Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits

Cognitive Informatics

Cognitive Informatics (CI) is a contemporary field of basic studies on the brain, computational intelligence theories and underpinning denotational mathematics. Its applications include cognitive systems, cognitive computing, cognitive machine learning and cognitive robotics. IEEE ICCI*CC'17 on Cognitive Informatics and Cognitive Computing was focused on the theme of neurocomputation, cognitive machine learning and brain-inspired systems. This paper reports the plenary panel (Part I) at IEEE ICCI*CC'17 held at Oxford University. The summary is contributed by invited keynote speakers and distinguished panelists who are part of the world's renowned scholars in the transdisciplinary field of CI and cognitive computing

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Bacillus cereus group strains, their hemolysin BL activity, and their detection in foods using a 16S RNA and hemolysin BL gene-targeted multiplex polymerase chain reaction system

Hemolysin BL (HBL) is a major virulence factor for Bacillus cereus group strains. It is also a target enterotoxin for the most commonly used B. cereus detection kit, i.e., the B. cereus enterotoxin (diarrheal type) reversed passive latex agglutination (BCET-RPLA) test kit. A survey of the HBL activities and the cytotoxicities to the Chinese hamster ovary (CHO) cells for the B. cereus group strains, however, showed that although only part of the B. cereus group strains are HBL active, all strains show cytotoxicity to the CHO cells. Thus, methods that allow the detection of not only the HBL but also of the B, cereus group strains are important. In this study, by comparison of the gene sequences of the 16S rRNA for B. cereus group and other bacteria strains, we designed primers B16S1 and B16S2 specific to all the B. cereus group strains. In addition, because HBL is a major enterotoxin, we also designed HBL gene-specific polymerase chain reaction (PCR) primers, i.e., Hm1 and Hm2, that generated the same results as those of the hemolysis and BCET-RPLA assays. Primers B16S1/B16S2 and Hm1/Hm2 could be combined into a multiplex PCR system for the simultaneous detection of B. cereus group cells and the possible presence of their HBL enterotoxins. Also, all these PCR systems allowed the detection of n x 10(0) CFU B. cereus cells per g of food sample if an 8-h enrichment step was performed prior to the PCR

The Role of Endoplasmic Reticulum Stress-Related Unfolded Protein Response in the Radiocontrast Medium-Induced Renal Tubular Cell Injury

Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of CM-induced nephropathy. CM has been shown to affect the endoplasmic reticulum (ER) related capacity. Unfolded protein response (UPR) is known as a prosurvival response to reduce the accumulation of unfolded proteins and restore normal ER function. However, the role of ER stress related UPR in the CM-induced renal cell injury still remains unclear. In this study, we examined whether UPR participates in urografin (an ionic CM)-induced renal tubular cells apoptosis. Treatment with urografin in normal rat renal tubular cell line (NRK52E) markedly increased cell apoptosis and decreased cell viability with a dose- and time-dependent manner. The cell necrosis was not increased in urografin-treated cells. Urografin also enhance the induction of ER stress related markers in NRK52E cells, including glucose-regulated protein (GRP)78 and GRP94 expressions, procaspase-12 cleavage, phosphorylation of PERK (PKR [double-stranded RNA activated protein kinase]-like ER kinase), and eukaryotic initiation factor 2 alpha (eIF2 alpha). Salubrinal, a selective inhibitor of eIF2 alpha dephosphorylation, effectively decreased urografin-induced cell apoptosis. Furthermore, transfection of GRP78-small interfering RNA in NRK52E cells significantly enhanced urografin-induced cell apoptosis. These results suggest that GRP78/eIF2 alpha-related signals play a protective role during UPR, and the activation of ER stress related UPR may play an important regulative role in urografin-induced renal tubular injury

Quality-of-life outcomes after Gamma Knife surgery for trigeminal neuralgia

Object. Gamma Knife surgery (GKS) is an important part of the neurosurgical armamentarium for treatment of patients with trigeminal neuralgia (TN) and is regarded as the first-line treatment in patients with TN who have serious medical comorbidities. In this study, the authors investigated the efficacy of GKS on TN in patients with serious medical comorbidities. Methods. Between May 2004 and September 2007,52 severely ill patients who also had TN with Barrow Neurological Institute (BNI) facial pain scores of IV or V were entered into this study. The patients' medical records and imaging findings ere reviewed by an anesthesiologist and neurosurgeons to determine whether GKS was a reasonable approach to palliate the patient's pain. All patients underwent GKS, in which a maximum dose of 80 Gy was targeted to the trigeminal nerve with or without plugging to keep the dose received by the brainstem at less than 16 Gy. After treatment, every patient had clinical follow-up every 1-3 months and filled out questionnaires designed to assess BNI facial pain and numbness scores, visual analog scale scores, and 36-Item Short Form Health Survey (SF-36) scores every 3 months until the end of the study. Statistical analysis was performed to find favorable prognostic factors related to pain relief and changes in quality of life. Results. The median age of the patients was 71 years, and the male/female ratio was 30:22. The median followup period was 54 months (at least 2 years). All patients had a positive initial response to GKS, with BNI facial pain scores at least 1 point less than respective pre-GKS scores. Three patients (5.7%) obtained BNI facial pain Score I. Twenty-three patients (44.2%) experienced pain recurrence at a median follow-up of 33 months. One patient suffered from angina and required time in an intensive care unit; another patient had bleeding from a pin wound that required suturing. Alterations in BNl scores were highly correlated to visual analog scale scores (R(2) = 0.978). In both univariate and multivariate analyses, a decreased BN1 facial pain score at different time points was significantly (p < 0.05) related to younger patient age, no previous treatment, evidence of vessel compression on MR imaging, time of first GKS <= 24 month, physical function (SF-36), role limitation due to a physical problem (SF-36), role limitation due to an emotional problem (SF-36), mental health (SF-36), social functioning (SF-36), bodily pain (SF-36), and general health (SF-36), but was not related to vitality (SF-36). Five patients (9.6%) experienced facial numbness at a mean of 13.2 +/- 3.1 months after GKS (4 patients with BNI facial numbness Score II and 1 with BNI facial numbness Score Ill). Post-GKS W. imaging changes, including focal contrast enhancement or T2-weighted signal alterations, were identified in 3 patients (5.7%). Conclusions. Gamma Knife surgery produced significant pain relief in severely ill patients who had TN without causing appreciable morbidity. The effect of reduced pain significantly paralleled an improvement in SF-36 quality-of-life indices. (DOI: 10.3171/2010.8.GKS10879

