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  • MDPI AG  (495)
  • 1
    In: Metabolites, MDPI AG, Vol. 11, No. 8 ( 2021-07-27), p. 482-
    Abstract: Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662251-8
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  • 2
    In: Diagnostics, MDPI AG, Vol. 12, No. 7 ( 2022-07-20), p. 1757-
    Abstract: Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA 〈 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co] 1.323; adjusted R2 = 0.8445; p 〈 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg 〈 1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co] 1.331; adjusted R2 = 0.7878; p 〈 0.001) in HBeAg-positive patients with qHBsAg titers of 〈 1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co] −3.175; adjusted R2 = 0.6350; p 〈 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 3
    In: Cells, MDPI AG, Vol. 10, No. 1 ( 2021-01-01), p. 57-
    Abstract: Calcific aortic valve disease (CAVD) accompanies inflammatory cell infiltration, fibrosis, and ultimately calcification of the valve leaflets. We previously demonstrated that dipeptidyl peptidase-4 (DPP-4) is responsible for the progression of aortic valvular calcification in CAVD animal models. As evogliptin, one of the DPP-4 inhibitors displays high specific accumulation in cardiac tissue, we here evaluated its therapeutic potency for attenuating valvular calcification in CAVD animal models. Evogliptin administration markedly reduced calcific deposition accompanied by a reduction in proinflammatory cytokine expression in endothelial nitric oxide synthase-deficient mice in vivo, and significantly ameliorated the mineralization of the primary human valvular interstitial cells (VICs), with a reduction in the mRNA expression of bone-associated and fibrosis-related genes in vitro. In addition, evogliptin ameliorated the rate of change in the transaortic peak velocity and mean pressure gradients in our rabbit model as assessed by echocardiography. Importantly, evogliptin administration in a rabbit model was found to suppress the effects of a high-cholesterol diet and of vitamin D2-driven fibrosis in association with a reduction in macrophage infiltration and calcific deposition in aortic valves. These results have indicated that evogliptin prohibits inflammatory cytokine expression, fibrosis, and calcification in a CAVD animal model, suggesting its potential as a selective therapeutic agent for the inhibition of valvular calcification during CAVD progression.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 4
    In: Cells, MDPI AG, Vol. 8, No. 12 ( 2019-12-06), p. 1587-
    Abstract: Interleukin-22 (IL-22) is a cytokine with important functions in host defense and inflammatory responses and has recently been suggested to play a role in immune-inflammatory system in the context of obesity and its metabolic consequences. The specific cellular targets and mechanisms of IL-22-mediated obesity are largely unknown however. We here identified a previously unknown subset of monocyte-derived Duffy antigen receptors for chemokines (DARC)+ macrophages in epididymal fat adipose tissue and found that they are preferentially recruited into the crown-like structures of adipose tissue in the mouse upon high fat diet-induced obesity. Importantly, DARC+ macrophages highly express the IL-22 receptor (IL-22Ra1). Exposure to recombinant IL-22 shifts macrophages to an alternative M2 polarization pathway and augments DARC expression via a STAT5b signaling axis. STAT5b directly binds to the DARC promoter and a STAT5 inhibitor abrogates the IL-22-mediated induction of DARC. These M2-like DARC+ subpopulations of monocytes/macrophages were elevated in obese db/db mice compared to WT lean mice. Furthermore, subsets of CD14+ and/or CD16+ monocytes/macrophages within human peripheral blood mononuclear cell populations express DARC and the prevalence of these subsets is enhanced by IL-22 stimuli. This suggested that IL-22 is a critical cytokine that promotes the infiltration of adipose tissue macrophages, that regulate inflammatory processes. Taken together, our present findings provide important insights into the molecular mechanism by which IL-22 signal modulates DARC expression in M2-like macrophages.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661518-6
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  • 5
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 4 ( 2022-02-11), p. 935-
    Abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI 〈 60); and (3) control (FLI 〈 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
    In: Cells, MDPI AG, Vol. 9, No. 1 ( 2020-01-06), p. 131-
    Abstract: The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 7
    In: Biomedicines, MDPI AG, Vol. 11, No. 5 ( 2023-05-05), p. 1374-
    Abstract: Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A 〉 G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206–0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213–0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072–0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220–0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210–0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Cancers, MDPI AG, Vol. 13, No. 23 ( 2021-11-29), p. 6009-
    Abstract: It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p 〈 0.01). During 81.0 (interquartile range, 62.3–107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400–1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099–2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251–0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391–0.757, p 〈 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661–1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451–0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058–4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738–1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p 〈 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 9
    In: Vaccines, MDPI AG, Vol. 9, No. 12 ( 2021-11-24), p. 1379-
    Abstract: The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p 〈 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2703319-3
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  • 10
    In: Biomedicines, MDPI AG, Vol. 10, No. 7 ( 2022-06-22), p. 1481-
    Abstract: Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells. SMAD5 and RUNX-1 are involved in the TGF-β signaling pathway and contribute to advanced glycation end products (AGEs) production and vascular development. FN3KRP, a newly described gene, is also associated with vascular diseases and suggested to relate to AGEs. Therefore, in the present study, we investigated associations between RPL risk and genetic polymorphisms of SMAD5, FN3KRP, and RUNX-1 in 388 women with RPL and 280 healthy control women of Korean ethnicity. Participants were genotyped using real-time polymerase chain reaction and restriction fragment length polymorphism assay to determine the frequency of SMAD5 rs10515478 C 〉 G, FN3KRP rs1046875 G 〉 A, and RUNX-1 rs15285 G 〉 A polymorphisms. We found that women with RPL had lower likelihoods of the FN3KRP rs1046875 AA genotype (adjusted odds ratio (AOR), 0.553; p = 0.010) and recessive model (AOR, 0.631; p = 0.017). Furthermore, combination analysis showed that SMAD5 rs10515478 C 〉 G and FN3KRP rs1046875 G 〉 A mutant alleles were together associated with reduced RPL risk. These findings suggest that the FN3KRP rs1046875 G 〉 A polymorphism has a significant role on the prevalence of RPL in Korean women. Considering that it is the first study indicating a significant association between FN3KRP and pregnancy disease, RPL, our results suggest the need for further investigation of the role of FN3KRP in pregnancy loss.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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