Neonatal asphyxia is an important contributor to cerebral palsy (CP), for which there is no effective treatment to date. The administration of human cord blood cells (hUCBCs) is emerging as a therapeutic strategy for the treatment of neurological disorders. However, there are few studies on the application of hUCBCs to the treatment of neonatal ischemia as a model of CP. Experiments and behavioral tests (mainly motor tests) performed on neonatal hypoxia/ischemia have been limited to short-term effects of hUCBCs, but mechanisms of action have not been investigated. We performed a study on the use of hUCBCs in a rat model of neonatal hypoxia/ischemia and investigated the underlying mechanism for therapeutic benefits of hUCBC treatment. hUCBCs were intravenously transplanted into a rat model of neonatal hypoxia ischemia. hUCBCs increased microglia temporarily in the periventricular striatum in the early phase of disease, protected mature neurons in the neocortex from injury, paved the way for the near-normalization of brain damage in the subventricular zone (SVZ), and, in consequence, significantly improved performance in a battery of behavioral tests compared to the vehicle-treated group. Although the transplanted cells were rarely observed in the brain 3 weeks after transplantation, the effects of the improved behavioral functions persisted. Our preclinical findings suggest that the long-lasting positive influence of hUCBCs is derived from paracrine effects of hUCBCs that stimulate recovery in the injured brain and protect against further brain damage.
Genes can be divided into TATA-containing genes and TATA-less genes according to the presence of TATA box elements at promoter regions. TATA-containing genes tend to be stress-responsive, whereas many TATA-less genes are known to be related to cell growth or "housekeeping" functions. In a previous study, we demonstrated that there are striking differences among four gene sets defined by the presence of TATA box (TATA-containing) and essentiality (TATA-less) with respect to number of associated transcription factors, amino acid usage, and functional annotation. Extending this research in yeast, we identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways that are statistically enriched in TATA-containing or TATA-less genes and evaluated the possibility that the enriched pathways are related to stress or growth as reflected by the individual functions of the genes involved. According to their enrichment for either of these two gene sets, we sorted KEGG pathways into TATA-containing-gene-enriched pathways (TEPs) and essential-gene-enriched pathways (EEPs). As expected, genes in TEPs and EEPs exhibited opposite results in terms of functional category, transcriptional regulation, codon adaptation index, and network properties, suggesting the possibility that the bipolar patterns in these pathways also contribute to the regulation of the stress response and to cell survival. Our findings provide the novel insight that significant enrichment of TATA-binding or TATA-less genes defines pathways as stress-responsive or growth-related.
Aging is the result of a complex polygenetic trait characterized by decreased regeneration capacity and increased vulnerability to external and internal perturbations. Consequently, the inevitable process critically influences longevity, health, and disease susceptibility, ultimately leading to age-related pathologies and death. Gaining insights into inherent properties of aging and identifying definitive biomarkers and/or signatures are prerequisites for a better understanding and for the design of therapeutics for a wide range of age-related diseases that would improve the quality of life of the elderlies. However, a comprehensive understanding of the molecular mechanisms underlying aging has been hampered by its complex nature. Although the process has been subjected to substantial data-driven analyses including genomics, transcriptomics, and proteomics in a systemic manner, aging’s complexity hampers proper analysis as well as interpretation of the resulting outputs. Therefore, we review recent consequences focused on stem cell aging and age-related diseases.
Computational techniques for predicting interactions of proteins and druglike molecules have often been used to search for compounds that bind a given protein with high affinity. More recently, such tools have also been applied to the reverse procedure of searching protein targets for a given compound. Among methods for predicting protein–ligand interactions, ligand-based methods relying on similarity to ligands of known interactions are effective only when similar protein–ligand interactions are known. Receptor-based methods predicting protein–ligand interactions by molecular docking are effective only when high-accuracy receptor structures and binding sites are available. Moreover, the computational cost of molecular docking tends to be too high to be applied to the entire protein structure database. In this paper, an effective target prediction method, which combines ligand similarity-based and receptor structure-based approaches, is introduced. In this method, protein–ligand docking is performed after efficient structure- and similarity-based screening. The enriched protein target database by predicted binding ligands and sites allows detection of protein targets with previously unknown ligand interactions. The method, called GalaxySagittarius, is freely available as a web server at http://galaxy.seoklab.org/sagittarius.
Treating aged animals with plasma of an early developmental stage (e.g, umbilical cord plasma) showed an impressive potential to slow age-associated degradation of neuronal and cognitive functions. Translating such findings to clinical realities, however, requires effective ways for assessing treatment efficacy; ideal methods should be minimally invasive, amenable for serial assays, cost-effective, and quantitative.
