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1.
Bioact Mater ; 42: 257-269, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39285913

RESUMEN

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

2.
ACS Biomater Sci Eng ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255244

RESUMEN

Mussel refers to a marine organism with strong adhesive properties, and it secretes mussel adhesion protein (MAP). The most vital feature of MAP is the abundance of the 3,4-dihydroxyphenylalanine (DOPA) group and lysine, which have antimicrobial, anti-inflammatory, antioxidant, and cell adhesion-promoting properties and can accelerate wound healing. Polydopamine (PDA) is currently the most widely used mussel-inspired material characterized by good adhesion, biocompatibility, and biodegradability. It can mediate various interactions to form functional coatings on cell-material surfaces. Nanofibers based on MAP and mussel-inspired materials have been exerting a vital role in wound repair, while there is no comprehensive review presenting them. This Review introduces the structure of MAPs and their adhesion mechanisms and mussel-inspired materials. Second, it introduces the functionalized modification of MAPs and their inspired materials in electrospun nanofibers and application in wound repair. Finally, the future development direction and coping strategies of MAP and mussel-inspired materials are discussed. Moreover, this Review can offer novel strategies for the application of nanofibers in wound repair and bring about new breakthroughs and innovations in tissue engineering and regenerative medicine.

4.
Sci Rep ; 14(1): 19526, 2024 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174669

RESUMEN

Early postoperative cerebral infarction (ePCI) is a serious complication of spontaneous intracerebral hemorrhage (SICH). Yet, no study has specifically focused on ePCI among SICH patients. Our study aims to investigate the characteristics, predictors, and outcomes of ePCI observed on computed tomography (CT) within 72 h after surgery in patients with supratentorial SICH. Data from a single-center SICH study conducted from May 2015 to September 2022 were retrospectively analyzed. We described the characteristics of ePCI. Predictors were identified through logistic regression analysis, and the impact of ePCI on six-month mortality was examined using a Cox regression model. Subgroup analyses and the "E-value" approach assessed the robustness of the association between ePCI and mortality. A retrospective analysis of 637 out of 3938 SICH patients found that 71 cases (11.1%) developed ePCI. The majority of ePCI cases occurred on the bleeding side (40/71, 56.3%) and affected the middle cerebral artery (MCA) territory (45/71, 63.4%). Multivariable analysis showed that the Glasgow Coma Scale (GCS) score (odds ratio (OR), 0.62; 95% CI, 0.48-0.8; p < 0.001), bleeding volume (per 100 ml) (OR, 1.17; 95% CI, 1.03-1.32; p = 0.016), hematoma volume (per 10 ml) (OR, 1.14; 95%CI, 1.02-1.28; p = 0.023) and bilateral brain hernia (OR, 6.48; 95%CI, 1.71-24.48; p = 0.006) independently predicted ePCI occurrence. ePCI was significantly associated with increased mortality (adjusted hazard ratio (HR), 3.6; 95% CI, 2.2-5.88; p < 0.001). Subgroup analysis and E-value analysis (3.82-6.66) confirmed the stability of the association. ePCI is a common complication of SICH and can be predicted by low GCS score, significant bleeding, large hematoma volume, and brain hernia. Given its significant increase in mortality, ePCI should be explored in future studies.


Asunto(s)
Hemorragia Cerebral , Infarto Cerebral , Complicaciones Posoperatorias , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Hemorragia Cerebral/mortalidad , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Infarto Cerebral/mortalidad , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Escala de Coma de Glasgow
5.
Int J Biol Macromol ; 278(Pt 1): 134673, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142491

