Comparison of Antibacterial Activities of Korean Pine (Pinus densiflora) Needle Steam Distillation Extract on Escherichia coli and Staphylococcus aureus Focusing on Membrane Fluidity and Genes Involved in Membrane Lipids and Stress.

The antibacterial activity and mechanism of Pinus densiflora extracts against Escherichia coli and Staphylococcus aureus were investigated. The growth inhibition tests of paper diffusion and optical density exhibited that the extracts have potent antibacterial potentials against foodborne pathogens. The measurement of membrane fluidity by fluorescence polarization has indicated that one of the antibacterial mechanisms involves the disruption of membrane integrity resulting in an increase in the membrane fluidity in both of E. coli and S. aureus. The alteration of fatty acid composition was accompanied by the disturbance of membranes thus shifting the proportion of saturated verses unsaturated fatty acids or trans fatty acids from 1.27:1 to 1.35:1 in E. coli and 1.47:1 to 2.31:1 in S. aureus, most likely to compensate for the increased membrane fluidity by means of a higher proportion of saturated fatty acids which is known to render rigidity in membranes. Realtime q-PCR (polymerase chain reaction) analysis of fatty acid synthetic genes and bacterial stress genes revealed that there was minimal influence of P. densiflora extracts on fatty acid genes except for fab I and the stress rpos in E. coli, and relatively greater impact on fatty acid genes and the stress sigB in S. aureus.

The landscape of decentralized clinical trials (DCTs): focusing on the FDA and EMA guidance.

Decentralized clinical trials (DCTs) consist of off-site trial-related procedures referred to as decentralized elements. We aimed to provide an overview of the landscape of DCTs by comparing regulatory guidance reports and analyzing decentralized elements from clinical trial registries. Two guidance reports on DCTs published by the U.S. Food and Drug Administration and the European Medicines Agencies were summarized and analyzed. Both guidance publications commonly emphasized an assessment of the appropriateness of decentralized elements along 2 axes: patient safety and data integrity. DCT cases were identified from ClinicalTrials.gov by searching with 6 keywords: decentralized, remote, mobile, digital, virtual, and hybrid. Cases where the keyword was used in a non-DCT context, such as digital flexor tendon, were excluded by means of natural language processing. A total of 4,874 trials were identified as DCT cases, with annual increases, especially after 2020. The most common keywords were 'mobile' and 'digital' (36.2% and 24.8%, respectively). Interventions in the DCT cases were analyzed by means of a network analysis. Behavioral and technological tokens were frequently combined, such as 'rehabilitation' and 'app.' Drugs were used in only 1.8% of the DCT cases. Of these, most drugs had been approved previously (96.8%) and were in oral formulation (67.2%). Most of the DCT cases identified in this study involved simple interventions and low-risk drugs. These characteristics were in accordance with the common recommendations in the DCT guidance publications.

Safety, Tolerability, and Pharmacokinetics of a Novel Macrocyclic Gadolinium-Based Contrast Agent, HNP-2006, in Healthy Subjects.

OBJECTIVES: Gadolinium-based contrast agents (GBCAs) are indispensable in contrast-enhanced magnetic resonance imaging. A higher risk of gadolinium deposition in linear GBCAs required the introduction of macrocyclic GBCAs with a stable molecular structure. We conducted the first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (PKs) of HNP-2006, a novel macrocyclic GBCA, in healthy male subjects. MATERIALS AND METHODS: A randomized, placebo-controlled, double-blind, single-ascending dose study was conducted. Subjects received either a single intravenous bolus injection of HNP-2006 or its matching placebo with a treatment-to-placebo ratio of 6:2 at the dose level of 0.02, 0.05, 0.1, 0.2, and 0.3 mmol/kg. Safety was assessed through routine clinical assessments. Blood sampling and urine collection were performed up to 72 hours postdose for PK assessments. Noncompartmental methods were used to calculate PK parameters, and a population PK model was constructed. RESULTS: Overall, 40 subjects completed the study. Fourteen subjects reported 22 treatment-emergent adverse events (TEAEs). The severity of all TEAEs was mild, and the HNP-2006 dose was associated with the incidence of TEAEs. The most common TEAEs included nausea and dizziness, which occurred within an hour of administration. HNP-2006 was rapidly eliminated by urinary excretion with a half-life of 1.8-2.0 hours and showed a dose-proportional PK. A 2-compartment model had the best fit with the population PK analysis. CONCLUSIONS: A single intravenous dose of HNP-2006 was well-tolerated and safe up to 0.30 mmol/kg. HNP-2006 was rapidly excreted in urine and exhibited dose-independent PK profiles.

