Cell-based therapy could aid in alleviating symptoms or even reversing the progression of neurodegenerative diseases and nerve injuries. Fibroblast growth factor 1 (FGF1) has been shown to maintain the survival of neurons and induce neurite outgrowth. Accumulating evidence suggests that combination of FGF1 and cell-based therapy is promising for future therapeutic application. Neural stem cells (NSCs), with the characteristics of self-renewal and multipotency, can be isolated from embryonic stem cells, embryonic ectoderm, and developing or adult brain tissues. For NSC clinical application, several critical problems remain to be resolved: (1) the source of NSCs should be personalized; (2) the isolation methods and protocols of human NSCs should be standardized; (3) the clinical efficacy of NSC transplants must be evaluated in more adequate animal models; and (4) the mechanism of intrinsic brain repair needs to be better characterized. In addition, the ideal imaging technique for tracking NSCs would be safe and yield high temporal and spatial resolution, good sensitivity and specificity. Here, we discuss recent progress and future development of cell-based therapy, such as NSCs, induced pluripotent stem cells, and induced neurons, in neurodegenerative diseases and peripheral nerve injuries.
Structure, Function and Regulation of the Hsp90 Machinery
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Jing Li, Johannes Buchner DOI:10.4103/2319-4170.113230 PMID:23806880
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
G-protein-Coupled Receptors and Their (Bio) Chemical Significance Win 2012 Nobel Prize in Chemistry
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Hsi-Hsien Lin DOI:10.4103/2319-4170.113233 PMID:23806881
G-protein-coupled receptors (GPCRs) are seven transmembrane cell surface proteins specialized in cellular communication. These receptors represent a major gateway through which cells convert external cues into intracellular signals and respond with appropriate actions. While the effects of hormones, neurotransmitters, and drugs on cells, tissues, organs, and even whole organisms are well described, the molecular identity of the direct targets and the diverse signaling mechanisms of these biological ligands have been slow and hard to define. The Nobel Prize in Chemistry for the year 2012 acknowledges the importance of GPCRs in these processes, especially for the contribution of Profs Robert J. Lefkowitz and Brian K. Kobilka to the studies of GPCRs. In this brief review, the seminal works accomplished by the two GPCR pioneers are summarized and the (bio) chemical significance of GPCRs in health and disease is discussed.
Background: General anesthesia is used for most major surgeries, and the most common side effects include headache, nausea, vomiting, and sore throat. Major breast surgery is associated with a high incidence of postoperative nausea and vomiting (PONV). We compared the postoperative nausea and vomiting of propofol-based total intravenous anesthesia (TIVA) and sevoflurane (SEVO) anesthesia under auditory evoked potential (AEP) monitoring in female patients undergoing breast surgery.
Methods: A total of 84 patients scheduled to undergo elective breast surgery from 1 to 4 h in duration from March 2011 to December 2011 were prospectively included in the study. All participants were randomly assigned to TIVA or SEVO group. The AEP index was maintained at 15-25. After completing the surgery, the duration of surgery, emergence time, and the side effects of PONV were recorded.
Results: Patient characteristics, intraoperative and postoperative data, and the amounts of intraoperative analgesic drugs used were not significantly different between the TIVA and SEVO groups. The incidence of PONV was significantly higher in the SEVO group than in the TIVA group (50% and 14.3%, respectively; p < 0.001), and the total cost was significantly lower in the TIVA group than in the SEVO group (648 ± 185 and 850 ± 197, respectively).
Conclusion: We observed that when compared with sevoflurane, propofol given for the maintenance of general anesthesia improves the postoperative patient well-being and reduces the incidence of PONV. Furthermore, total intravenous anesthesia with propofol resulted in significant cost reductions.
Background: Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) have previously been found to be reduced in the prefrontal cortex of patients with schizophrenia. In this study, we tried to investigate the protein levels of BDNF and TrkB from peripheral blood in the veins of individuals with schizophrenia and health controls.
