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It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.
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Infecciones por Coronavirus , Coronavirus , Dipeptidil Peptidasa 4 , Pangolines , Animales , Humanos , Ratones , Quirópteros , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Endopeptidasas/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Péptido Hidrolasas/metabolismo , Receptores Virales/metabolismo , Internalización del Virus , Coronavirus/fisiologíaRESUMEN
Schistosomiasis is a zoonotic parasitic disease. Schistosoma japonicum eggs deposited in the liver tissue induce egg granuloma formation and liver fibrosis, seriously threatening human health. Natural killer (NK) cells kill activated hepatic stellate cells (HSCs) or induce HSC apoptosis and inhibit the progression of liver fibrosis. However, the function of NK cells in liver fibrosis caused by S. japonicum infection is significantly inhibited. The mechanism of this inhibition remains unclear. Twenty mice were percutaneously infected with S. japonicum cercariae. Before infection and 2, 4, 6, and 8 weeks after infection, five mice were euthanized and dissected at each time point. Hepatic NK cells were isolated and transcriptome sequenced. The sequencing results showed that Tigit expression was high at 4-6 weeks post infection. This phenomenon was verified by reverse transcription quantitative PCR (RT-qPCR) and flow cytometry. NK cells derived from Tigit-/- and wild-type (WT) mice were co-cultured with HSCs. It was found that Tigit-/- NK cells induced apoptosis in a higher proportion of HSCs than WT NK cells. Schistosomiasis infection models of Tigit-/- and WT mice were established. The proportion and killing activity of hepatic NK cells were significantly higher in Tigit-/- mice than in WT mice. The degree of liver fibrosis in Tigit-/- mice was significantly lower than that in WT mice. NK cells were isolated from Tigit-/- and WT mice and injected via the tail vein into WT mice infected with S. japonicum. The degree of liver fibrosis in mice that received NK cell infusion reduced significantly, but there was no significant difference between mice that received NK cells from Tigit-/- and WT mice, respectively. Our findings indicate that Tigit knockout enhanced the function of NK cells and reduced the degree of liver fibrosis in schistosomiasis, thus providing a novel strategy for treating hepatic fibrosis induced by schistosomiasis.
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Receptores Inmunológicos , Schistosoma japonicum , Esquistosomiasis Japónica , Esquistosomiasis , Animales , Ratones , Células Asesinas Naturales/metabolismo , Hígado/patología , Cirrosis Hepática/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Esquistosomiasis/patologíaRESUMEN
In this study, fibrinolytic protease was isolated and purified from Perinereis aibuhitensis Grub, and the extraction process was optimized. The properties of the enzyme, such as the amino acid composition, thermal stability, optimal temperature, and pH, were investigated. After detoxification, proteins collected from fresh Clamworm (Perinereis aibuhitensis Grub) were concentrated via ammonium sulfate precipitation. The crude protease was purified using gel filtration resin (Sephadex G-100), anion exchange resin (DEAE-Sepharose FF), and hydrophobic resin (Phenyl Sepharose 6FF). The molecular weight of the protease was determined by polyacrylamide gel electrophoresis (SDS-PAGE). The optimum temperature and optimum pH of the protease were determined. The activity of crude protease in the 40-60% salt-out section was the highest, reaching 467.53 U/mg. The optimal process for purifying crude protein involved the application of DEAE-Sepharose FF and Phenyl Sepharose 6FF, which resulted in the isolation of a single protease known as Asp60-D1-P1 with the highest fibrinolytic activity; additionally, the enzyme activity was measured at 3367.76 U/mg. Analysis by Native-PAGE and SDS-PAGE revealed that the molecular weight of Asp60-D1-P1 was 44.5 kDa, which consisted of two subunits with molecular weights of 6.5 and 37.8 kDa, respectively. The optimum temperature for Asp60-D1-P1 was 40°C, and the optimal pH was 8.0.