Establishment of Advanced Regulatory Innovation for Clinical Trials Transformation (ARICTT): a multi-stakeholder public-private partnership-based organization to accelerate the transformation of clinical trials.

Clinical trials have evolved with digital technologies and tend towards patient-centricity. A multi-stakeholder approach is needed to address the emerging complexities in clinical trials. In particular, the introduction of digital technologies and an emphasis on patient-centricity are the major trends in clinical trials. In response, we established a public-private partnership-based organization named Advanced Regulatory Innovation for Clinical Trials Transformation (ARICTT). Eleven organizations in total, from academia, industry, and regulatory agencies, participate in ARICTT. Based on multi-stakeholder collaboration from academia, industry, and government/regulatory bodies, we collected and prioritized current topics in clinical trials based on an internal survey. We established a three-year roadmap with axes that were termed trend, goal, structure, theme, topic, and method. In addition, we planned the development of recommendations based on real-world cases with feasibility studies. We developed appropriate organizational structure to fulfill the roadmap of ARICTT. The selected topics were decentralized clinical trials during the first year, followed by the three topics that were awarded the highest priority according to the internal survey: advances in the informed consent process, supporting sites using digital technology, and an effective recruitment strategy. We developed a case-based recommendation paper presenting an overview of the regulatory landscape and practical considerations with explanatory cases. We also designed and conducted fully decentralized trials to evaluate considerations in real-world settings for the selected topics. Overall engagement and communication were supported by the online platform and annual symposiums. In conclusion, we established a multi-stakeholder, public-private partnership-based organization to accelerate the transformation of clinical trials.

Evaluation of Food Effect on the Pharmacokinetics of Velufenacin, a New Muscarinic Receptor Antagonist, in Healthy Subjects.

Velufenacin (DA-8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open-label, single-dose, 4-sequence, 4-treatment, 4-period crossover study was conducted. Subjects received a single oral dose of velufenacin 2.5 or 5 mg in a fasted or fed (high-fat meal) state in each period with a 7-day washout. PK parameters including maximum plasma concentration (Cmax ) and area under the concentration-time curve from time 0 to the last measurable point were compared between the fed and fasted states. Twenty-seven subjects completed the study. The mean area under the concentration-time curve from time 0 to the last measurable point of the velufenacin 2.5 and 5 mg doses under the fed condition showed a 1.5- and 1.3-fold increase, respectively, compared to the fasted condition. The corresponding values for Cmax were a 2.3- and 2.0-fold increase, respectively. The time to reach Cmax was comparable regardless of the dose or food intake, showing median values of 4.5-5.0 hours. These results suggest a modest increase of velufenacin absorption by food intake. Velufenacin was generally safe and well tolerated at the 2.5 and 5 mg doses regardless of food.

Pharmacokinetics, safety and tolerability of valbenazine in Korean CYP2D6 normal and intermediate metabolizers.

Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for tardive dyskinesia treatment by the US Food and Drug Administration; its major active metabolite (NBI-98782) is a 45-fold more potent inhibitor of VMAT2 than the parent drug. This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability and the effect of cytochrome P450 2D6 (CYP2D6) genotypes to the PKs after the administration of valbenazine in Korean participants. A randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy Korean male participants. The single-dose study was conducted for both 40 and 80 mg valbenazine and the multiple dose study was conducted for 40 mg. After a 1-week washout, the 40 mg dose group participants received valbenazine 40 mg or placebo once daily for 8 days. Serial blood samples were collected up to 96 h postdose for PK analysis. The CYP2D6 genotypes of the participants were retrospectively analyzed. A total of 50 participants were randomized, and 43 and 20 participants completed the single- and multiple-dose phases of the study, respectively. After single doses, the PK characteristics of valbenazine and its metabolites were similar between the 40 and 80 mg dose groups. After multiple doses, the mean accumulation ratios of valbenazine and NBI-98782 were ~1.6 and 2.4, respectively. Plasma concentrations of valbenazine and NBI-98782 were similar between CYP2D6 normal and intermediate metabolizers. Valbenazine was well-tolerated in healthy Koreans, and its PK characteristics were similar to results previously reported in Americans.

Feasibility study for a fully decentralized clinical trial in participants with functional constipation symptoms.

