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Mechanical damage to a cell can be fatal, and the cell must reseal its membrane and restore homeostasis to survive. Plant cell repair involves additional steps such as rebuilding vacuoles, rearranging chloroplasts, and remodeling the cell wall. When we pierced a Griffithsia monilis cell with a glass needle, a large amount of intracellular contents was released, but the cell membrane resealed in less than a second. The turgor of the vacuole was quickly restored, and the punctured cell returned to its original shape within an hour. Organelles such as chloroplasts and nuclei migrated to the wound site for 12 h and then dispersed throughout the cell after the wound was covered by a new cell wall. Using fluorescent probes, high levels of reactive oxygen species (ROS) and calcium were detected at the wound site from 3 h after wounding, which disappeared when cell repair was complete. Wounding in a solution containing ROS scavengers inhibited cellular repair, and inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity or blocking calcium influx reversibly inhibited cell repair. Oryzalin reversibly inhibited both chloroplast movement and ROS production during cell repair. Our results show that cell repair in G. monilis is regulated by calcium-mediated ROS signaling and that microtubules serve as mechanical effectors.
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Understanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to tissue damage and degenerative osteoarthritis. Recently, we have discovered that mechanical injury to connective tissues including murine and porcine articular cartilage causes a significant increase in lysine-63 polyubiquitination. Here, we identified the ubiquitin signature that is unique to injured articular cartilage tissue upon mechanical injury (the "mechano-ubiquitinome"). A total of 463 ubiquitinated peptides were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum (ER), also known as the ER-associated degradation response, including YOD1, BRCC3, ATXN3, and USP5 as well as the ER stress regulators, RAD23B, VCP/p97, and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB-specific activity probes. Combined, these results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and in osteoarthritic cartilage tissues. This link through the ER-associated degradation pathway makes this protein set attractive for further investigation in in vivo models of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases.
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Cartílago Articular , Enfermedades Musculoesqueléticas , Osteoartritis , Humanos , Animales , Ratones , Porcinos , Cartílago Articular/metabolismo , Pez Cebra/metabolismo , Ubiquitinación , Estrés del Retículo Endoplásmico , Retículo Endoplásmico/metabolismo , Ubiquitina/metabolismo , Péptidos/metabolismo , Enfermedades Musculoesqueléticas/metabolismo , Osteoartritis/metabolismoRESUMEN
BACKGROUND: Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex. METHODS: Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24-36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150-200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks. RESULTS: A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045). CONCLUSIONS: Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.
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Folículo Ovárico , Ovario , Animales , Femenino , Humanos , Ratones , Proteína X Asociada a bcl-2 , Criopreservación/métodos , Neovascularización Fisiológica , Trasplante Heterólogo , AdultoRESUMEN
Spinal cord injury (SCI), resulting in damage of the normal structure and function of the spinal cord, would do great harm to patients, physically and psychologically. The mechanism of SCI is very complex. At present, lots of studies have reported that autophagy was involved in the secondary injury process of SCI, and several researchers also found that calcium ions (Ca2+) played an important role in SCI by regulating necrosis, autophagy, or apoptosis. However, to our best of knowledge, no studies have linked the spinal cord mechanical injury, intracellular Ca2+, and autophagy in series. In this study, we have established an in vitro model of SCI using neural cells from fetal rats to explore the relationship among them, and found that mechanical injury could promote the intracellular Ca2+ concentration, and the increased Ca2+ level activated autophagy through the CaMKKß/AMPK/mTOR pathway. Additionally, we found that apoptosis was also involved in this pathway. Thus, our study provides new insights into the specific mechanisms of SCI and may open up new avenues for the treatment of SCI.