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Fibrinolisina , Animales , Concentración de Iones de Hidrógeno , Fibrinolisina/metabolismo , Fibrinolisina/aislamiento & purificación , Poliquetos/enzimología , Temperatura , Peso Molecular , Estabilidad de Enzimas , Metales/farmacología , Electroforesis en Gel de Poliacrilamida , Fibrinolíticos/aislamiento & purificación , Fibrinolíticos/química , Fibrinolíticos/farmacología , Fibrinolíticos/metabolismoRESUMEN
Hyperlipidemia characterized by high blood levels of free fatty acids (FFAs) is important for the progression of inflammatory cardiovascular diseases. Integrin ß1 is a transmembrane receptor that drives various cellular functions, including differentiation, migration, and phagocytosis. However, the underlying mechanisms modifying integrin ß1 protein and activity in mediating monocyte/macrophage adhesion to endothelium remain poorly understood. In this study, we demonstrated that integrin ß1 protein underwent S-nitrosylation in response to nitrosative stress in macrophages. To examine the effect of elevated levels of FFA on the modulation of integrin ß1 expression, we treated the macrophages with a combination of oleic acid and palmitic acid (2:1) and found that FFA activated inducible nitric oxide synthase/nitric oxide and increased the integrin ß1 protein level without altering the mRNA level. FFA promoted integrin ß1 S-nitrosylation via inducible nitric oxide synthase/nitric oxide and prevented its degradation by decreasing binding to E3 ubiquitin ligase c-Cbl. Furthermore, we found that increased integrin α4ß1 heterodimerization resulted in monocyte/macrophage adhesion to endothelium. In conclusion, these results provided novel evidence that FFA-stimulated N--O stabilizes integrin ß1via S-nitrosylation, favoring integrin α4ß1 ligation to promote vascular inflammation.
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Células Endoteliales , Ácidos Grasos no Esterificados , Monocitos , Ácidos Grasos no Esterificados/metabolismo , Integrina alfa4beta1/metabolismo , Monocitos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Integrina beta1/metabolismo , Estabilidad Proteica , Células Endoteliales/metabolismo , Unión Proteica , Estrés FisiológicoRESUMEN
OBJECTIVES: To explore the value of whole tumour- and subregion-based radiomics of contrast-enhanced mammography (CEM) in differentiating the HER2 expression status of breast cancers. METHODS: 352 patients underwent preoperative CEM from two centres were consecutively enroled and divided into the training, internal validation, and external validation cohorts. The lesions were divided into HER2-positive and HER2-negative groups. Besides the radiological features, radiomics features capturing the whole tumour-based (wITH) and subregion-based intratumoral heterogeneity (sITH) were extracted from the craniocaudal view of CEM recombined images. The XGBoost classifier was applied to develop the radiological, sITH, and wITH models. A combined model was constructed by fusing the prediction results of the three models. RESULTS: The mean age of the patients was 51.1 ± 10.7 years. Two radiological features, four wITH features, and three sITH features were selected to establish the models. The combined model significantly improved the AUC to 0.80 ± 0.03 (95% CI: 0.73-0.86), 0.79 ± 0.06 (95% CI: 0.67-0.90), and 0.79 ± 0.05 (95% CI: 0.69-0.89) in the training, internal validation, and external validation cohorts, respectively (All P < 0.05). The combined model showed good agreement between the predicted and observed probabilities and favourable net clinical benefit in the validation cohorts. CONCLUSIONS: Both whole tumour- and subregion-based ITH radiomics features of CEM exhibited potential for differentiating the HER2 expression status. Combining conventional radiological features and ITH features can improve the model's performance.
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Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022. The primary end point was the proportion of patients with parathyroid hormone (PTH) levels less than or equal to 585 pg/mL at the end of follow-up. Secondary end points were the proportion of patients with normal calcium and phosphorus levels, the technical success rate, procedure-related complications, and improvement in self-rated hyperparathyroidism-related symptoms (0-3 ranking scale). The Wilcoxon signed rank test and generalized estimating equation model were used to evaluate treatment outcomes. Univariable and multivariable regression analyses identified variables associated with treatment failure (recurrent or persistent hyperparathyroidism). Results This study included 165 patients (median age, 51 years [IQR, 44-60 years]; 92 female) and 582 glands. RFA effectively reduced PTH, calcium, and phosphorus levels, with targeted ranges achieved in 78.2% (129 of 165), 72.7% (120 of 165), and 60.0% (99 of 165) of patients, respectively, at the end of follow-up (mean, 51 months). For the RFA sessions, the technical success rate was 100% (214 of 214). Median symptom scores (ostealgia, arthralgia, pruritus) decreased (all P < .001). Regarding complications, only hypocalcemia (45.8%, 98 of 214) was common. Treatment failure occurred in 36 patients (recurrent [n = 5] or persistent [n = 31] hyperparathyroidism). The only potential independent predictor of treatment failure was having less than four treated glands (odds ratio, 17.18; 95% CI: 4.34, 67.95; P < .001). Conclusion US-guided percutaneous RFA was effective and safe in the long term as a nonsurgical alternative for patients with SHPT undergoing dialysis; the only potential independent predictor of treatment failure was a lower number (<4) of treated glands. © RSNA, 2024 Supplemental material is available for this article.
