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Abstract Background Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model. Methods PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 using a nonviral sysyem (2 × 106 cells/animal) were intravenously administered into cirrhotic rats. The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed. Results PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p

DNA damage repair is induced by several factors and is critical for cell survival, and many cellular DNA damage repair mechanisms are closely linked. Antioxidant enzymes that control cytokine-induced peroxide levels, such as peroxiredoxins (Prxs) and catalase (CAT), are involved in DNA repair systems. We previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) that overexpress PRL-1 (PRL-1(+)) promote liver regeneration via antioxidant effects in TAA-injured livers. However, the efficacy of these cells in regeneration and the role of Prxs in their DNA repair system have not been reported. Therefore, our objective was to analyze the Prx-based DNA repair mechanism in naïve or PRL-1(+)-transplanted TAA-injured rat livers. Apoptotic cell numbers were significantly decreased in the PRL-1(+) transplantation group versus the nontransplantation (NTx) group (p < 0.05). The expression of antioxidant markers was significantly increased in PRL-1(+) cells compared to NTx cells (p < 0.05). MitoSOX and Prx3 demonstrated a significant negative correlation coefficient (R2 = −0.8123). Furthermore, DNA damage marker levels were significantly decreased in PRL-1(+) cells compared to NTx cells (p < 0.05). In conclusion, increased Prx3 levels in PRL-1(+) cells result in an effective antioxidant effect in TAA-injured liver disease, and Prx3 is also involved in repairing damaged DNA.

Abstract Background With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan. Methods This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n = 208), Cambodia (n = 60), and Uzbekistan (n = 161) who had access to the Internet and were living abroad for at least 6 months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine. Results We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions > 3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks. Conclusions Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.

Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

Although the liver has a regenerative capacity, hepatic failure is a severe and irreversible chronic disease. Placenta-derived mesenchymal stem cells (PD-MSCs) have distinctive features, such as recycling of the placenta waste after birth, ease of accessibility, abundant cell numbers, and strong immunosuppressive properties. Previously, we reported that PD-MSCs can regenerate the liver in hepatic failure through antifibrotic and autophagic mechanisms. Many reports have investigated whether exosomes, which are formed by the budding of vesicular bodies and are emitted into the blood, from stem cells have therapeutic potential in various diseases. C-reactive protein (CRP) is produced in hepatocytes and secreted via vessels. Therefore, the objectives of this study were to compare the expression of CRP in exosomes of a hepatic failure rat model (bile duct ligation, BDL) and to evaluate the therapeutic effect by their correlation between CRP and angiogenesis depending on PD-MSC transplantation. The exosomes were analyzed in a BDL rat model with transplantation of PD-MSCs through LC-MS analysis and precipitation solution. The exosomes, CRP, and factors related to these molecules were evaluated and quantified in exosomes as well as investigated by real-time PCR, Western blot, and immunofluorescence (IF) in vivo and in vitro. CRP was present in exosomes from serum of a rat model and increased by PD-MSC transplantation. In the exosomes, CRP upregulated the factors related to the Wnt signaling pathway and angiogenesis in the BDL rat liver-transplanted PD-MSCs. Also, CRP regulated the Wnt pathway and vascularization in rat hepatocytes by interacting with endothelial cells. Therefore, our findings indicate that CRP in exosomes excreted by PD-MSCs functions in angiogenesis via the Wnt signaling pathway.

Background: Carotid artery stenosis is a dynamic process associated with an increased risk of cardiovascular events. However, knowledge of biomarkers useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events is insufficient. Therefore, the objectives of this study were to evaluate the expression of ATP binding cassette transporter 1 (ABCA1) and validate its target microRNA (miRNA) candidates in human carotid stenosis arteries to identify its potential as a biomarker. Methods: In human carotid stenosis arterial tissues and plasma, the expression of ABCA1 and its target miRNAs (miRNA-33a-5p, 33b-5p, and 148a-3p) were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Results: The expression of ABCA1 was significantly decreased in the plasma of stenosis patients, but its expression was not different in arterial tissues (p < 0.05). However, significantly more target miRNAs were secreted by stenosis patients than normal patients (p < 0.05). Interestingly, lipotoxicity induced by the oleic and palmitic acid (OAPA) or lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) dramatically enhanced the gene expression of adipogenic and inflammatory factors, whereas ABCA1 expression was significantly decreased. Conclusions: Therefore, miRNA-33a-5p, 33b-5p, and 148a-3p represent possible biomarkers of carotid artery stenosis by directly targeting ABCA1.

Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

Background We aimed to investigate the association between weight change after smoking cessation and the risk of all-cause and cause-specific mortality among middle-aged male smokers. Methods We conducted a prospective cohort study using the National Health Insurance Service National Health Screening Cohort (NHIS-HealS) database. Male Participants (n=102,403) without critical conditions aged between 40 and 79 at baseline who underwent biennial health examination were included in this study. Participants were categorized into continued smokers, recent quitters (within 4 years), long-term quitters (more than 4 years), and never-smokers based on the self-reported smoking status. Weight change was determined by the change of Body Mass Index (BMI) between the first (2002-2003) and second (2004-2005) health examination records. We followed patients from January 1, 2006 to December, 31, 2013. To assess the risk of all-cause, cancer, cardiovascular disease (CVD) mortality, and non-cancer, non-CVD mortality according to smoking cessation and weight change, we computed Hazard Ratio (HR) and 95% Confidence Interval (95% CI) using Cox proportional hazard models. Results Severity of weight gain was more prevalent among recent quitters compared to long-term quitters. After adjusting for covariates and weight change, both recent quitters (HR:0.74; 95% CI: 0.63-0.87) and long-term quitters (HR:0.53; 95% CI:0.45-0.61) had decreased risk of all-cause mortality compared to continued smokers. Similarly, both recent and long-term quitters had decreased risk of cancer, CVD, non-cancer, and non-CVD death regardless of weight change following smoking cessation. Compared to continued smokers, non-smokers also had a lower risk of overall and cause-specific death. Conclusions Post-cessation weight change did not modify the protective association of smoking cessation with reduced risk of all-cause and cause-specific death. From a public health perspective, smoking cessation program may contribute to reducing risk of death in middle-aged male smokers despite the concern on weight change after quitting smoking.

The burden of senescent hepatocytes correlates with the severity of metabolic dysfunction–associated steatotic liver disease (MASLD), but the mechanisms driving senescence and how it exacerbates MASLD are poorly understood. Hepatocytes experience lipotoxicity and become senescent when Smoothened (Smo) is deleted to disrupt Hedgehog signaling. We aimed to determine whether the secretomes of Smo-deficient hepatocytes perpetuate senescence to drive MASLD progression. RNA- Seq analysis of liver samples from human and murine cohorts with MASLD confirmed that hepatocyte populations in MASLD livers were depleted of Smo+ cells and enriched with senescent cells. When fed a choline-deficient, amino acid–restricted high-fat diet (CDA-HFD) to induce MASLD, Smo– mice had lower antioxidant markers and developed worse DNA damage, senescence, steatohepatitis, and fibrosis than did Smo+ mice. Sera and hepatocyte-conditioned medium from Smo– mice were depleted of thymidine phosphorylase (TP), a protein that maintains mitochondrial fitness. Treating Smo– hepatocytes with TP reduced senescence and lipotoxicity, whereas inhibiting TP in Smo+ hepatocytes had the opposite effect and exacerbated hepatocyte senescence, steatohepatitis, and fibrosis in CDA-HFD–fed mice. We conclude that inhibition of Hedgehog signaling in hepatocytes promoted MASLD by suppressing hepatocyte production of proteins that prevent lipotoxicity and senescence. [ABSTRACT FROM AUTHOR]

This study aimed to investigate if voluntary participation in robot-assisted gait training leads to more concentrated muscle activity patterns and clinical measure improvements. A single-participant research design study was conducted with a gradual reduction in robotic assistance during robot-assisted gait training. A child with cerebral palsy participated in 20 robot-assisted gait training sessions and two assessment sessions across 99 days. The assistive force of the Lokomat gradually reduced during repeated training. The effects of reduced assistive force on muscle activity patterns were quantitatively analyzed using a clustering algorithm and electromyography. Improvements in overall gait quality and muscle strength were measured after robot-assisted gait training. The results also showed that the number of clustered representative patterns doubled and muscle activation patterns increased when the assistance decreased by 20%, whereas full robot assistance might have hindered active participation. Since assistive force modulation can be a key in robotic rehabilitation, the proposed protocol, involving gradual assistive force reduction, demonstrates promising efficacy and allows for in-depth analysis. Therefore, further randomized clinical trials based on this study can be possible for children with cerebral palsy.