RESUMEN

Charcot-Marie-Tooth type 2A (CMT2A) is a single-gene motor sensory neuropathy caused by Mfn2 mutation. It is generally believed that CMT2A involves mitochondrial fusion disruption. However, how Mfn2 mutation mediates the mitochondrial membrane fusion loss and its further pathogenic mechanisms remain unclear. Here, in vivo and in vitro mouse models harboring the Mfn2R364W, Mfn2G176S and Mfn2H165R mutations were constructed. Mitochondrial membrane fusion and fission proteins analysis showed that Mfn2R364W, Mfn2G176S, and Mfn2H165R/+ mutations maintain the expression of Mfn2, but promote Drp1 upregulation and Opa1 hydrolytic cleavage. In Mfn2H165R/H165R mutation, Mfn2, Drp1, and Opa1 all play a role in inducing mitochondrial fragmentation, and the mitochondrial aggregation is affected by Mfn2 loss. Further research into the pathogenesis of CMT2A showed these three mutations all induce mitochondria-mediated apoptosis, and mitochondrial oxidative phosphorylation damage. Overall, loss of overall fusion activity affects mitochondrial DNA (mtDNA) stability and causes mitochondrial loss and dysfunction, ultimately leading to CMT2A disease. Interestingly, the differences in the pathogenesis of CMT2A between Mfn2R364W, Mfn2G176S, Mfn2H165R/+ and Mfn2H165R/H165R mutations, including the distribution of Mfn2 and mitochondria, the expression of mitochondrial outer membrane-associated proteins (Bax, VDAC1 and AIF), and the enzyme activity of mitochondrial complex I, are related to the expression of Mfn2.


Asunto(s)
Apoptosis , Enfermedad de Charcot-Marie-Tooth , GTP Fosfohidrolasas , Mitocondrias , Mutación , Fosforilación Oxidativa , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedad de Charcot-Marie-Tooth/patología , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/genética , Ratones , Apoptosis/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Dinámicas Mitocondriales/genética , Humanos , Modelos Animales de Enfermedad
6.
ESC Heart Fail ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700133

RESUMEN

AIMS: Electronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI-powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients. METHODS AND RESULTS: We used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population). We implemented a keyword search strategy complemented by filtering based on International Classification of Diseases (ICD) codes and prescription data to EHR data set. We then applied DL for the automated interpretation of echocardiographic DICOM images. These methods were then integrated with the analysis of routinely stored plasma samples to identify and categorize patients into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and controls without HF. The final diagnosis was verified through a manual review of medical records, measured natriuretic peptides in stored blood samples, and by comparing clinical outcomes among groups. In our study, we selected the patient cohort through an algorithmic workflow. This process started with 60 850 EHR data and resulted in a final cohort of 578 patients, divided into 186 controls, 236 with HFpEF, and 156 with HFrEF, after excluding individuals with mismatched data or significant valvular heart disease. The analysis of baseline characteristics revealed that compared with controls, patients with HFrEF and HFpEF were generally older, had higher BMI, and showed a greater prevalence of co-morbidities such as diabetes, COPD, and CKD. Echocardiographic analysis, enhanced by DL, provided high coverage, and detailed insights into cardiac function, showing significant differences in parameters such as left ventricular diameter, ejection fraction, and myocardial strain among the groups. Clinical outcomes highlighted a higher risk of hospitalization and mortality for HF patients compared with controls, with particularly elevated risk ratios for both HFrEF and HFpEF groups. The concordance between the algorithmic selection of patients and manual validation demonstrated high accuracy, supporting the effectiveness of our approach in identifying and classifying HF subtypes, which could significantly impact future HF diagnosis and management strategies. CONCLUSIONS: Our study highlights the feasibility of combining keyword searches in EHR, DL automated echocardiographic interpretation, and biobank resources to identify HF subtypes.

7.
J Funct Biomater ; 15(4)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38667559

RESUMEN

The dermal-epidermal junction (DEJ), located between the dermal-epidermal layers in human skin tissue, plays a significant role in its function. However, the limitations of biomaterial properties and microstructure fabrication methods mean that most current tissue engineered skin models do not consider the existence of DEJ. In this study, a nanofiber membrane that simulates the fluctuating structure of skin DEJ was prepared by the composite molding process. Electrospinning is a technique for the production of nanofibers, which can customize the physical and biological properties of biomaterials. At present, electrospinning technology is widely used in the simulation of customized natural skin DEJ. In this study, four different concentration ratios of poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanofiber membranes were prepared based on electrospinning technology. We selected a 15%PLGA + 5%PCL nanofiber membrane with mechanical properties, dimensional stability, hydrophilicity, and biocompatibility after physical properties and biological characterization. Then, the array-based microstructure model was prepared by three-dimensional (3D) printing. Subsequently, the microstructure was created on a 15%PLGA + 5%PCL membrane by the micro-imprinting process. Finally, the cell proliferation and live/dead tests of keratinocytes (HaCaTs) and fibroblasts (HSFs) were measured on the microstructural membrane and flat membrane. The results showed that 15%PLGA + 5%PCL microstructure membrane was more beneficial to promote the adhesion and proliferation of HaCaTs and HSFs than a flat membrane.

