Drug repositioning of polaprezinc for bone fracture healing.

Fractures and related complications are a common challenge in the field of skeletal tissue engineering. Vitamin D and calcium are the only broadly available medications for fracture healing, while zinc has been recognized as a nutritional supplement for healthy bones. Here, we aimed to use polaprezinc, an anti-ulcer drug and a chelate form of zinc and L-carnosine, as a supplement for fracture healing. Polaprezinc induced upregulation of osteogenesis-related genes and enhanced the osteogenic potential of human bone marrow-derived mesenchymal stem cells and osteoclast differentiation potential of mouse bone marrow-derived monocytes. In mouse experimental models with bone fractures, oral administration of polaprezinc accelerated fracture healing and maintained a high number of both osteoblasts and osteoclasts in the fracture areas. Collectively, polaprezinc promotes the fracture healing process efficiently by enhancing the activity of both osteoblasts and osteoclasts. Therefore, we suggest that drug repositioning of polaprezinc would be helpful for patients with fractures.

The complete chloroplast genome sequence of Adenophora kayasanensis Kitam. (Campanulaceae), an endemic to Korea.

Adenophora kayasanensis Kitam., belonging to the family Campanulaceae, is an important species because it is used as a type of herbal medicine and is endemic to Korea. Here, we report the complete chloroplast genome sequence of A. kayasanensis as determine by means of Illumina high-throughput sequencing. The complete cp genome was 169,433 bp in length, containing a large single copy (LSC) of 123,110 bp and a small single copy (SSC) of 8619 bp, which were separated by a pair of 29,085 bp inverted repeats (IRs). A total of 112 unique genes were annotated, consisting of 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. The overall GC content is 37.7%. A maximum-likelihood (ML) tree based on 76 protein-coding genes indicated that A. kayasanensis is closely related to Adenophora racemosa. This newly sequenced chloroplast genome will be useful to those engaged in research on the phylogenetic position of A. kayasanensis and the evolution of the genus Adenophora.

Targeted Transforaminal Epidural Blood Patch for Postdural Puncture Headache in Patients with Postlaminectomy Syndrome.

Postdural puncture headache is a leak of cerebrospinal fluid that lowers intracranial pressure and usually presents as a positional headache. If conservative treatments are not successful, the epidural blood patch is the gold standard of the treatment for dural puncture. The interlaminar approach is the most commonly used technique for an epidural blood patch. This case report describes a patient who was treated with a transforaminal epidural blood patch for postdural puncture headache following an acupuncture procedure on his lower back after two epidural blood patches using an interlaminar approach had failed. The patient underwent an acupuncture therapy for management of chronic low back pain due to postlaminectomy syndrome. After the procedure, the patient had a severe headache and the conservative treatment was not effective. The two interlaminar epidural blood patches at the L2-3 level and at the L3-4 level were failed. We performed transforaminal epidural blood patch at the L3-4 and L4-5 levels on the left side, the site of leakage in the MRI myelogram. His symptoms finally subsided without complication. This case demonstrates that targeted transforaminal epidural blood patch is a therapeutic option for the treatment of postdural puncture headache when epidural blood patch using an interlaminar approach is ineffective.

A novel antimicrobial peptide acting via formyl peptide receptor 2 shows therapeutic effects against rheumatoid arthritis.

In oriental medicine, centipede Scolopendra subspinipes mutilans has long been used as a remedy for rheumatoid arthritis (RA), a well-known chronic autoimmune disorder. However, the molecular identities of its bioactive components have not yet been extensively investigated. We sought to identify bioactive molecules that control RA with a centipede. A novel antimicrobial peptide (AMP) (scolopendrasin IX) was identified from Scolopendra subspinipes mutilans. Scolopendrasin IX markedly activated mouse neutrophils, by enhancing cytosolic calcium increase, chemotactic cellular migration, and generation of superoxide anion in neutrophils. As a target receptor for scolopendrasin IX, formyl peptide receptor (FPR)2 mediates neutrophil activation induced by the AMP. Furthermore, scolopendrasin IX administration strongly blocked the clinical phenotype of RA in an autoantibody-injected model. Mechanistically, the novel AMP inhibited inflammatory cytokine synthesis from the joints and neutrophil recruitment into the joint area. Collectively, we suggest that scolopendrasin IX is a novel potential therapeutic agent for the control of RA via FPR2.

Promotion of formyl peptide receptor 1-mediated neutrophil chemotactic migration by antimicrobial peptides isolated from the centipede Scolopendra subspinipes mutilans.

We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector-expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken together, our results suggest that the two AMPs stimulate neutrophils, leading to chemotactic migration through FPR1, and the two AMPs will be useful for the study of FPR1 signaling and neutrophil activation. [BMB Reports 2016; 49(9): 520-525].

A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1ß (IL-1ß) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm.