Tissue plasminogen activator (tPA) is an essential component of the proteolytic cascade that lyses blood clots. Various studies also suggest that tPA plays important roles in the nervous system. We show that exogenous tPA or tPA/plasminogen (plg) promotes axonal regeneration, remyelination, and functional recovery after sciatic nerve injury in the mouse. Local application of tPA or tPA/plg 7 days after sciatic nerve crush significantly increased the total number of axons and myelinated axons, which is accompanied by enhanced expression of neurofilament. Treatment with tPA or tPA/plg reduced the deposition of fibrin(ogen) after nerve injury. Moreover, tPA or tPA/plg increased the number of macrophages and induced MMP-9 expression at the injury site, coincident with reduced collagen scar formation and accelerated clearance of myelin and lipid debris after treatment. Consequently, tPA or tPA/plg treatment protected muscles from atrophy after nerve injury, indicating better functional recovery. These results suggest that administration of exogenous tPA or tPA/plg promotes axonal regeneration and remyelination through removal of fibrin deposition and activation of MMP-9-positive macrophages, which may be responsible for myelin debris clearance and preventing collagen scar formation. Therefore, tPA may be useful for treatment of peripheral nerve injury.
These results suggested that MALDI-TOF MS combined with MB separation yields significantly higher sensitivity and specificity for the detection of serum protein in patients with ESCC.
IMPORTANCE Palliative radiotherapy (RT) is generally recommended for older patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis. A new combination treatment is therefore needed. OBJECTIVE To assess the efficacy and toxicity of RT plus icotinib vs RT alone in older patients with ESCC.
Deficiency of tPA aggravated liver fibrosis through promoting hepatic stellate cells (HSCs) activation and inhibiting ECM degradation by decreasing MMP-2, MMP-9 activities and disrupting the balance between MMP-13 and TIMP-1.
Apoptosis or necrosis of neurons in the central nervous system (CNS) is the hallmark of many neurodegenerative diseases and Traumatic Brain Injury (TBI). The inability to regenerate in CNS offers little hope for naturally repairing the damaged neurons. However, with the rapid development of new technologies, regenerative medicine offers great promises to patients with these disorders. Among many events for further advancement of regenerative medicine, extracellular matrix (ECM) plays a critical role for cellular migration and differentiation. To develop a biocompatible and electrically conductive substrate that can be potentially used to promote growth and regeneration of neurons and to record intracellular and multisite signals from brain as a probe, a polymeric precursor -SPR 220.7 was fabricated by pyrolysis at temperatures higher than 700 ºC. Human Neuroblastoma cells -SK-N-MC, SY5Y, mouse teratocarcinoma cells P-19 and rat PC12 cells were found to attach and proliferate on photoresist derived carbon film. Significantly, neuronal differentiation of PC12 cells induced by NGF was demonstrated by observing cell shape and size, and measuring the length of neurites under SEM. Our results indicated that fabricated carbon could potentially be explored in regenerative medicine for promoting neuronal growth and differentiation in CNS with neurodegeneration.
Aims
Limited data are available on the outcomes of cryoballoon ablation (CBA)‐based pulmonary vein isolation (PVI) for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The present study aimed to evaluate the safety and effectiveness of CBA in such patients.
Methods and results
Consecutive patients with AF referred for CBA‐based PVI from two highly experienced electrophysiology centres were included in this retrospective study. Of 651 patients undergoing CBA, 471 cases were divided into four groups: No HF (
n
= 255), HFpEF (
n
= 101), HFmrEF (
n
= 78), and HF with reduced ejection fraction (
n
= 37). Similar early recurrence of atrial arrhythmia was found among groups (16.2% vs. 15.4% vs. 14.9% vs. 12.2%,
P
= 0.798), and no significant difference of long‐term sinus rhythm (SR) maintenance was identified among the HFmrEF, HFpEF, and No HF groups (71.8% vs. 75.2% vs. 79.6%,
P
= 0.334). CBA is safe for patients with HFmrEF and HFpEF with similar complications compared with the No HF group (3.8% vs. 4.0% vs. 3.1%,
P
= 0.814). The reassessment of cardiac function after CBA showed that patients with HF indicated beneficial outcomes. Left atrial diameter (LAD) and left ventricular ejection fraction were significantly improved in the HFmrEF group. There were 41.6% of patients in the HFpEF group who were completely relieved from HF. LAD and New York Heart Association (NYHA) were associated with recurrence in the HFpEF and HFmrEF groups, and the maintenance of SR was an independent predictor of NYHA improvement for all HF groups.
Conclusions
Patients with HFmrEF and HFpEF could benefit from CBA with high SR maintenance and significant HF improvement.
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