Involvement of RNA helicase p68 in skin wound healing process in rats

Purpose: RNA helicase p68 plays an important role in organ development and maturation through tuning cell proliferation. However, the character and role of p68 in the whole wound healing process need more study. Methods: First, we characterize expression of p68 in normal rat skin development postnatal. Then, we assayed dynamic change of p68 in rat skin from different stage after injury, and explored the role of p68 in proliferation and migration of three types of wound healing related cells. Results: p68 was down-regulated during skin developmental and maturation process, up-regulated after wound, peaked on day 14 and then significantly decreased. Wound fluid enhanced wound healing related cell proliferation and up-regulated expression of p68. Conversely, reducing p68 expression by RNA interference resulted in significantly slower proliferation and migration. Conclusion: Our results define an important role of RNA helicase p68 in skin wound healing process.     

Newly developed strategies for multifunctional mitochondria-targeted agents in cancer therapy

The development of multifunctional agents that could be used for simultaneous tumor targeting, imaging and treatment is a major goal in cancer research and is expected to contribute significantly to the realization of personalized oncology. Mitochondria are involved in diverse physiological activities and confer vital roles in cancer development and progression. Increasing efforts are being made to develop cancer treatment strategies based on various mitochondrial targets and novel mitochondrial drug delivery systems. Multifunctional nanostructures or multifunctional chemical compounds further broaden the current concept of tumor targeting and provide alternative solutions for mitochondrially targeted cancer therapy.     

Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord

Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450 μm (n = 19) or 660 μm in diameter (n = 14). Animals were sacrificed after 1, 2 and 3 months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450 μm scaffolds had significantly greater axon fibers per channel at the 1 month (186 ± 37) and 3 month (78 ± 11) endpoints than the 660 μm scaffolds (90 ± 19 and 40 ± 6, respectively) (p = 0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660 μm channels was most pronounced at the 1 month endpoint, at 28,046 ± 6551 and 58,633 ± 7063 μm², respectively (p = 0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.     

Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3-phosphoinositides

Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34⁺ and CD41⁺ cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation-induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3-kinase (PI3K), ERK1/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1-orchestrated activation of ERK1/2 and Akt signaling.     

Dopamine induces platelet production from megakaryocytes via oxidative stress-mediated signaling pathways

Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis.     

乳酸-羟基乙酸共聚物多肽蛋白类药物微球控释系统的突释与控制

背景：突释问题是限制多肽蛋白类微球广泛应用的一个关键技术问题,已经成为PLGA微球控释系统面临的一个亟待解决的问题。 目的：分析近年来国内外对乳酸-羟基乙酸共聚物多肽蛋白类药物微球的突释与控制的研究,对突释的原因、影响突释的因素以及减少突释的方法与措施进行了详细的介绍。 方法：应用计算机检索CNKI和PubMed数据库中1999-01/2010-12关于乳酸-羟基乙酸共聚物多肽蛋白类药物微球控释系统研究的文章,在标题和摘要中以“聚乳酸-羟基乙酸;多肽;蛋白;微球;突释;控制”或“PLGA; peptide; protein ; microspheres; burst release; control”为检索词进行检索。通过阅读标题和摘要进行初选,排出较陈旧和重复研究文献,保留符合纳入标准的文献24篇。 结果与结论：对乳酸-羟基乙酸共聚物多肽蛋白类药物微球突释机制的理解,可以更好地实现对微球突释的控制,以扩大多肽蛋白类药物在临床上的应用。PLGA的性质、微球的制备方法、微球的制备参数都在不同程度上影响微球的突释,并且可能是多因素协同作用。通过对上述各种因素加以适当控制,可在一定程度上减少微球的突释率。通过该方面的机制研究对指导新药开发具有重要意义。     

乳酸-羟基乙酸共聚物多肽蛋白类药物微球控释系统的突释与控制

背景：突释问题是限制多肽蛋白类微球广泛应用的一个关键技术问题,已经成为PLGA微球控释系统面临的一个亟待解决的问题。 目的：分析近年来国内外对乳酸-羟基乙酸共聚物多肽蛋白类药物微球的突释与控制的研究,对突释的原因、影响突释的因素以及减少突释的方法与措施进行了详细的介绍。 方法：应用计算机检索CNKI和PubMed数据库中1999-01/2010-12关于乳酸-羟基乙酸共聚物多肽蛋白类药物微球控释系统研究的文章,在标题和摘要中以“聚乳酸-羟基乙酸;多肽;蛋白;微球;突释;控制”或“PLGA; peptide; protein ; microspheres; burst release; control”为检索词进行检索。通过阅读标题和摘要进行初选,排出较陈旧和重复研究文献,保留符合纳入标准的文献24篇。 结果与结论：对乳酸-羟基乙酸共聚物多肽蛋白类药物微球突释机制的理解,可以更好地实现对微球突释的控制,以扩大多肽蛋白类药物在临床上的应用。PLGA的性质、微球的制备方法、微球的制备参数都在不同程度上影响微球的突释,并且可能是多因素协同作用。通过对上述各种因素加以适当控制,可在一定程度上减少微球的突释率。通过该方面的机制研究对指导新药开发具有重要意义。     

Analysis of histopathological aspects and bone destruction characteristics in acquired middle ear cholesteatoma of pediatric and adult patients

ObjectiveThe aim of this study was to investigate the proliferative and apoptotic activity of middle ear cholesteatoma in pediatric and adult patients, in addition to comparing its histopathological aspects and the severity of advanced bone destruction.Materials and methodsMedical records of 223 patients treated for chronic otitis media with cholesteatoma at the Otolaryngology Department of Dokuz Eylul University between January 1992 and December 2013 were retrospectively evaluated. Sixty-one patients subjected to tympanomastoidectomy due to middle ear cholesteatoma, with sufficient specimens for histopathological examination, were included in the study. Sections of archived tissues in paraffin blocks were subjected to new histopathological examinations. The proliferative and apoptotic activities of cholesteatoma were determined by immunohistochemical staining for epithelial thickness (ET), and Ki-67 and caspase-3 expression. A novel scoring system, the Bone Erosion Score (BES), was developed to estimate the severity of bone destruction. The Austin–Kartush classification score (AKCS) was also calculated.ResultsET and Ki-67 expression was higher in adult patients than in the pediatric patients (p = 0.009 and 0.01, respectively); however, caspase-3 immunopositivity did not show any significant intergroup differences (p = 0.106). The differences in AKCS and BES between pediatric and adult patients were not statistically significant. According to the correlation analysis, a significant positive correlation was observed between AKCS and BES (p = 0.001), and between ET and Ki-67 expression (when histopathological data were compared) (p = 0.001).ConclusionThe proliferative activity of cholesteatoma was higher in adult patients. Therefore, these findings do not support the theory that the aggressive clinical course of cholesteatoma in pediatric patients is correlated with its histopathological characteristics.