markers in MRC-5 fibroblasts after TGF-ß administration. Ectopic expression of FBXL16 in MRC-5 counteracted miR-1307-5p agomir-induced fibroblast transdifferentiation. Furthermore, We found that miR-1307-5p promoted pulmonary fibroblast transdifferentiation through FBXL16 regulated HIF1α degradation. In general, our findings indicate that miR-1307-5p is important for COPD pathogenesis, and may serve as a potential target for COPD treatment.


Asunto(s)
Transdiferenciación Celular , Proteínas F-Box , Fibroblastos , Subunidad alfa del Factor 1 Inducible por Hipoxia , MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Animales , Femenino , Humanos , Masculino , Ratones , Células Cultivadas , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/biosíntesis , Fibroblastos/metabolismo , Fibroblastos/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , MicroARNs/metabolismo , MicroARNs/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/genética
13.
Oral Oncol ; 159: 107071, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39423549

RESUMEN

OBJECTIVES: To analyze the risk factors and explore effective treatments for epistaxis in nasopharyngeal carcinoma (NPC) patients. METHODS: From March 2006 to February 2020, 351 epistaxis patients visited our center and 195 patients meeting the inclusion criteria were enrolled in the study. Characteristics and treatments, including step-up hemostatic treatment (including medication, anterior ± posterior nostril packing, or further surgical hemostasis) and the CTPI emergency hemostasis method (including common carotid artery compression, tracheotomy / intubation, packing of nasal and nasopharynx, and interventional treatment), were analyzed. RESULTS: The median total bleeding volume was 100.0 ml (range 20-4430 ml). 126 (64.6 %) and 69 (35.4 %) patients suffered from non-massive epistaxis and massive epistaxis. The 1-year overall survival (OS) rate was 60.1 % for patients with massive epistaxis and 97.3 % for those with non-massive epistaxis treated with step-up hemostatic treatment. Among patients with massive epistaxis, the 1-year OS rate was 80.0 % for those who received CTPI and 13.3 % for those who received step-up hemostatic treatment. CONCLUSION: ICA exposure and hemostasis failure was adverse prognostic factors for OS in NPC patients with epistaxis. The step-up hemostatic treatment is effective for controlling non-massive epistaxis. The CTPI emergency method might be an effective hemostasis treatment for NPC patients with massive epistaxis, especially those with PRNN and ICA exposure.

14.
Diabetes Res Clin Pract ; : 111895, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39424147

RESUMEN

OBJECTIVE: This study aimed to assess the current state of self-monitoring of blood glucose (SMBG) in Chinese patients initiating premixed insulin and its influential factors. RESEARCH DESIGN AND METHODS: This is a single-arm, multi-center, prospective real-world study enrolling a total of 8214 adult patients with type 2 diabetes mellitus (T2DM) newly initiated premixed insulin analogues. Each patient was followed up for 12 weeks, and the data related to SMBG was collected at week 1, week 4, week 8 and week 12, while data related to glycated hemoglobin were collected at week 1 and week 12. The primary outcome was the frequency of SMBG over 12 weeks. RESULTS: At week 12, 83.3 % monitored blood glucose at least once, while 20.3 % of participants continued SMBG every week. The average monitoring frequency was 4.78 times/week over the first 4 weeks and 3.33 times/week over 12 weeks. The patients with a higher frequency of SMBG had better control of blood glucose. CONCLUSIONS: This study found that most T2DM patients would take SMBG but the adherence decreased over time. The adherence to SMBG in Chinese T2DM patients was influenced by age, insulin dosage, education level, and diabetes duration. SMBG benefited the improvement of glycemic control.