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Proteínas Quinasas Activadas por AMP , Traumatismos de la Médula Espinal , Ratas , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Autofagia , Médula Espinal/metabolismo , ApoptosisRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the duration of fixation of adhesive films in the treatment of traumatic lesions of the oral mucosa. MATERIAL AND METHODS: The patients were divided into 2 groups. In the first group, the affected area was covered with an adhesive film with solcoseryl, in the second group with a film with vitamin E. The film was glued to the affected area according to the instructions, the time of gluing was recorded, patients were warned about the need to notify researchers via messengers or SMS messages about the time of peeling or resorption of the film. The evaluation was carried out by the method of variation statistics (Student's t-test for independent samples). RESULTS: The retention time of the film in the oral cavity was expressed in minutes, the average value in group 1 was 48.4±9.19, in group 2 - 127.70±49.07. Thus, the fixation of the film with vitamin E was longer than the films with solcoseryl (p=0.000180). CONCLUSION: Both films provided sufficient protective effect during the retention period. However, in clinical situations where a longer barrier protective effect to the damaged oral mucosa surface is required, it is advisable to use a vitamin E healing patch.
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Actiemil , Mucosa Bucal , Humanos , Actiemil/uso terapéutico , Cementos Dentales , Vitamina E/uso terapéuticoRESUMEN
We investigated hyphae regeneration in Trichoderma atroviride and Neurospora crassa, with particular focus on determining the role of the actin cytoskeleton after mechanical injury. Filamentous actin (F-actin) dynamics was observed by live-cell confocal microscopy in both T. atroviride and N. crassa strains expressing Lifeact-GFP. In growing hyphae of both fungi, F-actin localized in three different structural forms: patches, cables and actomyosin rings. Most patches were conspicuously arranged in a collar in the hyphal subapex. A strong F-actin signal, likely actin filaments, colocalized with the core of the Spitzenkörper. Filaments and cables of F-actin were observed along the cortex throughout hyphae. Following mechanical damage at the margin of growing mycelia of T. atroviride and N. crassa, the severed hyphae lost their cytoplasmic contents, but plugging of the septal pore by a Woronin body occured, and the rest of the hyphal tube remained whole. In both fungi, patches of F-actin began accumulating next to the plugged septum. Regeneration was attained by the emergence of a new hyphal tube as an extension of the plugged septum wall. The septum wall was gradually remodeled into the apical wall of the emerging hypha. Whereas in T. atroviride the re-initiation of polarized growth took â¼ 1 h, in N. crassa, actin patch accumulation began almost immediately, and new growing hyphae were observed â¼ 30 min after injury. By confocal microscopy, we found that chitin synthase 1 (CHS-1), a microvesicle (chitosome) component, accumulated next to the plugged septum in regenerating hyphae of N. crassa. We concluded that the actin cytoskeleton plays a key role in hyphal regeneration by supporting membrane remodeling, helping to facilitate transport of vesicles responsible for new wall growth and organization of the new tip-growth apparatus.
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Lepidópteros , Neurospora crassa , Citoesqueleto de Actina/genética , Actinas/genética , Animales , Hifa , Hypocreales , Neurospora crassa/genéticaRESUMEN
The study objective was to investigate soft tissue microcirculation in the area of a lower limb long bone fracture. We studied fractures of the lower limb long bones from 0 to 7 days of age in 17 males and 37 females. The mean age of patients was 57.33±2.53 years. Histological examination of soft tissues from the area of the lower limb long bone fracture and at the distance from the fracture was performed. Standard hematoxylin and eosin staining was used. The thickness and diameter of arterioles, venules, and capillaries were evaluated by morphometry of the sections made. The observed pattern reflects the response of the microcirculation of the soft tissues to the mechanical impact. The relative ratio of the artery diameter to the small-caliber vein diameter was 1.01±0.13, and the artery wall thickness to the vein wall thickness was 2.03±0.28, which can be considered a natural reaction of the microcirculation blood vessels to the mechanical impact in 1-1.5 weeks after the formed fracture of the lower limb long bone.
