Current neurovascular research
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The impact of hyperfibrinogenemia on short-term outcomes after acute ischemic stroke (AIS) is still not well understood. ⋯ In patients with AIS, hyperfibrinogenemia at the time of admission was independently associated with increased in-hospital mortality.
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Ununited peripheral nerves represent attractive site for connectivity with neuroprostheses because their predictable internal topography allows precise sorting of motor and sensory signals. Also transplantation of bone marrow mesenchymal stem cells (BMSCs) is increasingly recognized as an effective method of restore the peripheral nervous system injury due to its neuron-directed differentiation potential. This study was to evaluate the in vivo performance of BMSCs-packed Poly(3,4-ethylenedioxythiophene) (PEDOT) scaffolds across a critical nerve conduction gap and examine the potential mechanism by which BMSCs-packed PEDOT scaffolds mediate peripheral nerve regeneration in rat model of recurrent laryngeal nerve (RLN) deletion. ⋯ Meanwhile, both miR-21 overexpression and Notch pathway activation promote the expression of 6 nerve cell markers in BMSCs-directed neuron, whereas the inactivation of Notch pathway abrogates miR-21-inudced upregulation of 6 nerve cell markers. Moreover, knock-down of miR-21 suppresses the pro-neural restoration action of BMSCs-packed PEDOT scaffolds. In summary, our data suggested that BMSCs-packed PEDOT effectively repairs recurrent laryngeal nerve injury and the potential mechanism is miR-21- mediated Notch signal activation.
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Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. ⋯ In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.
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Oxaliplatin is a widely used chemotherapeutic agent that induces both acute and chronic peripheral neuropathy. Based on previous research indicating that estrogen replacement may attenuate some forms of pain in ovariectomized animals, we examined the effects of 17β-estradiol in OXAIPN. We discovered that local cold exposure induces an abnormal vascular response in both acute and chronic models of OXAIPN (oxaliplatin-induced peripheral neuropathy) that may be used as an easy and non-invasive method to predict which patients may be susceptible to the development of severe, chronic OXAIPN. ⋯ Local blockade of TRPA1 or TRPM8 receptors attenuated the initial vasodilation. Changes in release of calcitonin gene related peptide (CGRP) and nitric oxide (NO) metabolites due to local cold exposure at the hind paw were also involved. Administration of 17β-estradiol resulted in an anti-nociceptive effect and attenuating abnormal vasodilation.
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Mammalian forkhead transcription factors of the O class (FoxO) are exciting targets under consideration for the development of new clinical entities to treat metabolic disorders and diabetes mellitus (DM). DM, a disorder that currently affects greater than 350 million individuals globally, can become a devastating disease that leads to cellular injury through oxidative stress pathways and affects multiple systems of the body. ⋯ Furthermore, FoxO signaling can be dependent upon signal transduction pathways that include silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), Wnt, and Wnt1 inducible signaling pathway protein 1 (WISP1). Cellular metabolic pathways driven by FoxO proteins are complex, can lead to variable clinical outcomes, and require in-depth analysis of the epigenetic and post-translation protein modifications that drive FoxO protein activation and degradation.