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Calcio , Hiperparatiroidismo Secundario , Humanos , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Hiperparatiroidismo Secundario/diagnóstico por imagen , Hiperparatiroidismo Secundario/cirugía , FósforoRESUMEN
MOTIVATION: Cell membrane segmentation in electron microscopy (EM) images is a crucial step in EM image processing. However, while popular approaches have achieved performance comparable to that of humans on low-resolution EM datasets, they have shown limited success when applied to high-resolution EM datasets. The human visual system, on the other hand, displays consistently excellent performance on both low and high resolutions. To better understand this limitation, we conducted eye movement and perceptual consistency experiments. Our data showed that human observers are more sensitive to the structure of the membrane while tolerating misalignment, contrary to commonly used evaluation criteria. Additionally, our results indicated that the human visual system processes images in both global-local and coarse-to-fine manners. RESULTS: Based on these observations, we propose a computational framework for membrane segmentation that incorporates these characteristics of human perception. This framework includes a novel evaluation metric, the perceptual Hausdorff distance (PHD), and an end-to-end network called the PHD-guided segmentation network (PS-Net) that is trained using adaptively tuned PHD loss functions and a multiscale architecture. Our subjective experiments showed that the PHD metric is more consistent with human perception than other criteria, and our proposed PS-Net outperformed state-of-the-art methods on both low- and high-resolution EM image datasets as well as other natural image datasets. AVAILABILITY AND IMPLEMENTATION: The code and dataset can be found at https://github.com/EmmaSRH/PS-Net.
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Procesamiento de Imagen Asistido por Computador , Percepción , Humanos , Membrana Celular , Microscopía ElectrónicaRESUMEN
Hyperspectral imaging is a critical tool for gathering spatial-spectral information in various scientific research fields. As a result of improvements in spectral reconstruction algorithms, significant progress has been made in reconstructing hyperspectral images from commonly acquired RGB images. However, due to the limited input, reconstructing spectral information from RGB images is ill-posed. Furthermore, conventional camera color filter arrays (CFA) are designed for human perception and are not optimal for spectral reconstruction. To increase the diversity of wavelength encoding, we propose to place broadband encoding filters in front of the RGB camera. In this condition, the spectral sensitivity of the imaging system is determined by the filters and the camera itself. To achieve an optimal encoding scheme, we use an end-to-end optimization framework to automatically design the filters' transmittance functions and optimize the weights of the spectral reconstruction network. Simulation experiments show that our proposed spectral reconstruction network has excellent spectral mapping capabilities. Additionally, our novel joint wavelength encoding imaging framework is superior to traditional RGB imaging systems. We develop the deeply learned filter and conduct actual shooting experiments. The spectral reconstruction results have an attractive spatial resolution and spectral accuracy.
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Amino acid homeostasis is interconnected with the immune network of plants. During plant-pathogen interaction, amino acid transporters (AATs) have been shown to be involved in plant immune responses. However, the molecular mechanism by which how AATs function in this process remains elusive. In this study, we identify OsMP1 that acts as a quantitative trait locus against blast fungus from a joint analysis of GWAS and QTL mapping in rice. Heterogeneous expression of OsMP1 in yeast supports its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 is dramatically induced by Magnaporthe oryzae in the resistant landrace Heikezijing, while remaining unresponsive in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhances disease resistance to blast fungus and leaf-blight bacterium without yield penalty. Furthermore, the overexpression of OsMP1 leads to increased accumulation of Thr, Ser, Phe and His in the leaves. And the heightened levels of these amino acids contribute to reduced disease susceptibility, which is associated with upregulated jasmonic acid pathway. Thus, our results elucidate the pivotal role of OsMP1 in disease resistance and provide a potential target for breeding more resistant rice cultivars without compromising yield.
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Snapshot multispectral imaging (SMSI) has attracted much attention in recent years for its compact structure and superior performance. High-level image analysis based on SMSI, such as object classification and recognition, usually takes the image reconstruction as the first step, which hinders its application in many important real-time scenarios. Here we demonstrate the first, to our knowledge, reconstruction-free strategy for object detection with SMSI in the short-wave infrared (SWIR) band. The implementation of our SMSI is based on a modified 4f system which modulates the light with a random phase mask, and the distinctive point spread function in each narrowband endows the system with spectrum resolving ability. A deep learning network with a CenterNet structure is trained to detect a small object by constructing a dataset with the PSF of our SMSI system and the sky images as background. Our results indicate that a small object with a spectral feature can be detected directly with the compressed image output by our SMSI system. This work paves the way toward the use of SMSI to detect a multispectral object in practical applications.
