Stretchable Functional Nanocomposites for Soft Implantable Bioelectronics.

Material advances in soft bioelectronics, particularly those based on stretchable nanocomposites─functional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bonds─have driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.

INF2 mutations in patients with a broad phenotypic spectrum of Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis.

Mutations in INF2 are associated with the complex symptoms of Charcot-Marie-Tooth disease (CMT) and focal segmental glomerulosclerosis (FSGS). To date, more than 100 and 30 genes have been reported to cause these disorders, respectively. This study aimed to identify INF2 mutations in Korean patients with CMT. This study was conducted with 743 Korean families with CMT who were negative for PMP22 duplication. In addition, a family with FSGS was included in this study. INF2 mutations were screened using whole exome sequencing (WES) and filtering processes. As the results, four pathogenic INF2 mutations were identified in families with different clinical phenotypes: p.L78P and p.L132P in families with symptoms of both CMT and FSGS; p.C104Y in a family with CMT; and p.R218Q in a family with FSGS. Moreover, different CMT types were observed in families with CMT symptoms: CMT1 in two families and Int-CMT in another family. Hearing loss was observed in two families with CMT1. Pathogenicity was predicted by in silico analyses, and considerable conformational changes were predicted in the mutant proteins. Two mutations (p.L78P and p.C104Y) were unreported, and three families showed de novo mutations that were putatively occurred from fathers. This study suggests that patients with INF2 mutations show a broad phenotypic spectrum: CMT1, CMT1 + FSGS, CMTDIE + FSGS, and FSGS. Therefore, the genotype-phenotype correlation may be more complex than previously recognized. We believe that this study expands the clinical spectrum of patients with INF2 mutations and will be helpful in the molecular diagnosis of CMT and FSGS.

Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease.

INTRODUCTION: Demyelinating Charcot-Marie-Tooth disease (CMT) is caused by mutations in the genes that encode myelinating proteins or their transcription factors. Our study thus sought to assess the therapeutic effects of cytokines secreted from mesenchymal stem cells (MSCs) on this disease. METHODS: The therapeutic potential of Wharton's jelly MSCs (WJ-MSCs) and cytokines secreted by WJ-MSCs was evaluated on Schwann cells (SCs) exhibiting demyelination features, as well as a mouse model of demyelinating CMT. RESULTS: Co-culture with WJ-MSC protected PMP22-overexpressing SCs from apoptotic cell death. Using a cytokine array, the secretion of growth differentiation factor-15 (GDF-15) and amphiregulin (AREG) was found to be elevated in WJ-MSCs when co-incubated with the PMP22-overexpressing SCs. Administration of both cytokines into trembler-J (Tr-J) mice, an animal model of CMT, significantly enhanced motor nerve conduction velocity compared to the control group. More importantly, this treatment alleviated the demyelinating phenotype of Tr-J mice, as demonstrated by an improvement in the mean diameter and g-ratio of the myelinated axons. CONCLUSIONS: Our findings demonstrated that WJ-MSCs alleviate the demyelinating phenotype of CMT via the secretion of several cytokines. Further elucidation of the underlying mechanisms of GDF-15 and AREG in myelination might provide a robust basis for the development of effective therapies against demyelinating CMT.

Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F.

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

Predictors of difficult intubation when using a videolaryngoscope with an intermediate-angled blade during the first attempt: a prospective observational study.

The curvature of a videolaryngoscope blade has been diversified from the standard macintosh-type to the hyperacute-angle-type, resulting in different performances. We aimed to determine the intubation success rate and identify predictors of difficult intubation when using an intermediate-angled videolaryngoscope in the first attempt of intubation under routine anaesthesia settings. We enrolled 808 patients between 19 and 79 years of age, scheduled for elective surgeries under general anaesthesia with orotracheal intubation from July 2017 to November 2018; patients who were candidates for awake intubation were excluded. We obtained patient demographic data and performed airway evaluation before induction of anaesthesia for elective surgeries. We used the UEScope for tracheal intubation with a hockey stick-shaped malleable stylet. The intubation time was defined as the total duration from the entry of the blade into the oropharynx to the detection of first end-tidal carbon dioxide capnogram; this duration was recorded along with the number of intubation attempts. Difficult intubation was defined as either > 60 s duration for tracheal intubation, or > 1 intubation attempt. The use of the UEScope demonstrated a 99.4% success rate for intubation; however, increased difficulties were observed in patients who were male, obese, had a short thyromental distance, limited mouth opening, and high upper-lip-bite test class. Despite the high intubation success rate using an intermediate-angled videolaryngoscope, we recommend preparing backup plans, considering the increased difficulty in patients with certain preoperative features.Clinical trial number and registry URL: Clinical Trials.gov Identifier: NCT03215823 (Date of registration: 12 July).