Abstract Background Distal common bile duct (dCBD) cancer is typical indication for pancreaticoduodenectomy (PD). We aimed to retrospectively evaluate surgical outcomes and investigate prognostic factors of dCBD adenocarcinoma for which PD was performed at a single institution. Methods We searched consecutive cases of dCBD adenocarcinoma undergone PD at Samsung Medical Center from 1995 to 2018. Cases with distant metastasis or palliative intent were excluded. The year in which the survival rate was dramatically improved was identified and entire years were divided into two periods for comparison. To balance between the two periods, we conducted propensity score matching (PSM) analysis using age, sex, body mass index (BMI), and American Society of Anesthesiologist score. Results Total of 804 cases were enrolled in this study. The entire period was divided into early period of 18 years and recent period of 6 years. The early and late period included 466 and 338 patients, respectively. As a result of PSM, balanced 316 patients were selected from each of the two periods. Significant improvements in surgical outcomes were identified, including shorter operation time, fewer blood loss, shorter hospitalization, and favorable overall survival. As results of multivariable analysis of independent risk factors for overall survival, older age and advanced N stage were identified, as expected. It was distinct that aggressive surgery and advanced tumor state in the early period and a lower BMI in the late period negatively affected the survival, respectively. Conclusions Surgical outcomes of dCBD cancer underwent PD was improved. There were few modifiable factors to improve survival and continuous further study is needed to detect dCBD cancer in the early stages.

Objective To investigate the factors associated with continued smoking in patients newly diagnosed with type 2 diabetes. Design Retrospective study using the Korean National Health Insurance Service-National Health Screening Cohort (2002-2013) database. Participants Male patients newly diagnosed with type 2 diabetes between 1 January 2004 and 31 December 2011. Measurement Change in smoking behaviour after the diabetes diagnosis was assessed using a self-reported questionnaire, which was administered before and after the diagnosis. To identify the factors associated with continued smoking after diabetes diagnosis, a multivariate-adjusted logistic regression was conducted using only the variables with statistical significance from the univariate analyses. Results Younger age, lower economic status, heavier smoking habit, lower Charlson Comorbidity Index and comorbid hypertension were identified as factors associated with continued smoking after the diagnosis of type 2 diabetes. Older patients (adjusted OR (aOR) 0.71, 95% CI 0.63 to 0.79) and patients with longer diabetic duration (1-2 years OR 0.88, 95% CI 0.80 to 0.98, ≥3 years OR 0.63, 95% CI 0.55 to 0.73) were more likely to quit smoking. Contrastingly, smokers in the lower economic status (aOR 1.29, 95% CI 1.18 to 1.42) and heavier smoking habit (moderate: aOR 1.53, 95% CI 1.35 to 1.72; heavy: aOR 1.90, 95% CI 1.67 to 2.17) categories were more likely to continue smoking after the diagnosis. Conclusions It is important to identify the factors associated with smoking behaviour in patients with type 2 diabetes. Recognising the factors that contribute to the vulnerability of patients to continued smoking will be helpful in developing policies and intervention strategies in future. Vulnerable patients may require intensive education and encouragement to quit smoking. We recommend physicians to take a more proactive approach, such as encouraging frequent clinical sessions for behavioural counselling and even early pharmacological interventions, when they encounter patients with the factors outlined in this study. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective: To evaluate the impact of enhanced environmental cleaning (two times per day) compared with conventional cleaning on the acquisition of carbapenem-resistant Acinetobacter baumannii (CRAB) in a highly endemic intensive care unit (ICU). Methods: The intervention consisted of alternating environmental cleaning and conventional cleaning every 3 months during the study period from July 2018 to June 2019. CRAB acquisition was assessed using incidence and prevalence rates, and colonization pressure. Results: The incidence rates of CRAB with and without enhanced cleaning were 16.3 and 13.9 cases per 1000 population, respectively; and the prevalence rates were 66.9 and 61.7 cases per 1000 population, respectively. Colonization pressure was 53.3% with enhanced cleaning and 51.3% without enhanced cleaning. No association was found between enhanced environmental cleaning and the incidence (P=0.156), prevalence (P=0.888) and colonization pressure (P=0.825) of CRAB acquisition. The ventilator utilization ratio increased the colonization pressure of CRAB acquisition (P=0.010, β coefficient=0.37). The proportion of new nurses with