8.
ACS Biomater Sci Eng ; 10(5): 2805-2826, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38621173

RESUMEN

Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.


Asunto(s)
Polivinilos , Ingeniería de Tejidos , Andamios del Tejido , Polivinilos/química , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Humanos , Impresión Tridimensional , Materiales Biocompatibles/química , Polímeros/química , Animales , Polímeros de Fluorocarbono
9.
J Neurotrauma ; 41(15-16): e2009-e2025, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38553903

RESUMEN

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-ß. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent tracer migration from MLVs to deep cervical lymph nodes (dCLNs). Remarkably, CBD treatment also induced a reversion in aquaporin-4 (AQP-4) polarization and curtailed neuroinflammatory indices. A pivotal discovery was that the surgical interruption of efferent lymphatic conduits in the neck nullified CBD's positive contributions to intracranial waste disposal and cognitive improvement, yet the anti-neuroinflammatory actions remained unaffected. These insights suggest that CBD may enhance intracranial metabolite clearance, potentially via the regulation of the intracranial lymphatic system, thereby offering neurofunctional prognostic improvement in TBI models. Our findings underscore the potential therapeutic applicability of CBD in TBI interventions, necessitating further comprehensive investigations and clinical validations to substantiate these initial conclusions.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Cannabidiol , Sistema Glinfático , Ratones Endogámicos C57BL , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Animales , Ratones , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Masculino , Sistema Glinfático/efectos de los fármacos , Sistema Glinfático/metabolismo , Vasos Linfáticos/efectos de los fármacos
10.
CNS Neurosci Ther ; 30(3): e14673, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38468459

RESUMEN

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.


Asunto(s)
Edema Encefálico , Lesiones Traumáticas del Encéfalo , Vasos Linfáticos , Humanos , Animales , Edema Encefálico/patología , Linfocitos T , Lesiones Traumáticas del Encéfalo/patología , Encéfalo/patología , Apoptosis , Citocinas , Vasos Linfáticos/patología , Linfocitos T CD4-Positivos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Modelos Animales de Enfermedad
11.
Biofabrication ; 16(2)2024 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-38306682

RESUMEN

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.


Asunto(s)
Biomimética , Células Epidérmicas , Epidermis/patología , Queratinocitos , Piel , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
12.
Sci Rep ; 14(1): 3559, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347043

RESUMEN

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.


Asunto(s)
Hematoma Subdural Crónico , Humanos , Estudios Retrospectivos , Atorvastatina/uso terapéutico , Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Dexametasona/uso terapéutico
13.
Chin Neurosurg J ; 10(1): 4, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273380

RESUMEN

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

14.
Ultramicroscopy ; 258: 113922, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38217895

RESUMEN

The contrast transfer function of direct ptychography methods such as the single side band (SSB) method are single signed, yet these methods still sometimes exhibit contrast reversals, most often where the projected potentials are strong. In thicker samples central focusing often provides the best ptychographic contrast as this leads to defocus variations within the sample canceling out. However focusing away from the entrance surface is often undesirable as this degrades the annular dark field (ADF) signal. Here we discuss how phase wrap asymptotes in the frequency response of SSB ptychography give rise to contrast reversals, without the need for dynamical scattering, and how these can be counteracted by manipulating the phases such that the asymptotes are either shifted to higher frequencies or damped via amplitude modulation. This is what enables post collection defocus correction of contrast reversals. However, the phase offset method of counteracting contrast reversals we introduce here is generally found to be superior to post collection application of defocus, with greater reliability and generally stronger contrast. Importantly, the phase offset method also works for thin and thick samples where central focusing does not. Finally, the independence of the method from focus is useful for optical sectioning involving ptychography, improving interpretability by better disentangling the effects of strong potentials and focus.

15.
J Neurotrauma ; 41(5-6): 660-670, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38204204

RESUMEN

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Imidazoles , Receptor de Angiotensina Tipo 2 , Sulfonamidas , Tiofenos , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Volumen Sistólico , Función Ventricular Izquierda , Encéfalo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Citocinas
16.
Theranostics ; 14(1): 304-323, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38164141

RESUMEN

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.


