Mesenchymal stem cells (MSCs) have great potential for cell therapy in regenerative medicine, including liver disease. Even though ongoing research is dedicated to the goal of bringing MSCs to ...clinical applications, further understanding of the complex underlying mechanisms is required. Autophagy, a type II programmed cell death, controls cellular recycling through the lysosomal system in damaged cells or tissues. However, it is still unknown whether MSCs can trigger autophagy to enhance regeneration and/or to provide a therapeutic effect as cellular survival promoters. We therefore investigated autophagy's activation in carbon tetrachloride (CCl4)‐injured rat liver following transplantation with chorionic plate‐derived MSCs (CP‐MSCs) isolated from placenta. The expression markers for apoptosis, autophagy, cell survival, and liver regeneration were analyzed. Whereas caspase 3/7 activities were reduced (p < .05), the expression levels of hypoxia‐inducible factor‐1α (HIF‐1α) and factors for autophagy, survival, and regeneration were significantly increased by CP‐MSCs transplantation. Decreased necrotic cells (p < .05) and increased autophagic signals (p < .005) were observed in CCl4‐treated primary rat hepatocytes during in vitro coculture with CP‐MSCs. Furthermore, the upregulation of HIF‐1α promotes the regeneration of damaged hepatic cells through an autophagic mechanism marked by increased levels of light chain 3 II (LC 3II). These results suggest that the administration of CP‐MSCs promotes repair by systemically concomitant mechanisms involving HIF‐1α and autophagy. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell‐based therapeutic strategies for regenerative medicine in liver disease. STEM Cells
2013;31:1584–1596
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•The hepatocellular carcinoma risk was not statistically different between the ETV and TDF groups.•The death or liver transplant risk was not statistically different between the 2 ...groups.•These results were consistently reproduced after adjusting for confounding variables.
It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB.
From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed.
In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years PY, respectively; adjusted hazard ratio HR 0.975 p = 0.852 by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 p = 0.884 and 0.998 p = 0.988, respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 p = 0.451). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 p = 0.385 and 1.239 p = 0.360, respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05).
The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results.
It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.
The growing popularity of traditional medicine (TM) is reflected in the increasing trend for its use worldwide. Many people are turning to use TM as a complementary or integrative treatment. The aim ...of this study is to present the first nationwide report describing the use of TM in two countries (South Korea and Taiwan).
To present the TM utilization patterns between South Korea and Taiwan, we analyzed data from the National Health Insurance cohorts in each country, each of which has approximately one million inhabitants.
In total, 261,478 (25.5%) of 1,025,340 people in South Korea and 260,529 (26.8%) of 970,866 people in Taiwan used TM services at least once under the National Health Insurance in 2011. Using multivariable logistic regression, TM users in South Korea were significantly more likely to be female, 61-80 years of age and individuals with a high income, and those in Taiwan were significantly more likely to be female, 21-40 years of age and individuals with a middle income. The two countries showed similar utilization patterns in visit seasons. People visited TM clinics more frequently than TM hospitals in both countries. The most common TM treatment in South Korea was acupuncture, whereas in Taiwan, various powdered Chinese herbal preparations were the most commonly used treatment. The most common diseases for people seeking TM services were musculoskeletal system and connective tissue diseases in South Korea and Symptoms, signs, and ill-defined conditions in Taiwan.
According to the National Health Insurance database, about one fourth of the NHI beneficiaries of South Korea and Taiwan had TM use in 2011. Different TM utilization patterns existed between South Korea and Taiwan, which might be due to the differences in insurance coverage between the two countries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Carbon fiber reinforced plastic (CFRP) is currently used as a lightweight material in various parts of automobiles. However, fiber reinforced plastic (FRP) material may be damaged at the time of ...joining via mechanical bonding; therefore, adhesion is important. When bonding is conducted without surface CFRP treatment, interfacial destruction occurs during which the adhesive falls off along with the CFRP. Mechanical strength and fracture shape were investigated depending on the surface treatment (pristine, plasma treatment times, and plasma treatment times plus epoxy modified primer coating). The plasma treatment effect was verified using the contact angle and X-ray photoelectron spectroscopy. The wettability of the epoxy modified primer (EMP) coating was confirmed through surface morphology analysis, followed by observation of mechanical properties and fracture shape. Based on test data collected from 10 instances of plasma treatment, the EMP coating showed 115% higher strength than that of pristine CFRP. The adhesive failure shape also changed from interfacial failure to mixed-mode failure. Thus, applying an EMP coating during the automotive parts stage enhances the effect of CFRP surface treatment.