15.
BMC Ophthalmol ; 24(1): 449, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39407170

RESUMEN

BACKGROUND: We aimed to compare choroidal thickness (ChT) and retinal nerve fiber layer (RNFL) thickness in the affected and contralateral eyes of patients with Posner-Schlossman Syndrome (PSS) during acute, remission, and intermittent phases. METHODS: This prospective observational study included 18 patients(36 eyes) diagnosed with PSS. These patients underwent a comprehensive ophthalmologic evaluation including slit lamp examination, visual acuity testing, intraocular pressure (IOP) measurement, and funduscopic examination, and assessment of RNFL thickness, macular thickness, and macular ChT. Patient data collected included gender, age, number of keratic precipitates (KPs), and number of episodes. Optical coherence tomography (OCT) was used to measure RNFL thickness, macular thickness, and macular ChT in both eyes during the acute, remission, and intermittent phases. The affected eye was compared with the unaffected eye at each phase. RESULTS: In affected eyes, macular ChT was lower in the acute phase compared to the remission phase at N1500, N1000, N500, and subfoveal locations (allp < 0.05).The central macular recess ChT was also significantly thinner in the acute phase compared to the intermittent and remission phases. Age significantly correlated with ChT in the central recess (p = .024). Macular thickness was thinner during the acute phase in the affected eye (p = .048). The RNFL in the affected eye was thinner in the intermittent phase than in the acute phase at the inferior-temporal (p = .011) and global sectors (p = .044). During the acute phase, RNFL in the affected eye was thinner at the superior-nasal (p = .049), inferior-temporal (p = .003), and global (p = .041) sectors compared to the unaffected eye. In the intermittent phase, the affected eye's RNFL was thinner at the superior-nasal, inferior-temporal, inferior-nasal, and global sectors compared to the unaffected eye (allp < 0.05), while no difference was observed in both eyes at the nasal, superior-temporal, and temporal sectors. The number of episodes and age were significantly associated with RNFL thickness (p < .05). CONCLUSION: This study demonstrated that in eyes affected by PSS, RNFL, macular ChT, and macular thickness thinned during the acute phase. The number of episodes and age are significant factors in the development of PSS.


Asunto(s)
Coroides , Fibras Nerviosas , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Masculino , Femenino , Estudios Prospectivos , Coroides/patología , Coroides/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Adulto , Persona de Mediana Edad , Células Ganglionares de la Retina/patología , Agudeza Visual/fisiología , Fibras Nerviosas/patología , Presión Intraocular/fisiología , Adulto Joven , Retina/patología , Retina/diagnóstico por imagen
16.
Int J Mol Sci ; 25(19)2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39408586

RESUMEN

Iron redistribution in the intestine after total body irradiation is an established phenomenon. However, in the literature, there are no reports about the use of X-ray fluorescence microscopy or equivalent techniques to generate semi-quantitative 2D maps of iron in sectioned intestine samples from irradiated mice. In this work, we used X-ray fluorescence microscopy (XFM) to map the elemental content of iron as well as phosphorus, sulfur, calcium, copper and zinc in tissue sections of the small intestine from eight-week-old BALB/c male mice that developed gastrointestinal acute radiation syndrome (GI-ARS) in response to exposure to 8 Gray of gamma rays. Seven days after irradiation, we found that the majority of the iron is localized as hot spots in the intercellular regions of the area surrounding crypts and stretching between the outer perimeter of the intestine and the surface cell layer of villi. In addition, this study represents our current efforts to develop elemental cell classifiers that could be used for the automated generation of regions of interest for analyses of X-ray fluorescence maps. Once developed, such a tool will be instrumental for studies of effects of radiation and other toxicants on the elemental content in cells and tissues. While XFM studies cannot be conducted on living organisms, it is possible to envision future scenarios where XFM imaging of single cells sloughed from the human (or rodent) intestine could be used to follow up on the progression of GI-ARS.


Asunto(s)
Rayos gamma , Ratones Endogámicos BALB C , Microscopía Fluorescente , Animales , Rayos gamma/efectos adversos , Ratones , Masculino , Microscopía Fluorescente/métodos , Hierro/metabolismo , Hierro/análisis , Intestino Delgado/efectos de la radiación , Intestino Delgado/metabolismo , Intestinos/efectos de la radiación , Intestinos/patología , Espectrometría por Rayos X/métodos
17.
Front Oncol ; 14: 1361928, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39411129

RESUMEN

Giant cell glioblastoma often exhibits genome instability and is frequently associated with mutations in genes involved in DNA repair pathways including TP53 and DNA mismatch repair genes. Several germline mutations have been identified in giant cell glioblastoma, including mutations of MSH1 and MSH2, TP53, and POLE. We have documented a case of a germline mutation in CHEK2, another gene crucial to DNA repair, in a patient with giant cell glioblastoma. The CHEK2 mutation was inherited from the patient's father, who had a history of gastric cancer and renal cell carcinoma. In addition to the germline CHEK2 mutation, the giant cell glioblastoma exhibited a genome-wide loss of heterozygosity, a characteristic observed in a subset of giant cell glioblastomas. Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