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol's effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.

Comparison of Lip Line Cant Change After 1-Jaw and 2-Jaw Surgery.

OBJECTIVES: The purpose of this study was to compare the lip line cant (LLC) changes after 1 and 2-jaw surgery, and to evaluate the correlations of the craniofacial factors affecting LLC. METHODS: The study subjects were selected (LLC amount within 1.5-6.0°) from among the patients diagnosed with Class III malocclusion who underwent one (n = 20) or 2-jaw surgery (n = 20). Cone beam computed tomography images were obtained immediately before the operation (T1) and 6 months after the operation (T2). Preoperative and postoperative craniofacial measurements were obtained. RESULTS: The study subjects showed 3.12° LLC on average before undergoing 1-jaw surgery, and their LLC changed to 1.27° after the surgery. As for 2-jaw surgery, the subjects showed 3.38° LLC on average before the surgery and 0.98° after the surgery. LLC at pre-treatment may be more affected by a cant of the occlusal plane in the mandible than maxilla. In the comparison of the value of changes of LLC, the value of 2-jaw surgery was bigger than the value of 1-jaw surgery but the difference was statistically insignificant. LIMITATIONS: This study had a limitation in that the muscles were not considered. And the metal bracket or metal crown and bridge, however, can cause noise and blurring artifacts in CT, which can lead to a low resolution. And the limited number of the patients should be considered. CONCLUSIONS: In correlation analysis, both pre-surgery LLC and change of LLC have correlation with almost all the craniofacial measurement. Lip-line cant of patients with facial asymmetry has higher correlation with mandibular cant than with other cants. To improve the LLC, a surgical plan should be established to minimize the mandibular cant using the computer simulation as well as the maxillary cant.

Intentional cyanoacrylate ingestion: A rare cause of delayed gastric perforation requiring gastric wedge resection.

Cyanoacrylate (LOCTITE® 401™) is a fast-acting adhesive available nationwide, with medical and household uses. Most cases of cyanoacrylate exposure are accidental and occur in children less than 5years old. Various routes of exposure have been reported including the dermal, oral, ocular, otic, nasal, and urethral routes; however, very few result in serious complication and mortality. Although a few cases of airway obstruction related to cyanoacrylate ingestion have been reported, intentional cyanoacrylate ingestion-induced gastrointestinal tract injury has scarcely been reported. In addition, there have been no reports of serious complications following intentional cyanoacrylate ingestion requiring surgical intervention. Herein, we report a case of intentional ingestion of cyanoacrylate in a 70-year-old man who required gastric wedge resection due to delayed gastric perforation.

Epidemiology and virologic investigation of human enterovirus 71 infection in the Republic of Korea from 2007 to 2012: a nationwide cross-sectional study.

BACKGROUND: Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea. METHODS: We analyzed characteristics of the EV71 infection-associated epidemic from collected specimens and clinical information from 9987 patients with suspected EV infection from the National EV Surveillance System in ROK. To identify the EV71 subgenotype, the homology of viral protein 1 sequences obtained using reverse transcription polymerase chain reaction was compared with the sequences on other countries available from GenBank database. RESULTS: EV71 was detected in 585 (16.7 %) specimens (cerebrospinal fluid, stool or rectal swabs, throat swabs and blood) during study period and was most frequently observed during epidemic seasons in 2009-2012. Major manifestations due to EV71 infection were HFMD (62.2 %) and HFMD with severe neurological complications (28.4 %). Five deaths (0.9 %) due to EV71 infection occurred, with an increased mortality rate during the period after 2009. Most patients (476; 81.4 %) were less than 5 years of age. Analysis of the monthly distribution showed that there was an obvious seasonal pattern to the epidemics, with infections appearing from June to August. The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam. CONCLUSIONS: This surveillance provided valuable data on the epidemic characteristics of EV71 infections in ROK during a 6-year period. Our findings provide data to assist during future outbreaks of EV71 and associated acute neurologic disease.

Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families.

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the FGD4 gene. Most CMT4H patients are in consanguineous Mediterranean families characterized by early onset and slow progression. We identified two CMT4H patients from a Korean CMT cohort, and performed a detailed genetic and clinical analysis in both cases. Both patients from nonconsanguineous families showed characteristic clinical manifestations of CMT4H including early onset, scoliosis, areflexia, and slow disease progression. Exome sequencing revealed novel compound heterozygous mutations in FGD4 as the underlying cause in both families (p.Arg468Gln and c.1512-2A>C in FC73, p.Met345Thr and c.2043+1G>A (p.Trp663Trpfs*30) in FC646). The missense mutations were located in highly conserved RhoGEF and PH domains which were predicted to be pathogenic in nature by in silico modeling. The CMT4H occurrence frequency was calculated to 0.7% in the Korean demyelinating CMT patients. This study is the first report of CMT4H in Korea. FGD4 assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.