Decentralized clinical trials (DCTs) leverage digital technologies to reduce dependency on study sites and intermediaries. DCT should be balanced with accessibility and data reliability while meeting regulatory requirements. Here, we conducted a pilot study for functional constipation symptoms to investigate the feasibility of DCT. The study was an open, fully remote, randomized clinical trial in participants who had functional constipation symptoms. Electronic consent was obtained remotely, and study volunteers were screened through web-based questionnaires. Subjects were randomized to either receive Lactobacillus and vitamin C supplements or vitamin C alone in a 1:1 ratio, which were delivered directly to subjects. Subjects kept track of bowel diaries daily during the 1-week baseline and 2-week treatment period using mobile applications. Bowel symptoms and the validity of the records were descriptively evaluated. A total of 30 subjects were randomized and completed the study. A total of 26.7% of subjects resided outside of the metropolitan area. Two-week Lactobacillus treatments increased the number of defecations (+0.80 vs. +0.46 times per week) and decreased the defecation time (-3.94 h vs. -1.62 h) compared to the comparator group. Overall, 67.1% of bowel diary records were completed in accordance with the schedule whereas 32.9% were not. Implementation of DCTs can facilitate geographic accessibility but should be guaranteed for data reliability. Prompt detection of errors and response using objective metrics would be required.

Analyses of the Chemical Composition of Plasma-Activated Water and Its Potential Applications for Vaginal Health.

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F-, Cl-, NO3-, SO42-; five cations: Na+, NH4+, K+, Mg2+, Ca2+) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl- concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca2+ and Mg2+), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria.

Risk improvement and adverse kidney outcomes in patients with chronic kidney disease: findings from KNOW-CKD.

BACKGROUND: Many trials have attempted to slow the progression of chronic kidney disease (CKD) by modifying specific risk factors, but without achieving satisfactory results. We aimed to evaluate the association between the degree of improvement in multiple risk factors and adverse kidney outcomes. METHODS: This was a prospective observational study of 839 patients with CKD G3-G4. The main predictors were the number of improved risk factors between baseline and year one as follows: a decrease in proteinuria, systolic blood pressure, phosphate, and uric acid, and an increase in hemoglobin and bicarbonate from the baseline status to out of the target range. The primary outcome was a composite one, including CKD progression (50% decline in eGFR or kidney replacement therapy) and all-cause death. RESULTS: Patients whose risk factors eventually improved had more unfavorable baseline profiles of the six considered factors. During 3097.8 person-years of follow-up (median 3.5 years per patient), the composite outcome occurred in 48.0% of patients (incidence rate, 13.0 per 100 person-years). Compared with an improvement of no risk factors, the adjusted HRs (95% CI) for improvement of 1 and ≥ 2 risk factors were 0.96 (0.76-1.22) and 0.53 (0.37-0.75), respectively. The association was not affected by diabetic status or CKD severity. Among the risk factors, proteinuria accounted for the greatest contribution to CKD progression. CONCLUSIONS: In patients with CKD G3-G4, improvement in multiple factors was associated with a decreased risk of CKD progression, suggesting the importance of multifactorial risk management.

Concomitant Mitochondrial Diabetes and Myopathy Mistook for Complications of Immunosuppressants After Kidney Transplant.

Posttransplant diabetes mellitus, presenile deafness, and myopathy are not commonly accompanied symptoms after kidney transplant. We report the case of a 48-year-old woman with diabetes mellitus, sensorineural hearing loss, and severe myopathy without neuropathy after deceased donor kidney transplant. ShehadamitochondrialDNApointmutation at position 3243 (A>G), and mitochondrial diseases such as maternally inherited diabetes deafness or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodeswere suspected.Diabetes andother symptoms following kidney transplant can often be overlooked as complications of immunosuppressants taken after kidney transplant. However, in patients without a known cause of their symptoms, appropriate examinations and consultation for other diseases, including genetic diseases, should be considered.

Genetic polymorphisms of hypoxia-inducible factor-1 alpha and cardiovascular disease in hemodialysis patients.

BACKGROUND: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis patients. METHODS: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1alpha were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed. RESULTS: A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5' upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03-0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12-0.72). CONCLUSION: Genetic polymorphisms of HIF-1alpha were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.

Hypoadiponectinemia and the presence of metabolic syndrome in patients with chronic kidney disease: results from the KNOW-CKD study.