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Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic beads and cultured. Western blot was used to assess NLRP3 inflammasomes. Interleukin-1ß (IL-1ß) and IL-18 were measured using enzyme-linked immunosorbent assay. Here we showed that the NLRP3 inflammasome was activated in non-obese diabetic (NOD) mice with SS-like manifestations. We found that NLRP3 inflammasome activation was augmented in MDSCs of SS mice and NLRP3 inflammasome activation was suppressed in IL-27-deficient NOD mice. Consistent with findings of SS mice in vivo, we observed that NLRP3 inflammasome activation by adenosine triphosphate and lipopolysaccharide was remarkably intensified in MDSCs with IL-27 treatment in vitro. Collectively, our data highlighted that IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental SS.
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Interleucina-27 , Células Supresoras de Origen Mieloide , Síndrome de Sjögren , Animales , Ratones , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
BACKGROUND: Psoriasis is a common chronic skin disorder. Pathologically, it features abnormal epidermal proliferation, infiltrating inflammatory cells and increased angiogenesis in the dermis. Aberrant expression of E3 ubiquitin ligase and a dysregulated protein ubiquitination system are implicated in the pathogenesis of psoriasis. OBJECTIVES: To examine the potential role of S-phase kinase-associated protein 2 (Skp2), an E3 ligase and oncogene, in psoriasis. METHODS: Gene expression and protein levels were evaluated with quantitative reverse transcriptase polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence staining of skin samples from patients with psoriasis vulgaris and an imiquimod (IMQ)-induced mouse model, as well as from cultured endothelial cells (ECs). Protein interaction, substrate ubiquitination and degradation were examined using co-immunoprecipitation, Western blotting and a cycloheximide chase assay in human umbilical vein ECs. Angiogenesis was measured in vitro using human dermal microvascular ECs (HDMECs) for BrdU incorporation, migration and tube formation. In vivo angiogenesis assays included chick embryonic chorioallantoic membrane, the Matrigel plug assay and quantification of vasculature in the mouse lesions. Skp2 gene global knockout (KO) mice and endothelial-specific conditional KO mice were used. RESULTS: Skp2 was increased in skin samples from patients with psoriasis and IMQ-induced mouse lesions. Immunofluorescent double staining indicated a close association of Skp2 expression with excessive vascularity in the lesional dermal papillae. In HDMECs, Skp2 overexpression was enhanced, whereas Skp2 knockdown inhibited EC proliferation, migration and tube-like structure formation. Mechanistically, phosphatase and tensin homologue (PTEN), which suppresses the phosphoinositide 3-kinase/Akt pathway, was identified to be a novel substrate for Skp2-mediated ubiquitination. A selective inhibitor of Skp2 (C1) or Skp2 small interfering RNA significantly reduced vascular endothelial growth factor-triggered PTEN ubiquitination and degradation. In addition, Skp2-mediated ubiquitination depended on the phosphorylation of PTEN by glycogen synthase kinase 3ß. In the mouse model, Skp2 gene deficiency alleviated IMQ-induced psoriasis. Importantly, tamoxifen-induced endothelial-specific Skp2 KO mice developed significantly ameliorated psoriasis with diminished angiogenesis of papillae. Furthermore, topical use of the Skp2 inhibitor C1 effectively prevented the experimental psoriasis. CONCLUSIONS: The Skp2/PTEN axis may play an important role in psoriasis-associated angiogenesis. Thus, targeting Skp2-driven angiogenesis may be a potential approach to treating psoriasis.
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Psoriasis , Proteínas Quinasas Asociadas a Fase-S , Humanos , Animales , Ratones , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Tensinas/metabolismo , Células Endoteliales/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Angiogénesis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Psoriasis/patología , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
The development of the goat mammary gland is mainly under the control of ovarian hormones particularly estrogen and progesterone (P4). Amino acids play an essential role in mammary gland development and milk production, and sodium-coupled neutral amino acid transporter 2 (SNAT2) was reported to be expressed in the mammary gland of rats and bovine mammary epithelial cells, which may affect the synthesis of milk proteins or mammary cell proliferation by mediating prolactin, 17ß-estradiol (E2) or methionine function. However, whether SNAT2 mediates the regulatory effects of E2 and P4 on the development of the ruminant mammary gland is still unclear. In this study, we show that E2 and P4 could increase the proliferation of goat mammary epithelial cells (GMECs) and regulate SNAT2 mRNA and protein expression in a dose-dependent manner. Further investigation revealed that SNAT2 is abundantly expressed in the mammary gland during late pregnancy and early lactation, while knockdown and overexpression of SNAT2 in GMECs could inhibit or enhance E2- and P4-induced cell proliferation as well as mammalian target of rapamycin (mTOR) signaling. We also found that the accelerated proliferation induced by SNAT2 overexpression in GMECs was suppressed by the mTOR signaling pathway inhibitor rapamycin. This indicates that the regulation of GMECs proliferation mediated by SNAT2 in response to E2 and P4 is dependent on the mTOR signaling pathway. Finally, we found that the total content of the amino acids in GMECs changed after knocking-down and overexpressing SNAT2. In summary, the results demonstrate that the regulatory effects of E2 and P4 on GMECs proliferation may be mediated by the SNAT2-transported amino acid pathway. These results may offer a novel nutritional target for improving the development of the ruminant mammary gland and milk production.
