Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles.

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. RESULTS: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. CONCLUSIONS: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

HapEdit: an accuracy assessment viewer for haplotype assembly using massively parallel DNA-sequencing technologies.

The massively parallel sequencing technologies have recently flourished and dramatically cut the cost to sequence personal human genomes. Haplotype assembly from personal genomes sequenced using the massively parallel sequencing technologies is becoming a cost-effective and promising tool for human disease study. Computational assembly of haplotypes has been proved to be very accurate, but obviously contains errors. Here we present a tool, HapEdit, to assess the accuracy of assembled haplotypes and edit them manually. Using this tool, a user can break erroneous haplotype segments into smaller segments, or concatenate haplotype segments if the concatenated haplotype segments are sufficiently supported. A user can also edit bases with low-quality scores. HapEdit displays haplotype assemblies so that a user can easily navigate and pinpoint a region of interest. As inputs, HapEdit currently takes reads from the Polonator, Illumina, SOLiD, 454 and Sanger sequencing technologies.

Derivation of Corrosion Depth Formula According to Corrosion Factors in District Heating Water through Regression Analysis.

In order to predict the corrosion depth of a district heating pipeline, it is necessary to analyze various corrosion factors. In this study, the relationship between corrosion factors such as pH, dissolved oxygen, and operating time and corrosion depth was investigated using the Box-Behnken method within the response surface methodology. To accelerate the corrosion process, galvanostatic tests were conducted in synthetic district heating water. Subsequently, a multiple regression analysis was performed using the measured corrosion depth to derive a formula for predicting the corrosion depth as a function of the corrosion factors. As a result, the following regression formula was derived for predicting the corrosion depth: "corrosion depth (µm) = -133 + 17.1 pH + 0.00072 DO + 125.2 Time - 7.95 pH × Time + 0.002921 DO × Time".

Histologic evaluation of a catheter coated with paclitaxel PLGA nanoparticles in the internal jugular veins of rats.

The aim of this study is to investigate the potential impact of catheterization on intimal hyperplasia and explore the efficacy of Paclitaxel loaded PLGA nanoparticles (PTX-NPs) in preventing stenosis at the site of venous injury. Under general anesthesia, Central Venous Catheters were inserted into the rat's right internal jugular veins (IJV) using the cut-down technique. Twenty bare catheters (C) and twenty PTX-NPs coated catheters (P) were assigned to one of four groups (C2, C4, P2, or P4) based on catheter type and expected survival time. 2 or 4 weeks after surgery, IJVs were completely harvested by formalin fixation and gelatin infusion and slides were stained with H&E (Haematoxylin and Eosin) and Masson's technique. The P2 (Paclitaxel coating, 2 weeks) group showed the most proliferation among the four groups and the P4 (Paclitaxel coating, 4 weeks) showed a tendency to decrease proliferation. Additionally, the lumen size in the P4 group was about 6% smaller than in the P2 group, and there was a lower prevalence of stenotic grade in the P4 group. Our study suggests that PTX-NPs coated catheters may be effective in preventing venous stenosis if the intended usage is prolonged, rather than for a short-term period. Graphical abstract: Schematic representation of catheter functionalization and coating of PTX-NPs on Catheter. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00282-y.

Clinical Trials for Oral, Inhaled and Intravenous Drug Delivery System for Lung Cancer and Emerging Nanomedicine-Based Approaches.

Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.

A multicenter prospective study in type IV bone of a single type of implant.

PURPOSE: To analyze the success and survival rates of the Osstem GSII (Osstem, Busan, Korea) implant in type IV bone. MATERIALS: A prospective, multicenter (5 centers) study was conducted by examining the relationship between implant success and survival rates, and several patient and surgical parameters. The implants were placed in 82 patients who visited several nationwide dental hospitals and clinics between 2007 and 2008, followed by clinical and radiographic analyses. RESULTS: In type IV bone, the implant success and survival rates were 93.23% and 95.83%, respectively. The maxillary premolar and mandibular anterior tooth areas showed success rates of 100%. The most widely used implant diameter and length was 5.0 and 13 mm, respectively, but the diameter and length had no effect on success rates. However, success rates appeared to decrease with age. CONCLUSIONS: The results indicated that the Osstem GSII implant is highly effective in poor-quality type IV bone.

Localized Corrosion Occurrence in Low-Carbon Steel Pipe Caused by Microstructural Inhomogeneity.

In this study, the cause of failure of a low-carbon steel pipe meeting standard KS D 3562 (ASTM A135), in a district heating system was investigated. After 6 years of operation, the pipe failed prematurely due to pitting corrosion, which occurred both inside and outside of the pipe. Pitting corrosion occurred more prominently outside the pipe than inside, where water quality is controlled. The analysis indicated that the pipe failure occurred due to aluminum inclusions and the presence of a pearlite inhomogeneous phase fraction. Crevice corrosion occurred in the vicinity around the aluminum inclusions, causing localized corrosion. In the large pearlite fraction region, cementite in the pearlite acted as a cathode to promote dissolution of surrounding ferrite. Therefore, in the groundwater environment outside of the pipe, localized corrosion occurred due to crevice corrosion by aluminum inclusions, and localized corrosion was accelerated by the large fraction of pearlite around the aluminum inclusions, leading to pipe failure.

