Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.
Enteric duplication is rare in dogs. Here, we report the rarest form of duplication in which two segments are parallel and share a wall for most of their lengths. A nine-year-old spayed female Yorkshire terrier was referred to the Veterinary Medical Teaching Hospital at Gyeongsang National University due to anorexia and diarrhoea. Physical examination, haematological examination, radiography, and ultrasonography were performed. On physical examination, dry, pale mucous membrane was identified. Moderate anaemia with decreased packed cell volume was detected in complete blood count. Serum urea nitrogen and creatinine levels were mildly increased. Radiographic images revealed no significant findings. On ultrasonographic examination, a multi-layered appearance of a focal small intestinal segment was identified in the left mid abdomen. Following the lesion, it was divided into two small intestinal segments. Based on imaging findings, intussusceptions or enteric duplication were suspected. To resect the abnormal small intestinal segment, enterectomy was performed. Follow-up was not performed because the patient expired during the postoperative recovery time. The histopathological diagnosis was non-communicating small intestinal duplication. Non-communicating intestinal duplication is related to embryologic abnormalities and is usually concurrent with other anomalies such as vertebral malformations and urogenital duplications. However, this case had no other anomalies associated with the malformation of the intestine.
It is commonly accepted that the sustained release of bone morphogenetic protein-2 (BMP-2) can enhance bone regeneration and minimize its safety issues. However, little is known regarding the appropriate duration of BMP-2 stimulation for sufficient osteogenic differentiation and new bone formation because of the short half-life of BMP-2 in the physiological environment and the lack of a well-defined delivery matrix that can regulate the release period of BMP-2. In this study, we prepared porous poly(lactic-co-glycolic acid) (PLGA) beads with different surface pore sizes that can regulate the release period of BMP-2 (i.e., 7, 17, and 30 days) while providing the BMP-2 concentration required for bone regeneration. Our findings in both in vitro cell culture and in vivo animal studies using these BMP-2-loaded beads demonstrate that release of BMP-2 within 7 days affects only the initial differentiation of human periosteum-derived cells (hPDCs) and does not significantly enhance their subsequent differentiation into mature functional cells. However, extending the duration of BMP-2 stimulation over 17 days can provide a suitable environment for osteogenic differentiation of hPDCs and new bone formation.
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