BACKGROUND: In patients with chronic kidney disease, metabolic syndrome has been demonstrated to be the culprit behind diverse complications. Adiponectin is known to have anti-atherogenic and cardio-protective effects. Meanwhile, the relationship between adiponectin and metabolic syndrome in patients with chronic kidney disease has not been clarified. The aim of this study was to elucidate the relationship between adiponectin level and metabolic syndrome in patients with chronic kidney disease. METHODS: The KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease is a cohort study that enrolled subjects with chronic kidney disease throughout South Korea. From February 2011 to July 2014, data were collected from 1332 patients with chronic kidney disease. RESULTS: The mean age of the patients was 53.5 years and 803 patients (60.7%) were men. The median adiponectin level was 10.7 µg/mL and 585 (44.3%) patients had metabolic syndrome. In multiple linear regression analysis, log adiponectin was positively associated with high-density lipoprotein cholesterol levels (ß = 0.006), whereas it was negatively associated with serum albumin (ß = -0.284), triglyceride (log ß = -0.288), high sensitivity C-reactive protein (log ß = -0.058) levels and estimated glomerular filtration rate (ß = -0.005). Multiple logistic regression analysis indicated that low adiponectin level was independently associated with a higher risk of metabolic syndrome (per 1 µg/mL increase; odds ratio = 0.953, 95% confidence interval = 0.898-0.970, P < 0.001) after adjustment for multiple confounding factors. CONCLUSIONS: Hypoadiponectinemia is independently associated with the presence of metabolic syndrome in patients with chronic kidney disease.

Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.

Radiation-induced lung disease (RILD) due to radiation therapy is common. Radiologic manifestations are usually confined to the lung tissue within the radiation port and are dependent on the interval after completion of treatment. In the acute phase, RILD typically manifests as ground-glass opacity or attenuation or as consolidation; in the late phase, it typically manifests as traction bronchiectasis, volume loss, and scarring. However, the use of oblique beam angles and the development of newer irradiation techniques such as three-dimensional conformal radiation therapy can result in an unusual distribution of these findings. Awareness of the atypical manifestations of RILD can be useful in preventing confusion with infection, recurrent malignancy, lymphangitic carcinomatosis, and radiation-induced tumors. In addition, knowledge of radiologic findings that are outside the expected pattern for RILD can be useful in diagnosis of infection or recurrent malignancy. Such findings include the late appearance or enlargement of a pleural effusion; development of consolidation, a mass, or cavitation; and occlusion of bronchi within an area of radiation-induced fibrosis. A comprehensive understanding of the full spectrum of these manifestations is important to facilitate diagnosis and management in cancer patients treated with radiation therapy.

Laparoscopic internal fixation is a viable alternative option for continuous ambulatory peritoneal dialysis catheter insertion.

PURPOSE: One of the major drawbacks of peritoneal dialysis (PD) is catheter migration and dysfunction. Preventing catheter migration is one of the main concerns. We compared laparoscopic internal fixation method with open surgical method for catheter migration rates. METHODS: From January 2008 to August 2009, PD catheters were inserted by laparoscopic fixation (LF) method in 22 patients and by open surgery (OS) in 32 patients. Clinical data were reviewed retrospectively. The frequency of migration, peritonitis, and other complications were compared. Catheter and patient survival rates were also compared. RESULTS: The mean age and sex ratio were not different between groups. Mean follow-up duration was 29.1 months in LF group and 26.1 months in OS group. More patients in LF group (27.3%) had history of laparotomy than in OS group (3.1%) (P = 0.01). The mean operation time was significantly longer in LF group (101.6 ± 30.4 minutes) than in OS group (72.4 ± 26.03 minutes) (P = 0.00). The cumulative incidence of catheter migration was 65.6% in OS group and 13.6% in LF group (P = 0.00). Migration-free catheter survival was higher in LF group (P = 0.001). There were no differences in complication rates between groups. Overall catheter survival was similar (P = 0.93). Patient survival rate at 2 years was not different (P = 0.13). CONCLUSION: Laparoscopic internal fixation of continuous ambulatory peritoneal dialysis catheter significantly reduces migration rates without any addition of complications. Also, laparoscopic technique did not incur patient morbidity or mortality despite the requirement for general endotracheal anesthesia and longer operation time. Therefore, internal fixation can be afforded safely in patients with previous abdominal surgery as either a salvage or preventive measure in patients with repeated catheter migration.

Serial testing of interferon-gamma-release assays for the diagnosis of latent tuberculosis in hemodialysis patients.