We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, ...nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.56 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.
Mesenchymal stem cell (MSC) therapy in chronic liver disease is associated with mitochondrial anaerobic metabolism. Phosphatase of regenerating liver-1 (PRL-1), known as protein tyrosine phosphatase ...type 4A, member 1 (PTP4A1), plays a critical role in liver regeneration. However, its therapeutic mechanism remains obscure. The aim of this study was to establish genetically modified bone marrow (BM)-MSCs overexpressing PRL-1 (BM-MSCsPRL−1) and to investigate their therapeutic effects on mitochondrial anaerobic metabolism in a bile duct ligation (BDL)-injured cholestatic rat model. BM-MSCsPRL−1 were generated with lentiviral and nonviral gene delivery systems and characterized. Compared with naive cells, BM-MSCsPRL−1 showed an improved antioxidant capacity and mitochondrial dynamics and decreased cellular senescence. In particular, mitochondrial respiration in BM-MSCsPRL−1 generated using the nonviral system was significantly increased as well as mtDNA copy number and total ATP production. Moreover, transplantation of BM-MSCsPRL−1 generated using the nonviral system had predominantly antifibrotic effects and restored hepatic function in a BDL rat model. Decreased cytoplasmic lactate and increased mitochondrial lactate upon the administration of BM-MSCsPRL−1 indicated significant alterations in mtDNA copy number and ATP production, activating anaerobic metabolism. In conclusion, BM-MSCsPRL−1 generated by a nonviral gene delivery system enhanced anaerobic mitochondrial metabolism in a cholestatic rat model, improving hepatic function.
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We successfully generated BM-MSCsPRL−1 using gene delivery systems. It improved antioxidant capacity via mitochondrial dynamics and decreased cellular senescence in injured hepatocytes. It had antifibrotic effects by enhancing anaerobic metabolism. BM-MSCsPRL−1 generated by a nonviral gene delivery system enhanced anaerobic mitochondrial metabolism in a cholestatic rat model, improving hepatic function.
Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are ...inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.
Genetic and nutritional factors contribute to the development of non-alcoholic fatty liver disease (NAFLD); however, gene-diet interactions in NAFLD development are poorly understood. In this ...case-control study, a large dataset from the Korean Genome and Epidemiology Study cohort (
= 72,299) comprising genomic data, medical records, social history, and dietary data was used. We investigated the interactions between the
rs738409 genotype and nutritional factors and their possible effect on the risk of NAFLD development in 2950 patients with NAFLD and 12,907 controls. In the
risk allele group, high protein, fat, sodium, phosphorus, niacin, and vitamin B6 intakes were associated with a decreased risk of NAFLD. In the non-risk allele group, only high fat intake was associated with a decreased risk of NAFLD. Among these nutrients, high sodium intake had a significant protective interaction with the
genotype against NAFLD (
= 0.002). Among salty foods, only kimchi had a significant protective effect against the
genotype (
= 0.012). Thus, the
genotype is differentially associated with nutritional factors. In particular, it interacts with kimchi, a fermented vegetable dish. Therefore, fermented vegetables may serve as a tailored therapeutic food for people with the
risk allele.
To date, there are few studies that have evaluated the prognostic impact of changes in abdominal obesity or weight on long-term adverse kidney outcomes in non-alcoholic fatty liver disease (NAFLD). ...We investigated the effect of changes in waist-to-hip ratio (WHR) and body weight (BW) on chronic kidney disease (CKD) development, especially in non-obese NAFLD patients. We included 6,137 participants from a community-based prospective cohort with 12-year follow-up in Korea. NAFLD patients were categorized according to time-averaged percent changes in WHR and BW (≤-5%, >-5% to <5%, and ≥5%). Compared to non-obese controls, non-obese NAFLD was significantly associated with an increased risk of incident CKD (hazard ratio HR = 1.238, 95% confidence interval CI = 1.006-1.524). In 1,563 NAFLD patients, compared to patients with minimal changes in WHR (>-5% to <5%), patients with a decreased WHR (≤-5%) had a significantly attenuated risk of CKD development (HR = 0.300; 95% CI = 0.194-0.464). Furthermore, risk reduction from decreased WHR for developing CKD remained significant in non-obese NAFLD patients (HR = 0.290; 95% CI = 0.114-0.736). In conclusion, a decrease in WHR of more than 5% significantly reduced the risk of CKD development in NAFLD patients, even in those who were non-obese. Thus, serial monitoring of WHR may be prioritized in the management of NAFLD.
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