RESUMEN
As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality and lacks effective medical treatment. Increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established the mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potential mechanisms that mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which a lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI-positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating neurological functions. Besides, the IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in the acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.
Asunto(s)
Accidente Cerebrovascular Hemorrágico , Interleucina-13 , Fracturas de la Tibia , Animales , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Modelos Animales de Enfermedad , Accidente Cerebrovascular Hemorrágico/patología , Humanos , Interleucina-13/farmacología , Ratones , Piroptosis/efectos de los fármacos , Fracturas de la Tibia/complicaciones , Fracturas de la Tibia/metabolismo , Fracturas de la Tibia/patologíaRESUMEN
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Various forms of cells death are involved in the pathological process of TBI, without exception to ferroptosis, which is mainly triggered by iron-dependent lipid peroxidation. Although there have been studies on ferroptosis and TBI, the effect of ruxolitinib (Ruxo), one type of FDA approved drugs for treating myelofibrosis, on the process of ferroptosis post-TBI is remained non-elucidated. Therefore, using a controlled cortical impact device to establish the mouse TBI model, we examined the effect of Ruxo on TBI-induced ferroptosis, in which the inhibitor of ferroptosis, Ferrostatin-1 (Fer-1) was used as a positive control. Moreover, we also respectively explored the effects of these two interventions on neurological deficits caused by TBI. We firstly examined the expression patterns of ferroptosis-related markers at protein level at different time points after TBI. And based on the expression changes of these markers, we chose 12 h post-TBI to prove the effect of Ruxo on ferroptosis. Importantly, we found the intensely inhibitory effect of Ruxo on ferroptosis, which is in parallel with the results obtained after Fer-1-treatment. In addition, these two treatments both alleviated the content of brain water and degree of neurodegeneration in the acute phase of TBI. Finally, we further confirmed the neuroprotective effect of Ruxo or Fer-1 via the wire-grip test, Morris water maze and open field test, respectively. Thereafter, the lesion volume and iron deposition were also measured to certificate their effects on the long-term outcomes of TBI. Our results ultimately demonstrate that inhibiting ferroptosis exerts neuroprotection, and this is another neuroprotective mechanism of Ruxo on TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Modelos Animales de Enfermedad , Ferroptosis/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Pirazoles/uso terapéutico , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Ferroptosis/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Nitrilos , Pirazoles/farmacología , PirimidinasRESUMEN
BACKGROUND: To explore the clinical characteristics of neurocutaneous melanosis (NCM) in adult patients to help improve diagnosis and treatment of this disease, we present a rare case of an adult patient suffering from NCM with malignant melanoma, as well as a review of the relevant Chinese and English literature. CASE DESCRIPTION: The patient reported here plus the patients identified in our literature review total 30 adults with NCM (20 males [66.7%] and 10 females [33.3%]), age 19-65 years (average, 27.9 years). These include 24 cases of malignant melanoma (80.0%), 3 cases of melanocytoma (10.0%), 2 cases of diffuse melanocytosis (6.7%), and 1 case of unknown pathology (3.3%). Satellite nevi were reported in 25 cases (83.3%) and in 5 cases their presence was unknown (16.7%). Intracranial lesions were present in 28 cases (93.3%), and intraspinal lesions were present in 2 cases (6.7%). There are 4 cases of combined hydrocephalus (13.3%), and 2 cases of combined Dandy-Walker deformity (6.7%). CONCLUSIONS: NCM is a rare disease, especially in adults. With the onset of symptoms, the diagnosis is generally confirmed. In children with congenital giant nevus, regular periodic surveys of the central nervous system (brain and spinal cord) with magnetic resonance imaging or cerebrospinal fluid analysis should be performed to diagnose NCM. Active treatment should be undertaken to improve the prognosis.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Melanoma/diagnóstico por imagen , Melanoma/cirugía , Melanosis/diagnóstico por imagen , Melanosis/cirugía , Síndromes Neurocutáneos/diagnóstico por imagen , Síndromes Neurocutáneos/cirugía , Adulto , Neoplasias Encefálicas/complicaciones , Femenino , Humanos , Melanoma/complicaciones , Melanosis/complicaciones , Síndromes Neurocutáneos/complicacionesRESUMEN
OBJECTIVE: To explore the mechanism of miR-622 in regulating the proliferation, migration and invasion of cholangiocarcinoma (CCA) cells. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to measure the expression of miR-622 and c-Myc in CCA tissues and cell lines. Protein level of c-Myc was measured by Western blot. The effect of miR-622 on cell proliferation, migration and invasion was analyzed by MTT assay and Transwell chamber migration assay. Luciferase reporter assay was performed to measure the effect of miR-622 on c-Myc. RESULTS: miR-622 expression was downregulated in both CCA tissues and cell lines, while c-Myc expression was uregulated. Overexpression of miR-622 in CCA cells was statistically correlated with a decrease of cell proliferation, migration and invasion, while inhibition of miR-622 made an inverse result. We also proved c-Myc was identified as a target gene of miR-622 in CCA. Moreover, we found overexpression of c-Myc can strengthen the effects of miR-622 on the proliferation, migration and invasion of CCA cells. CONCLUSION: Decrease of miR-622 promotes the proliferation, migration and invasion of CCA cells by directly targeting c-Myc.