INTRODUCTION: The performance of serial interferon-gamma-release assays (IGRAs) for the diagnosis of latent tuberculosis has not been studied in hemodialysis patients. METHOD: The QuantiFERON-TB-Gold In-Tube test (QFT) and T-SPOT-TB test (TSPOT) were performed 1 year after initial testing at a hemodialysis center. RESULTS: Ninety-eight patients were included in the final analysis. Positive rates for the initial tuberculin skin test (TST), QFT and TSPOT were 26.5%, 43.9% and 58.2%, respectively. The follow-up QFT and TSPOT showed positive responses in 52.0% and 53.1%. Conversion rates of the QFT and TSPOT were 20.0% and 26.8%. Reversion rates of the QFT and TSPOT were 16.3% and 29.8%; however, they decreased to 0.0% and 4.8% in patients with a concordantly positive response at the initial TST. A group at high risk for latent tuberculosis increased the risk for the TSPOT conversion [odds ratio (95% confidence interval), 7.76 (1.27-47.40)] and showed a trend of increasing the risk for the QFT conversion [1.97 (0.45-8.71)]. Reversion of both the QFT [18.92 (2.01-178.65)] and TSPOT [6.16 (1.57-24.19)] occurred more frequently in the group at low risk. CONCLUSIONS: Both conversion and reversion of the IGRAs were associated with the risk for latent tuberculosis in hemodialysis patients. However, serial IGRAs results should be interpreted cautiously due to their high variability.

Association of angiotensin II type 2 receptor gene A1818T polymorphism with progression of immunoglobulin A nephropathy in Korean patients.

We determined the relationship between the progression of immunoglobulin A nephropathy (IgAN) and the A1818T polymorphism in intron 2 of Angiotensin II type 2 receptor (AT2R) gene, which might play protective roles in the pathogenesis of IgAN. Patients with biopsy-proven IgAN were recruited from the registry of the Progressive REnal disease and Medical Informatics and gEnomics Research (PREMIER) which was sponsored by the Korean Society of Nephrology. A1818T polymorphism of AT2R gene was analyzed with PCR-RFLP method and the association with the progression of IgAN, which was defined as over 50% increase in baseline serum creatinine level, was analyzed with survival analysis. Among the 480 patients followed for more than 10 months, the group without T allele had significantly higher rates of progression of IgAN than the group with T allele (11.4% vs. 3.9%, p=0.024), although there were no significant differences in the baseline variables such as initial serum creatinine level, the degree of proteinuria, and blood pressure. In the Cox's proportional hazard model, the hazard ratio of disease progression in the patients with T allele was 0.221 (95% confidence interval for Exp(B): 0.052-0.940, p=0.041) compared to that of without T allele. In conclusion, A1818T polymorphism of AT2R gene was associated with the progression of IgAN.

MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease.

Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP- 1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN. We genotyped single nucleotide polymorphism (SNPs) in the MCP-1 G-2518A, CCR2 G46295A, RANTES C-28G and G-403A in 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of these SNPs on DN in Korean patients with type 2 DM. There were no differences in the frequencies of SNPs and the distribution of haplotypes of RANTES promoter SNPs between two groups. In conclusion, there were no associations of MCP-1, CCR2 and RANTES promoter SNPs with diabetic ESRD in Korean population. Prospective studies with clearly-defined, homogenous cohorts are needed to confirm the effect of these genetic polymorphisms on DN.

Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism.

Due to their unique capacity for self-renewal in addition to their ability to differentiate into cells of all neuronal lineages, neuronal stem cells (NSCs) are promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. However, there are few studies on immune rejection, which is one of the main problems facing successful stem cell therapy. In order to determine if human NSC might be rejected after transplantation the MHC expression level was examined in the HB1.F3 cell line, which has previously been shown to exhibit NSC properties. The results showed low expression levels of the MHC class I molecules on the surfaces of these cells. A dramatic increase in the MHC class I expression level was observed when the cells were treated with IFN-gamma, TNF-alpha, and IL-1beta, alone or in combination. The maximum induction of MHC class I protein expression was observed at above 20ng/ml IFN-gamma 48h after the treatment. The apparent additive effects of TNF-alpha and IL-1beta in combination on the maximum induction of MHC class I expression exerted by IFN-gamma treatment were not observed. The MHC class I levels elevated by IFN-gamma were sustained for 72h after withdrawing the IFN-gamma. Therefore, this study introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce the MHC class I expression level on the cell surface after infection, into HB1.F3 cells. The cells transfected with the hCMV US2, US3, US6 or US11 genes showed 20-50% reduction in the MHC class I expression level compared with the mock-transfected cells. These results suggest that NSC expresses high levels of the MHC class I proteins, and unless they are modified, might be rejected upon transplantation. In addition, the various viral stealth mechanisms can be exploited for stem cell transplantation.