Identification of a bioactive core sequence from human laminin and its applicability to tissue engineering

Finding bioactive short peptides derived from proteins is a critical step to the advancement of tissue engineering and regenerative medicine, because the former maintains the functions of the latter without immunogenicity in biological systems. Here, we discovered a bioactive core nonapeptide sequence, PPFEGCIWN (residues 2678e2686; Ln2-LG3-P2-DN3), from the human laminin a2 chain, and investigated the role of this peptide in binding to transmembrane proteins to promote intracellular events leading to cell functions. This minimum bioactive sequence had neither secondary nor tertiary structures in a computational structure prediction. Nonetheless, Ln2-LG3-P2-DN3 bound to various cell types as actively as laminin in cell adhesion assays. The in vivo healing tests using rats revealed that Ln2-LG3-P2-DN3 promoted bone formation without any recognizable antigenic activity. Ln2-LG3-P2-DN3-treated titanium (Ti) discs and Ti implant surfaces caused the enhancement of bone cell functions in vitro and induced faster osseointegration in vivo, respectively. These findings established a minimum bioactive sequence within human laminin, and its potential application value for regenerative medicine, especially for bone tissue engineering.OAIID:oai:osos.snu.ac.kr:snu2015-01/102/2008003883/7ADJUST_YN:YEMP_ID:A078517DEPT_CD:861CITE_RATE:8.557FILENAME:044-biomaterials 201512 73() 96-109.pdfDEPT_NM:치의학과SCOPUS_YN:YCONFIRM:

Prognostic value of low muscle mass at the 12th thoracic vertebral level in multiple myeloma treated with transplantation: CAREMM-2101 study

PURPOSEAutologous hematopoietic stem cell transplantation (ASCT) has been introduced as a standard treatment for newly diagnosed multiple myeloma (NDMM) following novel agent-based induction chemotherapy. This study investigated whether pre-ASCT low muscle mass evaluated using the paraspinal muscle index (PMI) at the 12th thoracic vertebra (T12) level is a reliable prognostic marker in NDMM after chemotherapy.METHODSA multi-center registry database was retrospectively analyzed. Between 2009 and 2020, 190 patients with chest computed tomography images underwent frontline ASCT following induction therapy. The PMI was defined as the value of the paraspinal muscle area at the T12 level divided by the square of the patient’s height. The cut-off value indicating a low muscle mass was sex-specific, using the lowest quintiles.RESULTSOf the 190 patients, 38 (20%) were in the low muscle mass group. The low muscle mass group had a lower 4-year overall survival (OS) rate than the non-low muscle mass group (68.5% vs. 81.2%; P = 0.074). The median progression-free survival (PFS) in the low muscle mass group was significantly shorter compared with the non-low muscle mass group (23.3 months vs. 29.2 months; P = 0.029). The cumulative incidence of transplant-related mortality (TRM) was significantly higher in the low muscle mass group than in the non-low muscle mass group (4-year probability of TRM incidence, 10.6% vs. 0.7%; P < 0.001). In contrast, no significant difference in the cumulative incidence of disease progression was found between the two groups. Multivariate analysis revealed that low muscle mass was associated with significant negative outcomes for OS [(hazard ratio (HR): 2.14; P = 0.047], PFS (HR: 1.78; P = 0.012), and TRM (HR: 12.05; P = 0.025).CONCLUSIONParaspinal muscle mass may have a prognostic role in NDMM patients who undergo ASCT. Patients with low paraspinal muscle mass have lower survival outcomes compared to non-low muscle mass group

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 in Multilevel Posterolateral Lumbar Fusion in a Prospective, Randomized, Controlled Trial

Objective This study is an investigator-initiated, prospective, randomized, controlled study to evaluate the efficacy and safety of the combined use of recombinant human BMP-2 (rhBMP-2) and a hydroxyapatite (HA) carrier in multilevel fusion in patients with adult spinal deformity (ASD). Methods Thirty patients underwent posterolateral fusion for lumbar spinal deformities at 3 to 5 segments between L1 and S1. The patients received rhBMP-2+HA or HA on the left or right side of the transverse processes. They were followed up regularly at 1, 3, 6, and 12 months postoperatively. Fusion was defined according to the bone bridging on computed tomography scans. The fusion rate per segment was subanalyzed. Function and quality of life as well as pain in the lower back and lower extremities were evaluated. Results The union rate for the rhBMP-2+HA group was 100% at 6 and 12 months. The union rate for the HA group was 77.8% (21 of 27) at 6 months and 88.0% (22 of 25) at 12 months (p = 0.014 at 6 months; not significant at 12 months). All segments were fused at 6 and 12 months in the rhBMP-2+HA group (p < 0.001). In the HA group, 108 of 115 segments (93.5%) were fused at 6 months and 105 of 109 segments (96.3%) at 12 months. Other clinical parameters (visual analogue scale, 36-item Short Form Health Survey, and Scoliosis Research Society-22 scores) improved compared to baseline. Conclusion Combining rhBMP-2 and an HA carrier is a safe and effective method to achieve multilevel fusion in patients with ASD