Protection of Hearing Loss in Ototoxic Mouse Model Through SPIONs and Dexamethasone-Loaded PLGA Nanoparticle Delivery by Magnetic Attraction.

Background: Ototoxicity currently has no available treatment other than medication withdrawal as soon as toxicity is suspected. The human inner ear organs have little potential for regeneration; thus, ototoxicity-induced hair cell injury is deemed permanent. Dexamethasone (Dexa) is a synthetic steroid analog that has significant potential for otoprotection in the treatment of various inner ear diseases; however, its low absorption into the inner ear prevents significant recovery of function. Nanoparticles facilitate targeted drug delivery, stabilize drug release, and increase half-life of the drug. Methods: This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded superparamagnetic iron oxide nanoparticles (SPIONs) and Dexa (PSD-NPs) to control localized drug delivery by magnetic attraction in the treatment of ototoxicity-induced hearing loss. PSD-NPs and without SPIONs (PD-NPs) were prepared using a nanoprecipitation method. Results: Using an inner ear simulating system, we confirmed that PSD-NPs has an otoprotective effect in organotypic culture that is enhanced by magnetic attraction. PSD-NPs delivered via intrabullar injection in a magnetic field penetrated the inner ear and prevented hearing loss progression to a greater degree than equivalent doses of Dexa or PSD-NPs alone (day 28: ototoxic: 80.0 ± 0.0 dB; Dexa 100: 60.0 ± 15.5 dB; PSD 100: 50.0 ± 8.2 dB; PSD 100 with magnet: 22.5 ± 5.0 dB; P < 0.05). The protective effects were confirmed in various in vivo and in vitro models of ototoxicity. Conclusion: Our findings suggest that SPIONs with Dexa and magnetic field application prevent the progression of ototoxicity-induced hearing loss through anti-apoptotic mechanisms in the inner ear.

Evaluation of the Influence of the Combination of pH, Chloride, and Sulfate on the Corrosion Behavior of Pipeline Steel in Soil Using Response Surface Methodology.

External damage to buried pipelines is mainly caused by corrosive components in soil solution. The reality that numerous agents are present in the corrosive environment simultaneously makes it troublesome to study. To solve that issue, this study aims to determine the influence of the combination of pH, chloride, and sulfate by using a statistical method according to the design of experiment (DOE). Response surface methodology (RSM) using the Box-Behnken design (BBD) was selected and applied to the design matrix for those three factors. The input corrosion current density was evaluated by electrochemical tests under variable conditions given in the design matrix. The output of this method is an equation that calculates the corrosion current density as a function of pH, chloride, and sulfate concentration. The level of influence of each factor on the corrosion current density was investigated and response surface plots, contour plots of each factor were created in this study.

Effect of Imidazole as Corrosion Inhibitor on Carbon Steel Weldment in District Heating Water.

Many research studies have been conducted on the corrosion inhibition performance of imidazole in acidic environments such as in the piping of a petrochemical plant. However, there has been no study on the effect of imidazole in alkaline conditions such as a local district water heating environment. Therefore, in this study, the effect of imidazole as a corrosion inhibitor on carbon steel weldment was investigated in alkaline district heating water. Inhibition efficiency and electrochemical properties were investigated by potentiodynamic polarization test and electrochemical impedance spectroscopy. As the concentration of imidazole increased up to 500 ppm, inhibition efficiency increased up to 91.7%. At 1000 ppm, inhibition efficiency decreased. Atomic force microscopy showed that surface coverage of imidazole at 1000 ppm is lower than that of imidazole at 500 ppm. X-ray photoelectron spectroscopy showed that with 500 ppm of imidazole, the amount of pyrrole type interaction is 4.8 times larger than pyridine type interaction. At 1000 ppm of imidazole, the amount of pyridine type interaction is 3.49 times larger than pyrrole type interaction. Depending on the concentration of imidazole, the ratio of interaction between carbon steel and imidazole affected inhibition efficiency.

Calibrating the Impressed Anodic Current Density for Accelerated Galvanostatic Testing to Simulate the Long-Term Corrosion Behavior of Buried Pipeline.