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Fracturas Óseas , Traumatismos de la Pierna , Arterias , Femenino , Fracturas Óseas/diagnóstico por imagen , Humanos , Extremidad Inferior , Masculino , Microcirculación/fisiología , Persona de Mediana EdadRESUMEN
OBJECTIVE: Analysis of the violent death structure in the Russian Federation; determination of the changes dynamics in indicators of its main types and identification of the most common ones. Currently, there are no studies with the results of a total data analysis on injuries in the Russian Federation. A number of scientific works devoted to the statistical analysis of injuries touch on short-term periods in individual subjects of the Russian Federation and certain types of injuries. The authors present the results of a detailed analysis of violent death's statistical indicators that can contribute to the monitoring of medical and statistical indicators for the implementation of priority and strategic directions in the health sector, improvement of legal regulation and other measures to strengthen public health and prevent risk factors. The dynamics of changes in various injuries types for the indicated period has been established. The most common types of violent death have been identified; the patterns of decrease and increase in certain death types have been established.
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Causas de Muerte , Humanos , Factores de Riesgo , Federación de RusiaRESUMEN
OBJECTIVE: Interleukin (IL)-1ß in the joint cavity increases to promote healing after anterior cruciate ligament (ACL) injury. Synovial tissue is a major joint microenvironmental regulator after ACL injury. The purpose of this study was to investigate the effects of synovial cells (SCs) on lysyl oxidase (LOX) and matrix metalloproteinase (MMP) production by ACL fibroblasts (ACLfs) in the presence of IL-1ß. RESULTS: This study sheds light on the regulation of LOX and MMP-1, -2, -3 expression by ACLfs co-cultured with SCs and treated with IL-1ß. LOX and MMP-1, 2, 3 gene/protein expression in IL-1ß/stretch-stimulated ACLfs co-cultured with SCs were measured by real-time quantitative PCR and Western blot. Meanwhile, MMP-2 activity was analyzed by zymogram. The results showed that co-culture with SCs increased LOX and MMP-1, -2, -3 gene and protein expression in the presence of IL-1ß. Next, ACLfs were subjected to 12% mechanical stretch to simulate pathological injury. Under these conditions, SCs inhibited IL-1ß-mediated upregulation of LOXs. However, IL-1ß enhanced the expression of MMP-1, -2, -3 in injured ACLfs. CONCLUSIONS: SCs can either inhibit or increase LOX production in the presence of IL-1ß, while promoting the accumulation of MMP in injured ACLfs. These results may provide crucial insights into the mechanisms underlying ACL poor healing capacity after injury.
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Fibroblastos , Interleucina-1beta/metabolismo , Metaloproteinasas de la Matriz Secretadas/metabolismo , Proteína-Lisina 6-Oxidasa/metabolismo , Sinoviocitos , Adulto , Ligamento Cruzado Anterior/citología , Lesiones del Ligamento Cruzado Anterior/metabolismo , Microambiente Celular , Técnicas de Cocultivo , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Sinoviocitos/citología , Sinoviocitos/metabolismoRESUMEN
OBJECTIVE: The purpose of this study is to investigate whether mechanical growth factor (MGF) promotes mechanical response to ligament fibroblasts in osteoarthritis knee cavity via activating transcription factor 2 (ATF-2). RESULTS: Osteoarthritis ligament fibroblasts (OA-LFs) were suffered from 12% static mechanical stretch to mimic mechanical force mediated ligament injury. Meanwhile, OA-LFs were treated with MGF before and during mechanical stretch. We observed that OA delayed LFs response to mechanical injury, while MGF pretreatment promoted cells timely feedback the mechanically stimuli by inducing cellular stress. Additionally, MGF accelerated the ligament injury repair by promoting cell migration, decreasing the MMP-2 activity, and remitting the cell deformation via ATF-2 activating in cells. CONCLUSIONS: Our study shows that MGF pretreatment of OA-LFs can respond quickly to mechanical damage and repair ligament tissue by activating ATF-2. Therefore, MGF has potential as a therapeutic for OA patients.