Abstract. Background:. Postoperative pancreatic fistula is one of the most critical complications following pancreatic surgery. This study aimed to evaluate the utility of selective prophylactic octreotide for patients at high risk of developing postoperative pancreatic fistula. Methods:. From June 2019 to July 2020, 263 patients underwent pancreatoduodenectomy with pancreatojejunostomy at Samsung Medical Center. The individual fistula risk scores were calculated using a previously developed nomogram. The clinicopathological data of the patients were retrospectively reviewed. Results:. There were 81 patients in the low-risk group and 182 patients in the high-risk group. No statistically significant differences were found in the rates of clinically relevant postoperative pancreatic fistula between octreotide group and the control group in all patients (15.0% vs 14.7%, P = .963) and in the high-risk group (16.1% vs 23.6%, P = .206). In risk factor analysis, postoperative octreotide was not an independent risk factor for clinically relevant pancreatic fistula in all patients and the high-risk group. Drain fluid amylase levels on the first postoperative day were significantly associated with clinically relevant postoperative pancreatic fistula, regardless of the individual risk. Conclusions:. The selective use of octreotide, even in high-risk patients, showed no protective effect against pancreatic fistula. Therefore, the routine use of postoperative octreotide is not recommended.

The adequate regulation of postoperative serum glucose level (SGL) is widely accepted; however, the effects for non-diabetic patients who underwent major pancreatic surgery have not yet been established. We discerned the relevance of the immediately postoperative SGL to short-term postoperative outcomes from major pancreatic surgery in non-diabetic patients. Between January 2007 and December 2016, 2259 non-diabetic patients underwent major pancreatic surgery at four tertiary medical centers in Republic of Korea. Based on a SGL of 200 mg/dL, patients were classified into two groups by averaging the results of four SGL tests taken on the first day after surgery, and their short-term postoperative outcomes were analyzed. A 1:1 propensity score matching method was conducted to establish the high SGL group (n = 568) and the normal SGL group (n = 568). The high SGL group experienced a significantly higher rate of level C complications in the Clavien-Dindo classification (CDc) than the normal SGL group (24.1% vs. 16.5%, p = 0.002). Additionally, an SGL of more than 200 mg/dL was associated with a significantly high risk of complications above level C CDc after adjusting for other risk factors (hazard ratio = 1.324, 95% confidence interval = 1.048–1.672, p = 0.019). The regulation of SGL of less than 200 mg/dL in non-diabetic patients early after major pancreatic surgery could be helpful for reducing postoperative complications.

Saccharomycopsis fibuligera KJJ81 isolated from nuruk is an amylolytic yeast that is widely used as a microbial starter in various fermented foods. Volatile and nonvolatile metabolites of S. fibuligera KJJ81 were investigated according to different carbon sources and cultivation times using a nontargeted metabolomic approach. Partial-least-squares discriminant analysis was applied to determine the major metabolites, which were found to be closely related to the clustering and discrimination of S. fibuligera KJJ81 samples. Some volatile metabolites derived from phenylalanine, such as 2-phenylethanol, 2-phenylethyl acetate, and ethyl phenylacetate, were predominantly found in cultivation medium containing glucose (YPD medium). In addition, the level of 2-phenylethanol increased continuously with the cultivation time. In terms of nonvolatile metabolites, carbohydrates (mannose, arabitol, and mannitol), fatty acids (palmitic acid and stearic acid), organic acids (oxalic acid and succinic acid), and amino acids (isoleucine, serine, alanine, glutamic acid, glycine, proline, phenylalanine, and threonine) were the main contributors to S. fibuligera KJJ81 samples cultivated in YPD medium according to cultivation time. These results show that the formation of volatile and nonvolatile metabolites of S. fibuligera KJJ81 can be significantly affected by both the carbon sources and the cultivation time.