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Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re-epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu-TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu-TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5-fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co-delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu-TSs not only promote macrophage phenotype-switching to inhibit inflammation by interleukin-related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen-related pathways. Therefore, TA/Fu-TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype-switching and anti-fibrosis effect.
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Cicatriz Hipertrófica , Humanos , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Nanogeles/uso terapéutico , Fibrosis , Fenotipo , Triamcinolona Acetonida/uso terapéutico , Fluorouracilo/uso terapéutico , Inflamación , Macrófagos/metabolismoRESUMEN
Surgical scar formation afflicts patients and current treatments are limited by inconsistent efficacy, long-term and painful treatment processes. In this report, a patient received 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA PDT) on the first postoperative day, once a week for 5 sessions. At two-year follow-up, the intervention of 5-ALA PDT at early stage decreased the vascular density and improved extracellular matrix (ECM) deposition. The early intervention of surgical scar by 5-ALA PDT overcomes the penetration limits of photosensitizer and red light, making it a potential strategy for surgical scar prevention.
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Ácido Aminolevulínico , Fotoquimioterapia , Humanos , Ácido Aminolevulínico/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Cicatriz/tratamiento farmacológico , Cicatriz/etiología , Fotoquimioterapia/métodos , Luz RojaRESUMEN
Rhythm control is the core part of the integrated management of atrial fibrillation (AF), especially in the early stages. Despite advances in catheter ablation (CA), the recurrence rate of AF after CA remains high. As a result, stratification and early management of AF recurrence after CA are critical. Currently, predictors of recurrence of AF after CA are mostly based on dysfunction caused by structural remodeling, apart from traditional risk factors. Atrial strain is a recently developed important parameter for detecting the deformability of atrial myocardium during the cardiac cycle prior to atrial remodeling. Although there is only preliminary evidence, atrial strain is still a promising parameter in predicting the recurrence of AF after CA at an early stage. This review focuses on the evaluation of atrial strain, the current applications of atrial strain in assessing atrial function, and predicting the recurrence of AF after CA. We summarize the contents related as follows: (1) CA for rhythm control in AF; (2) Evaluation methods of atrial strain; (3) Atrial strain in the remodeling and reverse remodeling of AF; and (4) Clinical applications of atrial strain in predicting the recurrence of AF after CA. Although there is accumulating evidence on the role of decreased atrial strain in the early prediction of AF recurrence, atrial strain is limited in clinical practice for lacking exact cut-off values and difficulty in distinguishing specific function phases of the atrium. More research is needed in the future to add strength to the early prediction value of atrial strain in AF recurrences.
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Background: Hypertrophic scars (HS) represent one of the most common clinical challenges due to unsatisfactory therapeutic results. HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior. Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation. This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation. Methods: Here, augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts (HFs) and HS tissues, and the suppression of glycolysis also attenuated fibroblast activation. We also introduced IR780, a heptamethine cyanine dye, to regulate glycolysis for the control of HS formation. Results: In vitro, cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs. In vivo, the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation. Furthermore, IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies, and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts. Conclusions: This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.
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Background: Hypertrophic scar formation may be related to cutaneous neurogenic inflammation (CNI) through the substance P-neurokinin 1 receptor (SP-NK1R) signaling pathway. As a widely used drug in aesthetic clinical work, botulinum toxin type A (BTX-A) has a therapeutic effect on scars, but the actual mechanism remains unclear. This study aimed to clarify the potential mechanism by which BTX-A inhibits CNI in hypertrophic scars both in vitro and in vivo. Methods: Tissue samples were obtained from surgical excisions. Immunohistological analysis was used to locate SP in human hypertrophic scars and normal skin. RT-PCR and western blot analysis were used to evaluate the expression of collagens after SP/BTX-A treatment. A rabbit ear scar model was used to explore the in vivo effect of BTX-A on scar treatment. Results: SP and NK-1R were overexpressed in hypertrophic scars compared to normal skin tissues. Collagen secretion of hypertrophic scar-derived fibroblasts increased with increasing doses of SP. However, BTX-A may downregulate collagen expression through SP-NK1R pathway with or without the presence of SP inducing agent capsaicin. Meanwhile, SP inhibited the expression of NK-1R, and this inhibition was blocked by pretreatment with BTX-A. In vivo, intralesional BTX-A injection can also reduce the volume of scars and inhibit collagen secretion. Capsaicin may cause more severe scar manifestations, while the therapeutic effect of BTX-A remains. Conclusion: Our research confirms that CNI stimulates fibroblasts during scar formation, while BTX-A can reduce collagen secretion by inhibiting the SP-NK1R signaling pathway, thus identifying a novel therapeutic target for this benign solid skin tumor.