Aging is defined broadly as the normal progressive process, consequently leading to growing vulnerability to disease and death. A major challenge lies in dissecting the underlying mechanisms of aging with conventional experiments due to the complexity of and multicontributions to the aging process, reflecting a need for investigation into it in various aspects. For this reason, the age process has currently been subjected to OMICS technologies including genomics, transcriptomics, proteomics, and metabolomics, allowing the exploration of age-related changes in a multifactorial manner. In addition, since age-dependent decline in stem cell function is almost identical to the biological age, stem cells have used to understand "aging" and to investigate key reverse factors for "antiaging". This suggests that a range of new approaches are needed to reveal the unknown biological basis for aging at a variety of different molecular levels using stem cells as a tool of normal aging process and can further apply fundamental aspects in biological aging and longevity.
Aging is an inevitable progressive decline in every physiological function and serves as a primary risk factor for cognitive decline and Alzheimer's disease. Thus, age-dependent impairments in cognitive function must be understood in association with general aging processes with an integrative approach in a systemic manner. An integrative aging gene network was constructed based on mutual molecular interactions using literature-curated interactome data and separated into functionally distinct modules. To investigate key surrogate biomarkers of the aging brain in the context of the general aging process, co-expression networks were built on post-mortem and Alzheimer's brain transcriptome data. In both the normal aging brain and the brain affected by Alzheimer's disease, the immune-related co-expression module was positively correlated with advancing age, whereas the synaptic transmission-related co-expression module was decreased with age. Importantly, the network topology-based analysis indicated that complement system genes were prioritized as a surrogate biomarker in evaluating the process of brain aging. Our public data-centered analysis coupled with experimental validation revealed that the complement system is likely to be a master regulator in initiating and regulating the immune system in the aging brain and could serve as reliable and surrogate biomarkers for the diagnosis of cognitive dysfunction.
도심지 근접시공 발파에는 진동 소음에 따른 민원의 문제가 주요시된다. 발파 진동 소음을 줄이기 위해 최근에 국내에 도입된 전자뇌관을 사용하여 데크차지 공법에 적용하면 cut off 등과 같은 현상이 없어져서 안전한 시공이 가능하고, 또한 수평방향으로 발파가 가능해져서 대규모 발파가 가능해진다. 본 연구에서는 전자뇌관을 사용한 수평방향데크차지 공법의 효율을 기존 공법의 것과 비교해보고, 현장적용 가능성을 평가해보았다. 그 결과 발파 진동 소음과 2차 파쇄량의 감소를 확인하였고, 뿐만 아니라 전반적으로 발파 효율이 증가하여 진동 규제 기준치 내에서 대규모 발파가 가능함을 확인하였다. In close to downtown construction, the main problem is complaints caused by blasting vibration and noise. To reduce blasting vibration and noise, deck-charge blasting method using electronic detonator can be more secure because there is no cut-off problem. And in this method it is possible to blast in horizontal direction. In this study, the efficiency of horizontal direction deck-charge blasting method using electronic detonator is compared to that of the existing blasting method. And the possibility of applying the construction site is evaluated. As a result, the reduction of blasting vibration, noise and secondary breaking has been determined, as well as large-scale blasting in the vibration criterion can be regulated by the overall increase in blasting efficiency.
Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs. The AMSCs transplanted into the ischemic rat model of stroke dramatically inhibited the expression of pro-inflammatory cytokines and up-regulated CD200, as compared with the levels in the sham-treated group. Moreover, decreased microglia activation in the boundary region and improvements in behavior were confirmed in AMSC-treated ischemic rats. The results suggested that the highly expressed CD200 from the AMSCs in a hypoxic environment modulates levels of inflammatory cytokines and microglial activation, thus increasing the therapeutic recovery potential after hypoxic-ischemic brain injury, and further demonstrated the immunomodulatory function of AMSCs in a stroke model. Stem cells derived from the human placenta offer therapeutic promise in reducing the brain inflammation associated with stroke. Recently, there has been considerable focus on treating the acute brain inflammation seen in stroke patients, and stem cells have gained attention as potential therapeutic agents due to their ability to suppress immune responses. Using a rat model of stroke, a team headed by Jisook Moon at CHA University in Gyeonggi-do, Korea, investigated how placental stem cells regulated the immune responses that occur following brain cell death and subsequent inflammation. The team found that CD200 (an anti-inflammatory factor) is a key molecule in the beneficial effects of stem cells in the early phase of stroke. The authors conclude that placental stem cells have great potential in effectively treating inflammation-related diseases.
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