Methods: From January 2008 to November 2010, we recruited 40 schizophrenic patients and 56 healthy controls. Serum BDNF and total TrkB protein levels were detected with enzyme-linked immunosorbent assay (ELISA) kits. Outliners of BDNF and TrkB were excluded initially. Analysis of covariance (ANCOVA) with age adjustment was used for group mean differences of different groups.
Results: After using the ANCOVA with age adjustment, the results of this work showed that BDNF presented no significant difference (F = 0.065, p = 0.800), but the serum TrkB protein level was significantly lower in schizophrenic patients than in healthy controls (F = 8.34, p = 0.005).
Conclusion: Our findings showed a lower TrkB protein level in serum from schizophrenia patients compared with healthy controls, indicating that the signaling transmission of BDNF/TrkB may be affected in peripheral blood from individuals with schizophrenia.
Plasma P-selectin Predicts Long-term Cardiovascular Events in Hospitalized Patients with Suspected Coronary Artery Disease and Preserved Left Ventricular Function: A 10-Year Follow-Up Study
Background: A variety of biomarkers have been investigated on their values to predict cardiovascular outcomes, such as high-sensitivity C-reactive protein (hs-CRP), fibrinogen, troponin-I (TnI), and soluble P-selectin (sP-sel). By a design of head-to-head comparison, this study sought to figure out the long-term prognostic values of these parameters in patients hospitalized with suspected coronary artery disease.
Methods: A total of 170 patients hospitalized with suspected coronary artery disease were enrolled and followed up for an average of 10 years. sP-sel, hs-CRP, TnI, and fibrinogen levels were measured. During the follow-up period, cardiac events were recorded including cardiac death, non-fatal myocardial infarction, and acute coronary syndromes with hospitalization.
Results: For all 170 patients, with a median follow-up time of 9.86 ± 3.87 years, no parameter was able to significantly predict the occurrence of cardiac events. In subgroup analysis, an sP-sel of ≥ 63.5 ng/ml significantly predicted the development of all composite cardiac events only in patients with a left ventricular ejection fraction > 50% (n = 94, p = 0.04). However, the levels of hs-CRP, TnI, and fibrinogen did not have significant predictive values. Multivariate analysis also demonstrated the independent predictive value of sP-sel on all cardiac events (hazard ratio = 5.82, p = 0.02). All parameters, including sP-sel, could not demonstrate prognostic values in patients with a left ventricular ejection fraction ≤ 50% (n = 76).
Conclusions: In this 10-year long-term follow-up study, sP-sel was demonstrated to have prognostic values in predicting the cardiac events in patients with preserved left ventricular systolic function.
Background: In Taiwan, the prevalence of head and neck cancer is relatively high. Because radiation-associated carotid stenosis is a significant risk factor for stroke, carotid artery stenting (CAS), instead of carotid endarterectomy, is indicated in patients with radiation-associated carotid stenosis. We sought to evaluate the effect of neck radiotherapy (XRT) on the long-term outcome of patients undergoing CAS.
Methods: From March 2001 to November 2011, 147 CAS procedures were performed on 129 patients (n = 43 for XRT, n = 86 for non-XRT). Mean follow-up was 42.7 ± 20.5 months (median: 52 months; range: 1-60 months). Duplex velocity criterion for > 50% restenosis after CAS was defined as peak systolic velocity > 175 cm/s. Endpoints included 5-year freedom from mortality, ipsilateral recurrent stroke, and major adverse cardiovascular events (MACE).
Results: The mean age of XRT patients was significantly lesser than that of non-XRT patients (61 ± 8 vs. 71 ± 8, p < 0.001). There was significantly less coronary artery disease and other cardiovascular co-morbidities in XRT patients. No significant differences were noted in the composite 30-day ipsilateral stroke/myocardial infarction/mortality (XRT: 8.6% vs. non-XRT: 6%, p > 0.05) and 5-year freedom from mortality, ipsilateral recurrent stroke, and MACE (p > 0.05) between the two groups. Intra-stent carotid restenosis > 50% was significantly higher in the XRT group on follow-up.
Conclusion : Long-term outcomes of CAS for radiation-associated stenosis were not altered by a history of neck XRT, except for asymptomatic carotid restenosis.