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BACKGROUND: Myocardial Ischemia with No Obstructive Coronary Artery Disease (MINOCA) is a common cause of type 2 acute myocardial infarction (AMI) which requires careful differential diagnosis. Coronary artery spasm (CAS) syndrome is one etiology that can lead to MINOCA. Nilotinib, a targeted treatment for chronic myeloid leukemia (CML), has been reported to be related with increased risk of adverse vascular events. CASE PRESENTATION: A 67-year-old male patient was admitted to hospital with acute chest pain. He had a past medical history of CML and a history of treatment with nilotinib for 12 months. Coronary angiography (CAG) showed no significant stenosis. Since the onset of angina was generally in the early morning, and ECG and echocardiography suggested right coronary artery (RCA) disease, an ergonovine provocation test was performed to confirm the diagnosis of CAS. After intracoronary administration of ergonovine, middle and distal RCA showed over 90% vasoconstriction. Nilotinib related MINOCA, CAS and CML were diagnosed. Lifestyle changes (cessation of smoking), anti-spasmodics, statin treatment and adjustment of the nilotinib dose (from 200 mg bid, to 150 mg bid) were recommended for this patient. Six-month's follow-up showed good recovery with no onsets of angina. CONCLUSIONS: Physicians should be vigilant to adverse vascular events when treating patients who have been prescribed nilotinib. It is suggested that in patients with MINOCA who have a history of treatment with nilotinib, CAS-induced MINOCA should be included in the differential diagnosis. Further studies are needed to clarify the mechanism and to find better management.
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Antineoplásicos/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , MINOCA/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Anciano , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , MINOCA/diagnóstico por imagen , MINOCA/terapia , Masculino , Cese del Hábito de Fumar , Resultado del Tratamiento , Vasodilatadores/uso terapéuticoRESUMEN
Synergistic transdermal photodynamic therapy (PDT)/photothermal therapy (PTT) has emerged as a novel strategy for improving hypertrophic scar (HS) therapeutic outcomes. Herein, a near-infrared heptamethine cyanine dye, named IR-808, has been selected as the desirable photosensitizer owing to its PDT and PTT properties. Benefitting from the transdermal delivery ability of ethosomes (ESs), IR-808 loaded nanoethosomes (IR-808-ES) have been prepared as a novel nanophotosensitizer for the transdermal PDT/PTT of HSs. The special structure of IR-808 aggregate distribution in the ES lipid membrane enhances ROS generation and hyperthermia. The in vitro experiments indicate that the IR-808-ES enhances the PDT/PTT efficacy for inducing the HS fibroblast (HSF) apoptosis via the intrinsic mitochondrial pathway. Furthermore, the in vivo transdermal delivery studies reveal that the IR-808-ES efficiently delivers IR-808 into HSFs in the HS tissue. Systematic assessments in the rabbit ear HS models demonstrate that the enhanced PDT/PTT performance of the IR-808-ES has remarkable therapeutic effects on improving the HS appearance, promoting HSF apoptosis and remodeling collagen fibers. Therefore, the IR-808-ES integrates both the transdermal delivery ability and the aggregation-enhanced PDT/PTT effect, and these features endow the IR-808-ES with significant potential as a novel nanophotosensitizer for the transdermal phototherapy of HSs in the clinical field.