Potentiation of angiogenesis and regeneration by G-CSF after sciatic nerve crush injury

Granulocyte Colony-Stimulating factor (G-CSF) demonstrates neuroprotective effects through different mechanisms, including mobilization of bone marrow cells. However, the influence of G-CSF-mediated mobilization of bone marrow-derived cells on injured sciatic nerves remains to be elucidated. The administration of G-CSF promoted a short-term functional recovery 7 days after crush injury in sciatic nerves. A double-immunofluorescence study using green fluorescent protein-chimeric mice revealed that bone marrow-derived CD34+ cells were predominantly mobilized and migrated into injured nerves after G-CSF treatment. G-CSF-mediated beneficial effects against sciatic nerve injury were associated with increased CD34+ cell deposition, vascular endothelial growth factor (VEGF) expression, and vascularization/angiogenesis as well as decreased CD68+ cell accumulation. However, cell differentiation and VEGF expression were not demonstrated in deposited cells. The results suggest that the promotion of short-term functional recovery in sciatic nerve crush injury by G-CSF involves a paracrine modulatory effect and a bone marrow-derived CD34+ cell mobilizing effect. (C) 2009 Elsevier Inc. All rights reserved

Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol suppresses high glucose-induced human endothelial cell apoptosis

Angiopathy is a major complication of diabetes. Abnormally high blood glucose is a crucial risk factor for endothelial cell damage. Nuclear factor-kappa B (NF-kappa B) has been demonstrated as a mediated signaling in hyperglycemia or oxidative stress-triggered apoptosis of endothelial cells. Here we explored the efficacy of honokiol, a small molecular weight natural product, on NADPH oxidase-related oxidative stress-mediated NF-kappa B-regulated signaling and apoptosis in human umbilical vein endothelial cells (HUVECs) under hyperglycemic conditions. The methods of morphological Hoechst staining and annexin V/propidium iodide staining were used to detect apoptosis. Submicromolar concentrations of honokiol suppressed the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22(phox) protein expression, and reactive oxygen species production in high glucose (HG)-stimulated HUVECs. The degradation of I kappa B alpha and increase of NF-K beta activity were inhibited by honokiol in HG-treated HUVECs. Moreover, honokiol (0.125-1 mu M) also suppressed HG-induced cyclooxygenase (COX)-2 upregulation and prostaglandin E(2) production in HUVECs. Honokiol could reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by HG. These results imply that inhibition of NADPH oxidase-related oxidative stress by honokiol suppresses the HG-induced NF-kappa B-regulated COX-2 upregulation, apoptosis, and cell death in HUVECs, which has the potential to be developed as a therapeutic agent to prevent hyperglycemia-induced endothelial damage. (C) 2008 Elsevier Inc. All rights reserved

Recruitment by SDF-1 alpha of CD34-positive cells involved in sciatic nerve regeneration

Object. Increased integration of CD34(+) cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34(+) cells. SDF-1 alpha and its receptor mediate the recruitment of CD34(+) cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34(+) cell recruitment triggered by SDF-1 alpha and the involvement of CD34(+) cells in peripheral nerve regeneration. Methods. Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1 alpha recombinant proteins; and Group 3, crush injury and local application of SDF-1 alpha antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2,3, and 4 weeks after injury. The expression of SDF-1 alpha, accumulation of CD34(+) cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1,3,7,10,14,21, and 28 days after injury. Results. Application of SDF-1 alpha increased the migration of CD34(+) cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1 alpha, with a peak of 10-14 days postinjury, and this increased expression of SDF-1 alpha paralleled the deposition of CD34(+) cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1 alpha recombinant protein and abolished by administration of SDF-1 alpha antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve. Conclusions. Expression of SDF-1 alpha facilitates recruitment of CD34(+) cells in peripheral nerve injury. The increased deposition of CD34(+) cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1 alpha for enhancing the recruitment of CD34(+) cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders. (DOI: 10.3171/2011.3.JNS101582