Treatment effects of a modified palatal anchorage plate for distalization evaluated with cone-beam computed tomography.

INTRODUCTION: The purpose of this study was to evaluate the treatment effects of maxillary posterior tooth distalization performed by a modified palatal anchorage plate appliance with cephalograms derived from cone-beam computed tomography. METHODS: The sample consisted of 40 lateral cephalograms obtained from the cone-beam computed tomography images of 20 Class II patients (7 men, 13 women; average age, 22.9 years) who underwent bilateral distalization of their maxillary dentition. The lateral cephalograms were derived from the cone-beam computed tomography images taken immediately before placement of a modified palatal anchorage plate appliance and at the end of distalization. Paired t tests were used for comparisons of the changes. RESULTS: The distal movement of the maxillary first molar was 3.3 ± 1.8 mm, with distal tipping of 3.4° ± 5.8° and intrusion of 1.8 ± 1.4 mm. Moreover, the maxillary incisors moved 3.0 ± 2.7 mm lingually, with lingual tipping of 6.2° ± 7.6° and insignificant extrusion (1.1 mm; P = 0.06). The occlusal plane angle was increased significantly (P = 0.0001). CONCLUSIONS: The maxillary first molar was distalized by 3.3 mm at the crown and 2.2 mm at root levels, with distal tipping of 3.4°. It is recommended that clinicians should consider using the modified palatal anchorage plate appliance in treatment planning for patients who require maxillary total arch distalization.

Optimizing tenderness of M. Semitendinosus steak for elderly people with the combination of ficin and sous-vide cooking.

This study aimed to evaluate the sous-vide cooking and ficin treatment effects on the tenderness of beef steak and optimize it for the elderly using response surface methodology (RSM). The M. semitendinosus (ST) from Chikso cattle was shaped into 5 × 5 × 2.54 cm pieces. Ficin solution was injected into the ST steak at 10% of the meat weight, and sous-vide cooked in a water bath at 65 °C for 6 or 12 h. As ficin concentration increased, L*- and a*-value, shear force, and hardness decreased, while soluble peptides increased (P < 0.05). As cooking time increased, cooking loss and collagen solubility of the steak increased (P < 0.05). An interaction effect between ficin and sous-vide cooking was found in L*- and a*-value, shear force, hardness, and soluble peptides (P < 0.05). A model to optimize the hardness for elderly people was established (R2 = 0.7991). Optimization conditions by RSM were 0.86 U/L with 8.87 h (23 N/cm3) for tooth intake (grade 1), 16.31 U/L with 13.24 h (3 N/cm3) for gums intake (grade 2), according to KS H 4897 and Universal Design Foods concept for the elderly. These optimized conditions enable the production of customized products tailored to the oral conditions of elderly people.

Tissue-specific gelatin bioink as a rheology modifier for high printability and adjustable tissue properties.

Decellularized extracellular matrix (dECM) has emerged as an exceptional biomaterial that effectively recapitulates the native tissue microenvironment for enhanced regenerative potential. Although various dECM bioinks derived from different tissues have shown promising results, challenges persist in achieving high-resolution printing of flexible tissue constructs because of the inherent limitations of dECM's weak mechanical properties and poor printability. Attempts to enhance mechanical rigidity through chemical modifications, photoinitiators, and nanomaterial reinforcement have often compromised the bioactivity of dECM and mismatched the desired mechanical properties of target tissues. In response, this study proposes a novel method involving a tissue-specific rheological modifier, gelatinized dECM. This modifier autonomously enhances bioink modulus pre-printing, ensuring immediate and precise shape formation upon extrusion. The hybrid bioink with GeldECM undergoes a triple crosslinking system-physical entanglement for pre-printing, visible light photocrosslinking during printing for increased efficiency, and thermal crosslinking post-printing during tissue culture. A meticulous gelatinization process preserves the dECM protein components, and optimal hybrid ratios modify the mechanical properties, tailoring them to specific tissues. The application of this sequential multiple crosslinking designs successfully yielded soft yet resilient tissue constructs capable of withstanding vigorous agitation with high shape fidelity. This innovative method, founded on mechanical modulation by GeldECM, holds promise for the fabrication of flexible tissues with high resilience.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication.