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Cicatriz Hipertrófica , Hipertermia Inducida , Fotoquimioterapia , Animales , Carbocianinas , Cicatriz Hipertrófica/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , ConejosRESUMEN
BACKGROUND: Due to its low incidence and diverse manifestations, paradoxical embolism (PDE) is still under-reported and is not routinely considered in differential diagnoses. Concomitant acute myocardial infarction (AMI) and acute pulmonary embolism (PE) caused by PDE has rarely been reported. CASE PRESENTATION: A 45-year-old woman presented with acute chest pain and difficulty with breathing. Multiple imaging modules including ECG, echocardiography, emergency cardioangiogram (CAG), and CT angiography of the pulmonary arteries showed acute occlusion of the posterolateral artery and acute PE. After coronary aspiration, no residual stenosis was observed. One month later, a bubble study showed inter-atrial communication via a patent foramen ovale (PFO). The AMI in this patient was finally attributed to PDE via the PFO. PFO closure was performed, and long-term anticoagulation was prescribed to prevent recurrent thromboembolic events. CONCLUSIONS: PDE via PFO is a rare etiology of AMI, especially in patients with concomitant AMI and PE. Clinicians should be vigilant of this possibility and close the inter-atrial channel for secondary prevention.
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Embolia Paradójica/etiología , Foramen Oval Permeable/complicaciones , Infarto de la Pared Inferior del Miocardio/etiología , Embolia Pulmonar/etiología , Infarto del Miocardio con Elevación del ST/etiología , Anticoagulantes/uso terapéutico , Embolia Paradójica/diagnóstico por imagen , Embolia Paradójica/prevención & control , Femenino , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/terapia , Humanos , Infarto de la Pared Inferior del Miocardio/diagnóstico por imagen , Infarto de la Pared Inferior del Miocardio/prevención & control , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/prevención & control , Recurrencia , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/prevención & control , Prevención Secundaria , Resultado del TratamientoRESUMEN
Transdermal drug delivery system (TDDS) is an attractive method for drug delivery with convenient application, less first-pass effect, and fewer systemic side effects. Among all generations of TDDS, transdermal nanocarriers show the greatest clinical potential because of their non-invasive properties and high drug delivery efficiency. However, it is still difficult to design optimal transdermal nanocarriers to overcome the skin barrier, control drug release, and achieve targeting. Hence, surface modification becomes a promising strategy to optimize and functionalize the transdermal nanocarriers with enhanced penetration efficiency, controlled drug release profile, and targeting drug delivery. Therefore, this review summarizes the developed transdermal nanocarriers with their transdermal mechanism, and focuses on the surface modification strategies via their different functions.
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Portadores de Fármacos , Nanopartículas/administración & dosificación , Administración Cutánea , Animales , Propiedades de SuperficieRESUMEN
Cutaneous melanoma is one of the most common malignancies with increased incidence in the past few decades, making it a significant public health problem. The early diagnosis of melanoma is a major factor in improving patient's survival. The traditional pathway to melanoma diagnosis starts with a visual diagnosis, followed by subsequent biopsy and histopathologic evaluation. Recently, multiple innovative optical technology-based methods, including dermoscopy, reflectance confocal microscopy, optical coherence tomography, multiphoton excited fluorescence imaging and stepwise two-photon excited fluorescence (dermatofluoroscopy), have been developed to increase the diagnostic accuracy for the non-invasive melanoma diagnosis. Some of them have already been applied to real-life clinical settings, others require more research and development. These technologies show promise in facilitating the diagnosis of melanoma since they are non-invasive, sensitive, objective and easy to apply. Diagnostic accuracy, detection time, portability and the cost-effectiveness of the device are all aspects that need to be improved. This article reviews the method of these emerging optical non-invasive diagnostic technologies, their clinical application, their benefits and limitations, as well as their possible future development.
