Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Jan 2018
Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux.
Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. ⋯ LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux.
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Biochem. Biophys. Res. Commun. · Jan 2018
DANFIN functions as an inhibitor of transcription factor NF-κB and potentiates the antitumor effect of bortezomib in multiple myeloma.
Nuclear factor-κB (NF-κB) proteins are transcription factors that play key roles in regulating most immune responses and cell death. Constitutively active NF-κB has been shown to exhibit chemoresistance by inducing anti-apoptosis in tumor cells. Multiple myeloma is known as a constitutive NF-κB activating disease, and the proteasome inhibitor bortezomib is used to treat multiple myeloma and mantle cell lymphoma. ⋯ In addition, DANFIN affected the IκBα binding region in Rel Homology Domain (RHD) and suppressed the nuclear translocalization of the p65 protein in cells. Furthermore, in multiple myeloma cells, DANFIN suppressed the expression level of NF-κB target genes and induced apoptosis. The combination therapy of DANFIN with bortezomib dramatically enhanced the apoptosis of multiple myeloma cells and indicated a remarkable anti-tumor effect in a multiple-myeloma xenograft mouse model.
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Endometriosis is a chronic, estrogen-dependent disease and characterized by the implantation of endometrial glands and stroma deep and haphazardly into the outside the uterine cavity. It affects an estimated 10% of the female population of reproductive age and results in obvious reduction in health-related quality of life. Unfortunately, there is no a consistent theory for the etiology of endometriosis. ⋯ However, autophagy is a friend or foe in endometriosis is puzzling, the precise mechanism underlying autophagy in endometriosis has not been fully elucidated yet. Here, we provide an integrated view on the acquired findings of the connections between endometriosis and autophagy. We also discuss which may contribute to the abnormal level of autophagy in endometriosis.
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Biochem. Biophys. Res. Commun. · Dec 2017
MicroRNA-126-3p attenuates blood-brain barrier disruption, cerebral edema and neuronal injury following intracerebral hemorrhage by regulating PIK3R2 and Akt.
MiR-126, a microRNA implicated in blood vessel integrity, angiogenesis and vascular inflammation, is markedly decreased in the sera of patients with intracerebral hemorrhage (ICH). The current study aims to evaluate the potential therapeutic effect of miR-126-3p on brain injuries in a rat model of collagenase-induced ICH. Intracerebroventricular administration of a miR-126-3p mimic significantly alleviated behavioral defects 24 h after ICH, as examined by paw placement and corner tests. ⋯ In addition, miR-126-3p mimic suppressed the upregulation of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) in the perihematomal area and maintained the activation of Akt. Furthermore, in vitro assays confirmed upregulation of PIK3R2 upon knockdown of miR-126-3p in rat brain microvascular endothelial cells (BMECs), and silencing of miR-126-3p resulted in impaired BMEC barrier permeability and reversed vascular endothelial growth factor (VEGF)- and angiopoietin-1 (Ang-1)-induced activation of Akt and inhibition of BMEC apoptosis. In summary, our results suggest that exogenous miR-126-3p may alleviate BBB disruption, cerebral edema and neuronal injury following ICH by targeting PIK3R2 and the Akt signaling pathway in brain vascular endothelium.
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Biochem. Biophys. Res. Commun. · Dec 2017
Fractalkine/CX3CR1 axis modulated the development of pancreatic ductal adenocarcinoma via JAK/STAT signaling pathway.
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an estimated 5 year survival rate of approximately 5% of all stages combined. High potential of PDAC metastasis is a leading cause for high mortality and poor prognosis. The majority of patients present with distant metastasis at diagnosis. ⋯ The underlying mechanism is that FKN/CX3CR1 activated JAK/STAT signaling, which in turn regulated cell growth. Consistently, in vivo tumorigenesis assay validated the regulatory role of FKN/CX3CR1 in PDAC growth. Our investigation helped understanding the pathogenesis of PDAC occurrence, and demonstrated critical role of FKN/CX3CR1 in PDAC development.