Various studies have been conducted to better understand the long-term corrosion mechanism for steels in a soil environment. Here, electrochemical acceleration methods present the most efficient way to simulate long-term corrosion. Among the various methods, galvanostatic testing allows for accelerating the surface corrosion reactions through controlling the impressed anodic current density. However, a large deviation from the equilibrium state can induce different corrosion mechanisms to those in actual service. Therefore, applying a suitable anodic current density is important for shortening the test times and maintaining the stable dissolution of steel. In this paper, to calibrate the anodic current density, galvanostatic tests were performed at four different levels of anodic current density and time to accelerate a one-year corrosion reaction of pipeline steel. To validate the appropriate anodic current density, analysis of the potential vs. time curves, thermodynamic analysis, and analysis of the specimen's cross-sections and products were conducted using a validation algorithm. The results indicated that 0.96 mA/cm2 was the optimal impressed anodic current density in terms of a suitable polarized potential, uniform corrosion, and a valid corrosion product among the evaluated conditions.

Biodistribution of poly clustered superparamagnetic iron oxide nanoparticle labeled mesenchymal stem cells in aminoglycoside induced ototoxic mouse model.

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC's were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery. The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC's to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy.

HAPLOWSER: a whole-genome haplotype browser for personal genome and metagenome.

SUMMARY: Haplotype assembly is becoming a very important tool in genome sequencing of human and other organisms. Although haplotypes were previously inferred from genome assemblies, there has never been a comparative haplotype browser that depicts a global picture of whole-genome alignments among haplotypes of different organisms. We introduce a whole-genome HAPLotype brOWSER (HAPLOWSER), providing evolutionary perspectives from multiple aligned haplotypes and functional annotations. Haplowser enables the comparison of haplotypes from metagenomes, and associates conserved regions or the bases at the conserved regions with functional annotations and custom tracks. The associations are quantified for further analysis and presented as pie charts. Functional annotations and custom tracks that are projected onto haplotypes are saved as multiple files in FASTA format. Haplowser provides a user-friendly interface, and can display alignments of haplotypes with functional annotations at any resolution. AVAILABILITY: Haplowser, written in Java, supports multiple platforms including Windows and Linux. Haplowser is publicly available at http://embio.yonsei.ac.kr/haplowser .

Effects of Corrosion on Mechanical Properties of Welded Carbon Steel Pipe in District Heating Water.

This study examined the effect of corrosion on mechanical properties of welded carbon steel pipe in district heating water. To evaluate the corrosion properties, potentiodynamic tests were conducted and a galvanostatic test was used to accelerate corrosion. Tensile tests and microstructure observations were performed to figure out the degradation of the corroded region, and stress intensity factors were calculated. As a result of the potentiodynamic tests, welded carbon steel pipe showed uniform corrosion and the total charge was calculated. Using the galvanostatic test, the current density at the equivalent aging time was applied to the specimens. The tensile tests showed that according to corrosion damages, mechanical properties were degraded due to corrosion. Through the microstructure observations and calculations of stress intensity factors, the corrosion of the welded carbon steel pipe induced the degradation of mechanical properties. The mode of fracture was changed from ductile to brittle fracture with increasing aging time.

A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs.

Mesenchymal Stem Cell Lines Isolated by Different Isolation Methods Show Variations in the Regulation of Graft-versus-host Disease.

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft-versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and IFN-γ production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.

Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.

OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged salivary gland (SG) tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs) can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 × 10(6)) were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs) and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs) was observed in vitro using a co-culture system. RESULTS: The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18%) were observed to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

Nationwide cancer incidence in Korea, 2003-2005.

PURPOSE: To estimate the current cancer burden in Korea, newly diagnosed cancer cases and cancer incidence rates were calculated for the years 2003~2005. MATERIALS AND METHODS: The cancer incidence cases and rates were calculated from the Korea National Cancer Incidence Database. Crude and age-standardized incidence rates were calculated by gender for specified cancer sites in 5-year age groups. RESULTS: From 2003 to 2005, 398,824 cases of cancer were newly diagnosed in Korea (218,856 in men and 179,968 in women). For all sites combined, the crude incidence rate (CR) was 300.0 and 248.2 for men and women and the age-standardized incidence rate (ASR) was 297.0 and 191.2 per 100,000, respectively. Among men, five leading cancers were stomach (CR 66.0, ASR 64.2), lung (CR 48.5, ASR 50.3), liver (CR 44.9, ASR 42.1), colon and rectum (CR 37.9, ASR 37.2), and prostate cancer (CR 12.7, ASR 13.8). Among women, five leading cancers were breast (CR 37.3, ASR 29.0), thyroid (CR 36.2, ASR 28.8), stomach (CR 34.1, ASR 25.4), colon and rectum (CR 28.0, ASR 21.1), and lung cancer (CR 17.9, ASR 12.8). In the 0~14-year-old group, leukemia was the most common in both sexes; in the 15~34 group, the most common cancer was stomach cancer for men and thyroid cancer for women; in the 35~64 group, stomach cancer for men and breast cancer for women; among those 65 and over, lung cancer for men and stomach cancer, for women, respectively. CONCLUSION: The cancer incidence rates have increased in recent years, and more cancers are expected to develop as Korea is quickly becoming an aged society. The cancer incidence statistics in this report can be used as an important source to effectively plan and evaluate the cancer control program in Korea.