The effect of the DLTIDDSYWYRI motif of the human laminin α2 chain on implant osseointegration

Considerable effort has been directed towards replacing lost teeth using tissue-engineering methods such as titanium implants. A number of studies have tried to modify bioinert titanium surfaces by coating them with functionally bioactive molecules for faster and stronger osseointegration than pure titanium surfaces. Recently, peptides have been recognized as valuable scientific tools in the field of tissue-engineering. The DLTIDDSYWYRI motif of the human laminin-2 α2 chain has been previously reported to promote the attachment of various cell types; however, the in vivo effects of the DLTIDDSYWYRI motif on new bone formation have not yet been studied. To examine whether a laminin-2-derived peptide can promote osseointegration by accelerating new bone formation in vivo, we applied titanium implants coated with the DLTIDDSYWYRI motif in a rabbit tibia model. The application of the DLTIDDSYWYRI motif-treated implant to tibia wounds enhanced collagen deposition and alkaline phosphatase expression. It significantly promoted implant osseointegration compared with treatment with scrambled peptide-treated implants by increasing the bone-to-implant contact ratio and bone area. These findings support the hypothesis that the DLTIDDSYWYRI motif acts as an effective osseointegration accelerator by enhancing new bone formation.Considerable effort has been directed towards replacing lost teeth using tissue-engineering methods such as titanium implants. A number of studies have tried to modify bioinert titanium surfaces by coating them with functionally bioactive molecules for faster and stronger osseointegration than pure titanium surfaces. Recently, peptides have been recognized as valuable scientific tools in the field of tissue-engineering. The DLTIDDSYWYRI motif of the human laminin-2 α2 chain has been previously reported to promote the attachment of various cell types; however, the in vivo effects of the DLTIDDSYWYRI motif on new bone formation have not yet been studied. To examine whether a laminin-2-derived peptide can promote osseointegration by accelerating new bone formation in vivo, we applied titanium implants coated with the DLTIDDSYWYRI motif in a rabbit tibia model. The application of the DLTIDDSYWYRI motif-treated implant to tibia wounds enhanced collagen deposition and alkaline phosphatase expression. It significantly promoted implant osseointegration compared with treatment with scrambled peptide-treated implants by increasing the bone-to-implant contact ratio and bone area. These findings support the hypothesis that the DLTIDDSYWYRI motif acts as an effective osseointegration accelerator by enhancing new bone formation.Tissue-engineeringThis work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by MEST (Grant No. 2011-0007662) and the Mid-career Researcher Program through NRF, funded by MEST (Grant No. 2010-0014662).OAIID:oai:osos.snu.ac.kr:snu2013-01/102/2008003883/1SEQ:1PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:2008003883ADJUST_YN:NEMP_ID:A078517DEPT_CD:861CITE_RATE:7.404FILENAME:Biomaterials 201305 34(16) 4027-37.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YCONFIRM:

Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney

Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury

Pneumopericardium as a Complication of Pericardiocentesis

Pneumopericardium is a rare complication of pericardiocentesis, occurring either as a result of direct pleuro-pericardial communication or a leaky drainage system. Air-fluid level surrounding the heart shadow within the pericardium on a chest X-ray is an early observation at diagnosis. This clinical measurement and process is variable, depending on the hemodynamic status of the patient. The development of a cardiac tamponade is a serious complication, necessitating prompt recognition and treatment. We recently observed a case of pneumopericardium after a therapeutic pericardiocentesis in a 20-year-old man with tuberculous pericardial effusion

The Possible Role of Nitric Oxide on Enteric Nerves-Mediated Relaxation of the Gastric Smooth Muscle of the Guinea Pig

The influence of the enteric nerves stimulation on the contractility of gastric circular muscle was studied in guinea pig stomachs. The enteric nerves were activated by electric field stimulation(EFS; 90 V, 1 rns, 32 Hz square pulses for 1 s), EFS produced initial transient contraction followed by relaxation and slow recovery. The initial contraction was sensitively blocked by treatment with atropine. The following relaxation still occurred in nonadrenergic noncholinergidNANC) state. EFSinduced relaxation was reduced by LG-nitro-L-arginine(L-NNA), a nitric oxide(NO) synthase inhibitor. The relaxation was restored from the suppressed state after the application of L-arginine(L-arg), a substrate of nitric oxide synthase. With conventional intracellular recording, slow wave and inhibitory junction potential(IJP) were recorded. L-NNA had no effect on IJP, while apamin blocked it. In conclusion, it is suggested that NO may playa major role in EFS-induced relaxation. The exact mechanism of this relaxation is unknown, but the relaxation does not result from the IJP induced by the activation of apamin-sensitive potassium channels