This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.

Presenilin-1 (PSEN1) has been verified as an important causative factor for early onset Alzheimer’s disease (EOAD). PSEN1 is a part of γ-secretase, and in addition to amyloid precursor protein (APP) cleavage, it can also affect other processes, such as Notch signaling, β-cadherin processing, and calcium metabolism. Several motifs and residues have been identified in PSEN1, which may play a significant role in γ-secretase mechanisms, such as the WNF, GxGD, and PALP motifs. More than 300 mutations have been described in PSEN1; however, the clinical phenotypes related to these mutations may be diverse. In addition to classical EOAD, patients with PSEN1 mutations regularly present with atypical phenotypic symptoms, such as spasticity, seizures, and visual impairment. In vivo and in vitro studies were performed to verify the effect of PSEN1 mutations on EOAD. The pathogenic nature of PSEN1 mutations can be categorized according to the ACMG-AMP guidelines; however, some mutations could not be categorized because they were detected only in a single case, and their presence could not be confirmed in family members. Genetic modifiers, therefore, may play a critical role in the age of disease onset and clinical phenotypes of PSEN1 mutations. This review introduces the role of PSEN1 in γ-secretase, the clinical phenotypes related to its mutations, and possible significant residues of the protein.

Alzheimer’s disease (AD) is the most common cause of dementia. Although the heritability of AD is high, the knowledge of the disease-associated genes, their expression, and their disease-related pathways remain limited. Hence, finding the association between gene dysfunctions and pathological mechanisms, such as neuronal transports, APP processing, calcium homeostasis, and impairment in mitochondria, should be crucial. Emerging studies have revealed that changes in gene expression and gene regulation may have a strong impact on neurodegeneration. The mRNA–transcription factor interactions, non-coding RNAs, alternative splicing, or copy number variants could also play a role in disease onset. These facts suggest that understanding the impact of transcriptomes in AD may improve the disease diagnosis and also the therapies. In this review, we highlight recent transcriptome investigations in multifactorial AD, with emphasis on the insights emerging at their interface.

We report a novel fibrinogen variant (fibrinogen Seoul II), which has a heterozygous point mutation from CAA to CCA leading to A␣Gln328Pro. The mutation site is among several glutamine residues that serve as ␣-chain cross-linking acceptor sites. Fibrinogen Seoul II was found in a 51-year-old male patient and his family in Seoul, Korea. The patient was diagnosed with myocardial infarction at age 43. Eight years later he was admitted to the emergency room due to recurrence of the disease, where he expired under treatment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the patient's relatives, showed a decreased final turbidity, suggesting Seoul II fibrin clots are composed of thinner fibers. This supposition was verified using scanning electron microscopy. Alpha-polymer formation by the mutant fibrinogen upon thrombin treatment in the presence of factor XIII and calcium was distinctly impaired. This result confirms that the residue A␣328 plays a pivotal role in ␣ IntroductionFibrinogen, one of the critical plasma proteins, is a 340-kDa glycoprotein 1 synthesized in the liver 2,3 and has essential roles in both blood coagulation and platelet aggregation. 4 Fibrinogen is a dimer consisting of 2 identical pairs of A␣, B␤, and ␥ chains intertwined to form a trinodular molecule with 2 terminal D regions and a central E region. 5,6 The D region includes the carboxyl termini of the B␤ and ␥ chains, while that of the A␣ chain goes beyond the D region to form the ␣C domain, which is composed of residues A␣220-610 7 and normally interacts with the central E region.In the process of blood coagulation, thrombin cleaves fibrinopeptides A and B from A␣ and B␤ chains to form a fibrin monomer, exposing the GPR and GHRP sequences, respectively. Subsequently, protofibrils in a half-staggered array are formed, and the release of ␣C domains from the central E region is facilitated, allowing lateral aggregations through intermolecular associations between ␣C domains. 8,9 The final phase of fibrin clot formation involves the covalent modification of fibrin molecules by factor XIIIa. The factor XIIIa-mediated cross-linking process, where ␣-␣ cross-linking follows ␥-␥ cross-linking, contributes to stabilization of the fibrin clot and resistance to thrombolytic agents. 10,11 Until now, a variety of mutations in each of the fibrinogen chain genes have been reported in more than 350 families all over the world, with A␣-chain mutation as the most common form. 12 Those mutations usually have been associated with dysfibrinogenemia or hypofibrinogenemia, both of which feature decreased levels of plasma fibrinogen activity. Each A␣-chain has at least 2 glutamine acceptor sites located at amino acid residues 328 and 366 and 5 potential lysine donor sites between residues 518 and 584. 13 A␣ glutamine 328 is among several glutamine residues that serve as ␣-chain cross-linking acceptor sites, 10 for which only one fibrinogen variant has been described: compound heterozygotes characterized ...