Asunto(s)
Sistema Glinfático , Vasos Linfáticos , Ratas , Animales , Atorvastatina/farmacología , Células Endoteliales , Sistema de Señalización de MAP Quinasas , Hematoma Subdural
17.
Mol Cell Biochem ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294731

RESUMEN

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

18.
Plant Dis ; : PDIS07231369RE, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-37822099

RESUMEN

Black point, a severe global wheat disease, necessitates deploying resistant cultivars for effective control. However, susceptibility remains prevalent among most wheat cultivars. Identifying new sources of resistance and understanding their mechanisms are crucial for breeding resistant cultivars. This study pinpointed black point resistance in an ethyl methane sulfonate (EMS)-mutagenized wheat population of Wanyuanbai 1 (WYB) and analyzed resistant mutants using RNA-Seq. The findings revealed the following: (i) wyb-18, among 10,008 EMS-mutagenized lines, exhibited robust resistance with significantly lower black point incidence under artificial Bipolaris sorokiniana inoculation in 2020 and 2021 (average incidence of 5.2% over 2 years), markedly reduced compared with WYB (50.9%). (ii) wyb-18 kernels displayed black point symptoms at 12 days after inoculation (dai), 3 days later than WYB. At 15 dai, wyb-18 kernels had isolated black spots, unlike WYB kernels, where the entire embryo turned black. (iii) wyb-18 showed heightened antioxidant enzyme activity, including peroxidase, catalase, and superoxide dismutase. (iv) Analysis of 543 differentially expressed genes between wyb-18 and WYB at 9 dai identified enrichment in the MAPK signaling pathway through KEGG analysis. Ten genes in this pathway exhibited upregulated expression, while one was downregulated in wyb-18. Among these genes, PR1, WRKY11, SAPK5, and TraesCS1A02G326800 (chitin recognition protein) consistently showed upregulation in wyb-18, making them potential candidates for black point resistance. These results offer valuable germplasm resources for breeding and novel insights into the mechanisms of black point resistance.

19.
APL Bioeng ; 7(4): 046119, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38075208

RESUMEN

Skin lesions not only disrupt appearance and barrier functionality but also lead to severe microbial infections and immune-inflammatory responses, seriously affect physical and mental health. In situ printing involves the direct deposition of bio-ink to create or repair damaged tissues or organs within a clinical setting. In this study, we designed and fabricated a novel portable in situ printer. This handheld instrument exhibits excellent printing performance, allowing hydrogels to be patterned and molded on surfaces according to specific requirements. By utilizing a dual-component hydrogels co-printing approach with high and low viscosities, we achieved in situ cell-laden printing using low-viscosity hydrogel. This demonstrates the advantages of the device in maintaining cell viability and achieving hydrogel structuring. This approach opens up the possibilities for the efficient encapsulation of active components such as drugs, proteins, and cells, enabling controlled macro- and micro-structuring of hydrogels. This breakthrough finding highlights the potential of our technical approach in dermatological treatment and wound repair, by dynamically adapting and regulating microenvironments in conjunction with hydrogel scaffolds and cell reparative impetus.

20.
Heliyon ; 9(11): e21854, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38058607

RESUMEN

The effects of different processing methods on the nutritional components of sea cucumber (Apostichopus japonicus) are of concern to consumers who select sea cucumber products. This study employed liquid chromatography tandem mass spectrometry to examine the metabolites in fresh, unsoaked salted, soaked salted, and instant sea cucumber body wall samples sourced from Dalian, China. Metabolites were evaluated utilizing partial least squares discriminant analysis (PLS-DA) and subsequently subjected to KEGG metabolic pathway analysis for further investigation. PLS-DA effectively discriminated the body wall metabolites of sea cucumbers obtained via various processing techniques. The differential metabolites identified predominantly encompassed amino acids, lipids, and carbohydrates. Subsequent KEGG metabolic pathway analysis demonstrated a significant association between lipid, carbohydrate, and amino acid metabolism and the specific processing methods employed. The assessment of nutritional differences corresponding to the various A. japonicus processing methods was conducted. The findings of this study can assist in the choice of sea cucumber products and the selection of suitable processing methods.

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