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Melanoma , Fotoquimioterapia , Neoplasias Cutáneas , Dermoscopía , Humanos , Melanoma/diagnóstico por imagen , Microscopía Confocal , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Neoplasias Cutáneas/diagnóstico por imagen , Tomografía de Coherencia ÓpticaRESUMEN
Photodynamic therapy (PDT) is a new therapeutic strategy for hypertrophic scars (HSs), and nanoethosomes (ES) have attracted considerable attention as an efficient transdermal delivery system for PDT of HSs (HS-PDT). However, the delivery of photosensitizers and the hypoxic microenvironment of HSs limit HS-PDT efficacy. Consequently, functional transdermal ES (A/A-ES) that are loaded with the photosensitizer, 5-aminolevulinic acid (ALA), and immobilized nanoenzyme Au nanoclusters (ANCs) within the ES surface have been developed that exhibit superior co-delivery characteristics and produce catalase that enhances HS-PDT efficacy. The unique structure of A/A-ES enables them to co-deliver ALA and ANCs into the HS tissue and to efficiently decompose the endogenous hydrogen peroxide in the HS to generate oxygen. The findings from in vitro and in vivo experiments demonstrated that A/A-ES efficiently co-delivered ALA and ANCs into the HS tissue and that they improved the hypoxic microenvironment of the HS. Systematic assessments reveal that A/A-ES enhance HS-PDT efficacy and that they are highly effective at improving the morphology and promoting HS fibroblast apoptosis and the rearrangement of collagen. These works give rise to an effective treatment option for HSs that integrates the transdermal co-delivery of ALA and nanoenzymes, thereby enabling them to exert their respective beneficial effects, and they highlight the enhancement of HS-PDT efficacy via self-generating oxygen.
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Ácido Aminolevulínico/farmacología , Cicatriz Hipertrófica/tratamiento farmacológico , Oro/farmacología , Nanopartículas/química , Oxígeno/metabolismo , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Ácido Aminolevulínico/química , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Sistemas de Liberación de Medicamentos , Oro/química , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/metabolismo , Tamaño de la Partícula , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Conejos , Propiedades de SuperficieAsunto(s)
Trastornos de Ansiedad/epidemiología , Infecciones por Coronavirus/epidemiología , Trastorno Depresivo/epidemiología , Personal de Salud/estadística & datos numéricos , Neumonía Viral/epidemiología , Cuarentena/estadística & datos numéricos , Adulto , Ansiedad/epidemiología , Ansiedad/psicología , Trastornos de Ansiedad/psicología , Betacoronavirus , COVID-19 , Estudios de Casos y Controles , China/epidemiología , Depresión/epidemiología , Depresión/psicología , Trastorno Depresivo/psicología , Femenino , Personal de Salud/psicología , Humanos , Modelos Logísticos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Aplicaciones Móviles , Pandemias , Cuestionario de Salud del Paciente , Prevalencia , Cuarentena/psicología , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
We synthesized a generation of water-soluble, atomically precise gold nanoclusters (Au NCs) with anisotropic surface containing a short dithiol pegylated chain (AuMHA/TDT). The AuMHA/TDT exhibit a high brightness (QY â¼ 6%) in the shortwave infrared (SWIR) spectrum with a detection above 1250 nm. Furthermore, they show an extended half-life in blood (t1/2ß = 19.54 ± 0.05 h) and a very weak accumulation in organs. We also developed a non-invasive, whole-body vascular imaging system in the SWIR window with high-resolution, benefiting from a series of Monte Carlo image processing. The imaging process enabled to improve contrast by 1 order of magnitude and enhance the spatial resolution by 59%. After systemic administration of these nanoprobes in mice, we can quantify vessel complexity in depth (>4 mm), allowing to detect very subtle vascular disorders non-invasively in bone morphogenetic protein 9 (Bmp9)-deficient mice. The combination of these anisotropic surface charged Au NCs plus an improved SWIR imaging device allows a precise mapping at high-resolution and an in depth understanding of the organization of the vascular network in live animals.
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Oro , Ondas de Radio , Animales , Diagnóstico por Imagen , Luz , Ratones , AguaRESUMEN
As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70µg/15ml or 350µg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70µg/15ml) or budesonide (250µg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.