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Estrógenos , Cabras , Progesterona , Animales , Femenino , Embarazo , Aminoácidos/metabolismo , Proliferación Celular , Células Epiteliales/metabolismo , Estrógenos/metabolismo , Cabras/genética , Cabras/metabolismo , Glándulas Mamarias Animales/metabolismo , Progesterona/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.
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Lectinas Tipo C , Neoplasias , Receptores Inmunológicos , Humanos , Receptores Inmunológicos/metabolismo , Lectinas Tipo C/metabolismo , Lectinas Tipo C/antagonistas & inhibidores , Animales , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Biomarcadores/metabolismo , Transducción de Señal , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , InmunoterapiaRESUMEN
Ferroptosis is a newly recognized type of regulated cell death that is characterized by the accumulation of iron and lipid peroxides in cells. Studies have shown that ferroptosis plays a significant role in the pathogenesis of various diseases, including cardiovascular diseases. In cardiovascular disease, ferroptosis is associated with ischemia-reperfusion injury, myocardial infarction, heart failure, and atherosclerosis. The molecular mechanisms underlying ferroptosis include the iron-dependent accumulation of lipid peroxidation products, glutathione depletion, and dysregulation of lipid metabolism, among others. This review aims to summarize the current knowledge of the molecular mechanisms of ferroptosis in cardiovascular disease and discuss the potential therapeutic strategies targeting ferroptosis as a treatment for cardiovascular disease.
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Enfermedades Cardiovasculares , Ferroptosis , Humanos , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Animales , Peroxidación de Lípido , Hierro/metabolismo , Metabolismo de los LípidosRESUMEN
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
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PURPOSE: The goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture that surround the tumor area. The brain adjacent tumor area (BAT) is defined as the region adjacent to the gross tumor volume, which contains signal abnormalities on T2-weighted or FLAIR sequences. The DTI-FT analysis of the BAT can be adopted as predictive values and a guide for safe tumor resection. METHODS: This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric "tract irregularity" (TI) grade, comparing it with the surgical series' clinical, radiological, and outcome data. RESULTS: The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p = 0.001). The relationship appears directly proportional regarding MD values (p = 0.003) and TI values (p = 0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p = 0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p = 0,05), PFS (p < 0.001), and EOR (p < 0.01). CONCLUSION: FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning.
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Utilizing the strong ligand control effects of l-cysteine (l-Cys), the growth of Au on Au triangular nanoplate (AuTN) seeds was continuously tuned from layer-by-layer (the Frank-van der Merwe) to layer-plus-island (the Stranski-Krastanov), and island (the Volmer-Weber) growth modes, leading to the formation of a series of Au-on-AuTN heterostructures. Within the window of VW growth mode (featured by the growth of Au spikes and branches on AuTNs), the effective localized surface plasmon resonance (LSPR) coupling led to the selective strengthening of the "valley" absorptions, leading to smooth and flat absorption curves. Interestingly, through engineering the number/density, size, and branching degree of the Au branches, except for the black color, full spectrum absorption within 400-1300 nm wavelength was achieved on Au-branch-on-AuTN structures. Mechanistic studies revealed that the blackbody absorption property of the Au-branch-on-AuTN originates from the well-balanced intraparticle LSPR couplings among the neighboring Au branches. The tunable blackness and the full spectrum absorption property made the Au-branch-on-AuTN heterostructure a suitable candidate for various plasmonic-related applications, such as a wide spectrum light absorber, photoacoustic imaging contrast agent, and photothermal therapy medium. In addition, our strong ligand control in Au-branch-on-AuTN heterostructures could be extended to other hybrid systems with diverse material combinations, so long as to find the proper strong ligand.
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Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it's hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Estimulación Magnética Transcraneal , Accidente Cerebrovascular/complicaciones , Factores de TiempoRESUMEN
Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.