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Factor de Transcripción Activador 2/metabolismo , Ligamento Cruzado Anterior/citología , Fibroblastos/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/farmacología , Osteoartritis de la Rodilla/metabolismo , Adulto , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Fibroblastos/fisiología , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population.
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Enfermedades del Sistema Nervioso Central/patología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Receptores Purinérgicos P2X7/metabolismo , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/metabolismo , Dolor Crónico/metabolismo , Dolor Crónico/fisiopatología , Epilepsia/metabolismo , Epilepsia/fisiopatología , Humanos , Ratones Transgénicos , Neuralgia/metabolismo , Neuralgia/patología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2X/farmacología , Receptores Purinérgicos P2X7/deficienciaRESUMEN
Atherosclerosis (AS) is the main pathological basis for the occurrence of many vascular diseases and has a strong association with metabolic syndrome. Peripheral arterial diseases caused by AS have high morbidities and mortalities but lack still effective treatment. AS animal models are highly valuable for research on peripheral arteriosclerotic diseases. While small and medium AS animal models based on high-fat feeding and balloon injuries have been successfully established,few literatures have described the creation of large animal models for AS treatment. This article elucidates the current methods for creating medium and large animal models of peripheral atherosclerotic disease,with an attempt to further promote the clinical translation of AS treatment research.
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Aterosclerosis , Modelos Animales de Enfermedad , Animales , Humanos , Síndrome MetabólicoRESUMEN
We assessed the incidence of mechanical injury in drug users. Incidence was 21.9% and exceeds the global average injury rate by 2.4 times Mortality from mechanical injury among drug users ranges from 4.46% to 5%. This value is 4.46-5%, which is 64-71 times higher than the average mortality rates from injury and 89-100 times higher than trauma mortality rate in Russia. Psychoactive drugs from the groups of neurostimulators and neurodepressors have a significant impact on the course of traumatic brain injury; hallucinogens only increase the risk of traumatic injury. In cases of mild traumatic brain injury and concussion combined with drug intoxication, the action of the psychoactive drug is the leading link of pathogenesis. In cases of moderate to severe traumatic brain injury combined with drug intoxication, craniocerebral trauma determines the outcome.
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Conmoción Encefálica/epidemiología , Lesiones Traumáticas del Encéfalo/epidemiología , Traumatismos Craneocerebrales/epidemiología , Consumidores de Drogas , Humanos , Incidencia , Federación de Rusia/epidemiologíaRESUMEN
OBJECTIVE: We recently demonstrated that low-energy mechanical impact to articular cartilage, usually considered non-injurious, can in fact cause microscale cracks (widths <30µm) in the collagen network of visually pristine human cartilage. While research on macro-scale cracks in cartilage and microcracks in bone abounds, how microcracks within cartilage initiate and propagate remains unknown. We quantified the extent to which microcracks initiate and propagate in the collagen network during mechanical loading representative of normal activities. DESIGN: We tested 76 full-thickness, cylindrical osteochondral plugs. We imaged untreated specimens (pristine phase) via second harmonic generation and assigned specimens to three low-energy impact groups (none, low, high), and thereafter to three cyclic compression groups (none, low, high) which simulate walking. We re-imaged specimens in the post-impact and post-cyclic compression phases to identify and track microcracks. RESULTS: Microcracks in the network of collagen did not present in untreated controls but did initiate and propagate under mechanical treatments. We found that the length and width of microcracks increased from post-impact to post-cyclic compression in tracked microcracks, but neither depth nor angle presented statistically significant differences. CONCLUSIONS: The microcracks we initiated under low-energy impact loading increased in length and width during subsequent cyclic compression that simulated walking. The extent of this propagation depended on the combination of impact and cyclic compression. More broadly, the initiation and propagation of microcracks may characterize pathogenesis of osteoarthritis, and may suggest therapeutic targets for future studies.
