Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Given this observation, we performed a random screening of a chemical library and identified 3 compounds (JH1, JH4, and JH13) that efficiently block progerin-lamin A/C binding. These 3 chemicals, particularly JH4, alleviated nuclear deformation and reversed senescence markers characteristic of HGPS cells, including growth arrest and senescence-associated β-gal (SA-β-gal) activity. We then used microarray-based analysis to demonstrate that JH4 is able to rescue defects of cell-cycle progression in both HGPS and aged cells. Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan. Together, these findings indicate that specific inhibitors with the ability to block pathological progerin-lamin A/C binding may represent a promising strategy for improving lifespan and health in both HGPS and normal aging.
The tumor suppressor, p53, plays an essential role in the cellular response to stress through regulating the expression of genes involved in cell cycle arrest, apoptosis and autophagy. Here, we used a cell-based reporter system for the detection of p53 response transcription to identify the marine sponge metabolites, ilimaquinone and ethylsmenoquinone, as activators of the p53 pathway. We demonstrated that ilimaquinone and ethylsmenoquinone efficiently stabilize the p53 protein through promotion of p53 phosphorylation at Ser15 in both HCT116 and RKO colon cancer cells. Moreover, both compounds upregulate the expression of p21WAF1/CIP1, a p53-dependent gene, and suppress proliferation of colon cancer cells. In addition, ilimaquinone and ethylsmenoquinone induced G2/M cell cycle arrest and increased caspase-3 cleavage and the population of cells that positively stained with Annexin V-FITC, both of which are typical biochemical markers of apoptosis. Furthermore, autophagy was elicited by both compounds, as indicated by microtubule-associated protein 1 light chain 3 (LC3) puncta formations and LC3-II turnover in HCT116 cells. Our findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by activation of the p53 pathway and may have significant potential as chemo-preventive and therapeutic agents for human colon cancer.
Areas associated with PD were activated by the acupuncture stimulation on GB34. This shows that acupuncture treatment on GB34 may be effective in improving the symptoms of PD. Although more randomized controlled trials on the topic will be needed, this study shows that acupuncture may be helpful in the treatment of symptoms involving PD.
BackgroundThe publication rate of presentations at medical international meetings has ranged from 11% to 78% with an average of 45%. To date, there are no studies about the final rate of publications at scientific meetings associated with plastic surgery from Korea. The present authors investigated the publication rate among the presentations at meetings associated with plastic surgery.MethodsThe titles and authors of the abstracts from oral and poster presentations were collected from the program books of the Congress of the Korean Society of Plastic and Reconstructive Surgeons (CKSPRS) for 2005 to 2007 (58th-63rd). All of the abstracts presented were searched for using PubMed, KoreaMed, KMbase, and Google Scholar. The titles, key words from the titles, and the authors' names were then entered in database programs. The parameters reviewed included the publication rate, type of presentation including running time, affiliation, subspecialty, time to publication, and publication journal.ResultsA total of 1,176 abstracts presented at the CKSPRS from 2005 to 2007 were evaluated. 38.7% of the abstracts, of which oral presentations accounted for 41.0% and poster presentations 34.8%, were published as full papers. The mean time to publication was 15.04 months. Among journals of publication, the Journal of the Korean Society of Plastic and Reconstructive Surgeons was most used.ConclusionsBrilliant ideas and innovative approaches are being discussed at CKSPRS. The 38.7% publication rate found from this research appeared a bit lower than the average rate of medical meetings. If these valuable presentations are not available as full papers, the research would be a waste of time and effort.
Recently, diagnoses of and operations for medial orbital blowout fracture have increased because of the development of imaging technology. In this article, the authors review the literature, and overview the accumulated knowledge about the orbital anatomy, fracture mechanisms, surgical approaches, reconstruction materials, and surgical methods. In terms of surgical approaches, transcaruncular, transcutaneous, and transnasal endoscopic approaches are discussed. Reconstruction methods including onlay covering, inlay implantation, and repositioning methods are also discussed. Consideration and understanding of these should lead to more optimal outcomes.
BackgroundReconstruction of combined orbital floor and medial wall fractures with a comminuted inferomedial strut (IMS) is challenging and requires careful practice. We present our surgical strategy and postoperative outcomes.MethodsWe divided 74 patients who underwent the reconstruction of the orbital floor and medial wall concomitantly into a comminuted IMS group (41 patients) and non-comminuted IMS group (33 patients). In the comminuted IMS group, we first reconstructed the floor stably and then the medial wall by using separate implant pieces. In the non-comminuted IMS group, we reconstructed the floor and the medial wall with a single large implant.ResultsIn the follow-up of 6 to 65 months, most patients with diplopia improved in the first-week except one, who eventually improved at 1 year. All patients with an EOM limitation improved during the first month of follow-up. Enophthalmos (displacement, 2 mm) was observed in two patients. The orbit volume measured on the CT scans was statistically significantly restored in both groups. No complications related to the surgery were observed.ConclusionsWe recommend the reconstruction of orbit walls in the comminuted IMS group by using the following surgical strategy: usage of multiple pieces of rigid implants instead of one large implant, sequential repair first of the floor and then of the medial wall, and a focus on the reconstruction of key areas. Our strategy of step-by-step reconstruction has the benefits of easy repair, less surgical trauma, and minimal stress to the surgeon.
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