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

Nano-chemical priming strategy to enhance TGF-ß resistance and anti-tumor activity of natural killer cells.

Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-ß), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-ß-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-ß receptor activity, thereby blocking TGF-ß signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-ß, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-ß on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.

Self-Powered Electrical Bandage Based on Body-Coupled Energy Harvesting.

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu3Ti4O12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology.

Fusogenic liposomes encapsulating mitochondria as a promising delivery system for osteoarthritis therapy.

Many attempts have been made to use mitochondria (MT) to treat human diseases; however, MT are large, making them difficult to deliver effectively. Therefore, a transfer strategy based on membrane fusion was established. Fusogenic mitochondrial capsules (FMCs) comprising a neutral lipid (PE), a cationic lipid (DOTAP), an aromatic lipid (Liss Rhod PE), and three types of liposome (FMC0, FMC1, and FMC2), were designed and synthesized. The amount of DOTAP, which affects membrane fusion efficiency, differed between FMC preparations. The characteristics of these FMCs were analyzed by DLS, TEM, and AFM, and the encapsulation and fusion efficiency between FMC-MT and FMC-chondrocytes were confirmed by FRET, mtDNA copy number, and CLSM, respectively. Compared with naked MT, delivery of FMCs to chondrocytes was faster and more efficient. Moreover, fusion was a more stable delivery method than endocytosis, as evidenced by reduced induction of mitophagy. In vitro and in vivo experiments revealed that FMCs reduced expression of inflammatory cytokines and MMP13, increased expression of extracellular matrix components, and promoted cartilage regeneration. These findings suggest that FMCs are a highly effective and promising strategy for delivery of MT to promote cartilage regeneration, and highlight their potential as a novel platform for MT transfer therapy.

Whole-genome sequencing in clinically diagnosed Charcot-Marie-Tooth disease undiagnosed by whole-exome sequencing.

Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot-Marie-Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot-Marie-Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing.

Enhancement of fluoride activity against Streptococcus mutans biofilms by a substance separated from Polygonum cuspidatum.

Polygonum cuspidatum is a plant with spreading rhizomes and numerous reddish-brown stems that has been used in Korean folk medicine to improve oral hygiene. Nevertheless, there are no reports related to its possible effect on the virulence of dental biofilms. In this study, the ability of a fraction (F1) separated from P. cuspidatum, alone or in combination with fluoride, to disrupt virulence factors and the composition of Streptococcus mutans biofilms was examined. F1 was mainly composed of resveratrol, emodin and physcion (approximately 16.2%, 18.9% and 2.07% of the weight of F1, respectively). F1 showed inhibitory effects on acid production and F-ATPase activity of S. mutans in biofilms, and could enhance fluoride activity against acid production and acid tolerance of S. mutans in biofilms. When S. mutans biofilms were briefly treated with F1 (10 min, a total of five times), the biomass accumulation, water-insoluble polysaccharides and intracellular iodophilic polysaccharides were reduced. Furthermore, the fluoride activity against biomass accumulation was enhanced by F1. These results suggest that F1 may be useful in the control of dental biofilms and in improving the cariostatic properties of fluoride without increasing its exposure.

Strategies for accelerating osteogenesis through nanoparticle-based DNA/mitochondrial damage repair.

The efficiency of gene therapy is often dictated by the gene delivery system. Cationic polymers are essential elements of gene delivery systems. The relatively cheap cationic polymer, polyethyleneimine, has high gene delivery efficiency and is often used for gene delivery. However, the efficiency of gene therapy with polyethyleneimine-pDNA polyplex (PEI) is low. Human mesenchymal stem cells transfected with polyethyleneimine and a plasmid carrying the important osteogenic differentiation gene runt-related transcription factor 2 (RUNX2) accumulated DNA double-strand breaks and mitochondrial damage proportional to the amount of polyethyleneimine, reducing viability. Genomic/cellular stabilizer mediating RUNX2 delivery (GuaRD), a new reagent incorporating RS-1 NPs developed in this study, promoted DNA repair and prevented the accumulation of cell damage, allowing the delivery of pRUNX2 into hMSCs. while maintaining genome and mitochondrial stability. DNA damage was significantly lower and the expression of DNA repair-related genes significantly higher with GuaRD than with PEI. In addition, GuaRD improved mitochondrial stability, decreased the level of reactive oxygen species, and increased mitochondrial membrane potential. Osteogenic extracellular matrix (ECM) expression and calcification were higher with GuaRD than with PEI, suggesting improved osteogenic differentiation. These results indicate that lowering the cytotoxicity of PEI and improving cell stability are key to overcoming the limitations of conventional gene therapy, and that GuaRD can help resolve these limitations.