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Cartílago Articular/patología , Colágeno/ultraestructura , Animales , Cartílago Articular/ultraestructura , Bovinos , Fuerza Compresiva , Humanos , Estrés Mecánico , Soporte de PesoRESUMEN
The objective of the present work was to analyze the results and efficiency of forensic medical expertises and investigations of the cases of the fatal mechanical injury in Russia carried out during the period from 2003 to 2017. The analysis included the data on the structure and personnel scheduling charts of the departments of forensic medical expertise of the corpses in the state-governed forensic medical expertise institutions. It was shown that the structure of the fatal mechanical injury differs in different regions of the country: some of them are characterized by the predominance of blunt traumas whereas road traffic injuries prevail in others. In addition, the analysis of the regional distribution of the gunshot injuries was carried out.
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Accidentes de Tránsito/mortalidad , Heridas por Arma de Fuego/mortalidad , Heridas no Penetrantes/mortalidad , Cadáver , Humanos , Federación de Rusia/epidemiologíaRESUMEN
PURPOSE: We establish a mechanical injury model for articular cartilage to assess the sensitivity of diffusion tensor imaging (DTI) in detecting cartilage damage early in time. Mechanical injury provides a more realistic model of cartilage degradation compared with commonly used enzymatic degradation. METHODS: Nine cartilage-on-bone samples were obtained from patients undergoing knee replacement. The 3 Tesla DTI (0.18 × 0.18 × 1 mm3 ) was performed before, 1 week, and 2 weeks after (zero, mild, and severe) injury, with a clinical radial spin-echo DTI (RAISED) sequence used in our hospital. We performed stress-relaxation tests and used a quasilinear-viscoelastic (QLV) model to characterize cartilage mechanical properties. Serial histology sections were dyed with Safranin-O and given an OARSI grade. We then correlated the changes in DTI parameters with the changes in QLV-parameters and OARSI grades. RESULTS: After severe injury the mean diffusivity increased after 1 and 2 weeks, whereas the fractional anisotropy decreased after 2 weeks (P < 0.05). The QLV-parameters and OARSI grades of the severe injury group differed from the baseline with statistical significance. The changes in mean diffusivity across all the samples correlated with the changes in the OARSI grade (r = 0.72) and QLV-parameters (r = -0.75). CONCLUSION: DTI is sensitive in tracking early changes after mechanical injury, and its changes correlate with changes in biomechanics and histology. Magn Reson Med 78:69-78, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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Cartílago Articular/diagnóstico por imagen , Cartílago Articular/lesiones , Imagen de Difusión Tensora/métodos , Fracturas del Cartílago/diagnóstico por imagen , Fracturas del Cartílago/fisiopatología , Interpretación de Imagen Asistida por Computador/métodos , Adulto , Cartílago Articular/fisiopatología , Módulo de Elasticidad , Femenino , Fracturas del Cartílago/patología , Humanos , Traumatismos de la Rodilla/diagnóstico por imagen , Traumatismos de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estrés Mecánico , ViscosidadRESUMEN
Alterations in the activity of neural circuits are a common consequence of traumatic brain injury (TBI), but the relationship between single-neuron properties and the aggregate network behavior is not well understood. We recently reported that the GluN2B-containing NMDA receptors (NMDARs) are key in mediating mechanical forces during TBI, and that TBI produces a complex change in the functional connectivity of neuronal networks. Here, we evaluated whether cell-to-cell heterogeneity in the connectivity and aggregate contribution of GluN2B receptors to [Ca(2+)]i before injury influenced the functional rewiring, spontaneous activity, and network plasticity following injury using primary rat cortical dissociated neurons. We found that the functional connectivity of a neuron to its neighbors, combined with the relative influx of calcium through distinct NMDAR subtypes, together contributed to the individual neuronal response to trauma. Specifically, individual neurons whose [Ca(2+)]i oscillations were largely due to GluN2B NMDAR activation lost many of their functional targets 1 h following injury. In comparison, neurons with large GluN2A contribution or neurons with high functional connectivity both independently protected against injury-induced loss in connectivity. Mechanistically, we found that traumatic injury resulted in increased uncorrelated network activity, an effect linked to reduction of the voltage-sensitive Mg(2+) block of GluN2B-containing NMDARs. This uncorrelated activation of GluN2B subtypes after injury significantly limited the potential for network remodeling in response to a plasticity stimulus. Together, our data suggest that two single-cell characteristics, the aggregate contribution of NMDAR subtypes and the number of functional connections, influence network structure following traumatic injury.