18.
Food Chem ; 464(Pt 2): 141715, 2024 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-39442220

RESUMEN

Revealing the interaction modes between nanoscale metal-organic frameworks (NMOFs) and food matrix is crucial for functional release but it still remains largely unknown to date. This study specifically focused on the milk protein adsorption mechanism of NMOFs using UiO66/UiO66-NH2 and ß-lactoglobulin (ß-LG) as models. UiO66 and UiO66-NH2 quenched the fluorescence of ß-LG via static mechanism. Due to the enhanced electrostatic forces caused by NH2, UiO66-NH2-ß-LG (2.83 × 105 mol·L-1) exhibited higher binding constant than UiO66-ß-LG (2.61 × 105 mol·L-1), while UiO66 with higher hydrophobicity adsorbed more ß-LG. The defects of UiO influenced the binding sites on the ß-LG, and the higher the defect degree, the higher the binding energy. For the stability of the system, the H-bonding between UiO66 and SER30/PRO38, and the hydrophobic interaction between UiO66-NH2 and LYS101 played important roles. Furthermore, the secondary structure content of ß-LG changed after interacting with both UiO, resulting in reduced density of ß-LG.

19.
ACS Appl Mater Interfaces ; 16(42): 56850-56861, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39380427

RESUMEN

The azobenzene moiety is an intriguing structure that deforms under UV and visible light, indicating a high potential for biomedical applications. However, its reaction to UV radiation is problematic because of its high energy and low tissue penetration. Unlike previous research on azobenzene structures in photoresponsive materials, this study presents a novel method for imparting photostimulation-responsive properties to liposomes by incorporating the azobenzene moiety and extending the light wavelength with up-conversion nanoparticles. First, the azobenzene structure was incorporated into a phospholipid molecule to create Azo-PSG, which could spontaneously form vesicle assemblies in aqueous solutions and isomerizes within 1 h of light exposure. Furthermore, orthogonal up-conversion nanoparticles with a core-shell structure were created by sequentially growing lanthanide rare earths in the shell layer, which efficiently converts near-infrared light into ultraviolet (400 nm) and blue-green (540 nm) light. Combining these core-shell structured up-conversion nanomaterials with Azo-PSG molecules resulted in the creation of a near-infrared light-responsive smart nanoliposome system. Under near-infrared light irradiation, UCNPs emit UV and blue-green light, causing conformational changes in Azo-PSG molecules that allow drug release within 6 h. The reversible structural shift of Azo-PSG in response to light stimulation holds enormous promise for improving drug release techniques. This novel technique also expands the usage of UV-responsive compounds beyond their constraints of low penetration and high biotoxicity, allowing for rapid medication release under NIR light.


Asunto(s)
Compuestos Azo , Liberación de Fármacos , Rayos Infrarrojos , Liposomas , Nanopartículas , Compuestos Azo/química , Compuestos Azo/efectos de la radiación , Liposomas/química , Nanopartículas/química , Preparaciones de Acción Retardada/química , Humanos , Rayos Ultravioleta
20.
Sci Rep ; 14(1): 24638, 2024 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-39428424

RESUMEN

To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart Dmean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI.


Asunto(s)
Contencion de la Respiración , Tomografía Computarizada de Haz Cónico , Estudios de Factibilidad , Mastectomía , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada , Neoplasias de Mama Unilaterales , Humanos , Femenino , Radioterapia de Intensidad Modulada/métodos , Neoplasias de Mama Unilaterales/radioterapia , Neoplasias de Mama Unilaterales/cirugía , Neoplasias de Mama Unilaterales/diagnóstico por imagen , Persona de Mediana Edad , Planificación de la Radioterapia Asistida por Computador/métodos , Anciano , Adulto , Radiometría , Inhalación , Pulmón/efectos de la radiación , Pulmón/diagnóstico por imagen , Estudios Prospectivos , Corazón/efectos de la radiación , Corazón/diagnóstico por imagen
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