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Lesiones Encefálicas/metabolismo , Red Nerviosa/metabolismo , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Lesiones Encefálicas/fisiopatología , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Red Nerviosa/fisiopatología , Fenotipo , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genéticaRESUMEN
The present study established a novel and reproducible animal model to study abdominal aortic aneurysms. In total, 22 adult Lewis rats underwent a procedure to produce mechanical injuries at the infrarenal aorta which was opened temporarily. The aortas were injured 6 times and repaired. Those rats were divided into 2 groups and the aortic aneurysm tissue was harvested after 42 (6-week group) or 63 (9-week group) days and evaluated for the progression of aortic aneurysms. In the 6-week group, changes in the aneurysm were observed in 6/10 (60%) rats and the mean maximum diameter of the aorta demonstrated a 119% increase in size from the baseline measurement. In the 9-week group, changes in the aneurysm were observed in 8/11 (88%) rats and the mean maximum diameter of aorta demonstrated a 133% increase in size. Additional findings from the aortic aneurysm tissue were found microscopically, including the destruction of the tunica media and the elastic fiber. The present study demonstrated that this novel animal model for the development of abdominal aortic aneurysms (AAAs) produced by mechanical injury may have high reproducibility and similar gross and microscopic morphology to humans. This model could be helpful to investigate the treatment of AAAs.
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We aimed developing and experimentally validating methods for 3D scale-selective polarimetry of multiply scattered fields in diffuse myocardium layers for mechanical myocardial injury prescription histological differential diagnostics. We used the synthesis of diffuse object field polarization-interference registration and polarization-inhomogeneous field digital holographic reconstruction and layer-by-layer complex amplitudes distributions The method for selection single and diffuse object field multiply scattered components polarization maps is proposed. The conditions for eliminating the distorting influence of a depolarized background high level are found. On the basis of еÑÑ object field single scattered component polarization maps a large-scale selective wavelet analysis the criteria (markers) for mechanical myocardial injury different prescription diagnosis was determinate. Excellent accuracy mechanical injury myocardium necrotic changes with different duration using polarization-interference wavelet differentiation were achieved.
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Corazón , Miocardio , Miocardio/patología , Corazón/diagnóstico por imagenRESUMEN
Drosophila melanogaster crystal cells are a specialized type of blood cells for innate immune process upon injury. Under normal conditions, crystal cells rarely proliferate and constitute a small proportion of fly blood cells. Notch signaling has been known to guide the cell fate determination of crystal cells and maintain their survival. Here, we reported that protein phosphatase V (PpV), the unique catalytic subunit of protein phosphatase 6 in Drosophila, is a novel regulator of crystal cell proliferation and integrity. We found that PpV proteins highly accumulated in crystal cells in the larval hematopoietic organ termed the lymph gland. Silencing PpV using RNA interference led to increased crystal cell proliferation in a Notch-independent manner and induced crystal cell rupture dependent on Notch signaling. Moreover, additive PpV prevented the rupture of crystal cells in lymph glands upon a needle injury, suggesting the involvement of PpV in wound healing. Altogether, our results indicated that PpV plays a dual role in lymph glands, preventing crystal cell proliferation to limit the cell number, as well as inhibiting crystal cell rupture to maintain their survival.