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  • 1
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    Online Resource
    Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 7 ( 2020-06-30), p. 2058-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-06-30), p. 2058-
    Abstract: Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3–5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9072058
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 2
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    Construction of a Vitreoscilla Hemoglobin Promoter-Based Tunable Expression System for Corynebacterium glutamicum
    MDPI AG ; 2018
    In:  Catalysts Vol. 8, No. 11 ( 2018-11-19), p. 561-
    Details
    In: Catalysts, MDPI AG, Vol. 8, No. 11 ( 2018-11-19), p. 561-
    Abstract: Corynebacterium glutamicum is an industrial strain used for the production of valuable chemicals such as L-lysine and L-glutamate. Although C. glutamicum has various industrial applications, a limited number of tunable systems are available to engineer it for efficient production of platform chemicals. Therefore, in this study, we developed a novel tunable promoter system based on repeats of the Vitreoscilla hemoglobin promoter (Pvgb). Tunable expression of green fluorescent protein (GFP) was investigated under one, four, and eight repeats of Pvgb (Pvgb, Pvgb4, and Pvgb8). The intensity of fluorescence in recombinant C. glutamicum strains increased as the number of Pvgb increased from single to eight (Pvgb8) repeats. Furthermore, we demonstrated the application of the new Pvgb promoter-based vector system as a platform for metabolic engineering of C. glutamicum by investigating 5-aminovaleric acid (5-AVA) and gamma-aminobutyric acid (GABA) production in several C. glutamicum strains. The profile of 5-AVA and GABA production by the recombinant strains were evaluated to investigate the tunable expression of key enzymes such as DavBA and GadBmut. We observed that 5-AVA and GABA production by the recombinant strains increased as the number of Pvgb used for the expression of key proteins increased. The recombinant C. glutamicum strain expressing DavBA could produce higher amounts of 5-AVA under the control of Pvgb8 (3.69 ± 0.07 g/L) than the one under the control of Pvgb (3.43 ± 0.10 g/L). The average gamma-aminobutyric acid production also increased in all the tested strains as the number of Pvgb used for GadBmut expression increased from single (4.81–5.31 g/L) to eight repeats (4.94–5.58 g/L).
    Type of Medium: Online Resource
    ISSN: 2073-4344
    URL: Article
    DOI: 10.3390/catal8110561
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662126-5
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  • 3
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    Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 10 ( 2022-10-04), p. 1980-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 10 ( 2022-10-04), p. 1980-
    Abstract: Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11101980
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
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  • 4
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    Effects of Aerobic Exercise on Tau and Related Proteins in Rats with the Middle Cerebral Artery Occlusion
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 16 ( 2020-08-14), p. 5842-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 16 ( 2020-08-14), p. 5842-
    Abstract: Although Alzheimer’s disease (AD)-like pathology is frequently found in patients with post-stroke dementia, little is known about the effects of aerobic exercise on the modifications of tau and related proteins. Therefore, we evaluated the effects of aerobic exercise on the phosphorylation and acetylation of tau and the expressions of tau-related proteins, after middle cerebral artery occlusion (MCAO) stroke. Twenty-four Sprague–Dawley rats with MCAO infarction were used in this study. The rehabilitation group (RG) received treadmill training 40 min/day for 12 weeks, whereas the sedentary group (SG) did not receive any type of training. Functional tests, such as the single pellet reaching task, rotarod, and radial arm maze tests, were performed monthly for 3 months. In ipsilateral cortices in the RG and SG groups, level of Ac-tau was lower in the RG, whereas levels of p-tauS396, p-tauS262, and p-tauS202/T205 were not significantly lower in the RG. Level of phosphorylated glycogen synthase kinase 3-beta Tyr 216 (p-GSK3βY216) was lower in the RG, but levels of p-AMPK and phosphorylated glycogen synthase kinase 3-beta Ser 9 (p-GSK3βS9) were not significantly lower. Levels of COX-2 and BDNF were not significantly different between the two groups, while SIRT1 significantly decreased in ipsilateral cortices in RG. In addition, aerobic training also improved motor, balance, and memory functions. Rehabilitation with aerobic exercise inhibited tau modification, especially tau acetylation, following infarction in the rat MCAO model, which was accompanied with the improvement of motor and cognitive functions.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21165842
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 5
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    High-Level Conversion of l-lysine into Cadaverine by Escherichia coli Whole Cell Biocatalyst Expressing Hafnia alvei l-lysine Decarboxylase
    MDPI AG ; 2019
    In:  Polymers Vol. 11, No. 7 ( 2019-07-14), p. 1184-
    Details
    In: Polymers, MDPI AG, Vol. 11, No. 7 ( 2019-07-14), p. 1184-
    Abstract: Cadaverine is a C5 diamine monomer used for the production of bio-based polyamide 510. Cadaverine is produced by the decarboxylation of l-lysine using a lysine decarboxylase (LDC). In this study, we developed recombinant Escherichia coli strains for the expression of LDC from Hafnia alvei. The resulting recombinant XBHaLDC strain was used as a whole cell biocatalyst for the high-level bioconversion of l-lysine into cadaverine without the supplementation of isopropyl β-d-1-thiogalactopyranoside (IPTG) for the induction of protein expression and pyridoxal phosphate (PLP), a key cofactor for an LDC reaction. The comparison of results from enzyme characterization of E. coli and H. alvei LDC revealed that H. alvei LDC exhibited greater bioconversion ability than E. coli LDC due to higher levels of protein expression in all cellular fractions and a higher specific activity at 37 °C (1825 U/mg protein 〉 1003 U/mg protein). The recombinant XBHaLDC and XBEcLDC strains were constructed for the high-level production of cadaverine. Recombinant XBHaLDC produced a 1.3-fold higher titer of cadaverine (6.1 g/L) than the XBEcLDC strain (4.8 g/L) from 10 g/L of l-lysine. Furthermore, XBHaLDC, concentrated to an optical density (OD600) of 50, efficiently produced 136 g/L of cadaverine from 200 g/L of l-lysine (97% molar yield) via an IPTG- and PLP-free whole cell bioconversion reaction. Cadaverine synthesized via a whole cell biocatalyst reaction using XBHaLDC was purified to polymer grade, and purified cadaverine was successfully used for the synthesis of polyamide 510. In conclusion, an IPTG- and PLP-free whole cell bioconversion process of l-lysine into cadaverine, using recombinant XBHaLDC, was successfully utilized for the production of bio-based polyamide 510, which has physical and thermal properties similar to polyamide 510 synthesized from chemical-grade cadaverine.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym11071184
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527146-5
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  • 6
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    Upregulation of Low-Density Lipoprotein Receptor of the Steroidogenesis Pathway in the Cumulus Cells Is Associated with the Maturation of Oocytes and Achievement of Pregnancy
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 9 ( 2021-09-11), p. 2389-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 9 ( 2021-09-11), p. 2389-
    Abstract: The maturation of the oocyte is influenced by cumulus cells (CCs) and associated with pregnancy rate, whereas the influencing factors have not been completely elucidated in the CCs. In this study, we identified new regulators of CCs for high-quality oocytes and successful pregnancies during assisted reproductive techniques. CCs were collected from cumulus–oocyte complexes (COCs) in young (≤33 years old) and old (≥40 years old) women undergoing intracytoplasmic sperm injection (ICSI) procedures. We screened for factors differentially expressed between young vs. old CCs and pregnancy vs. non-pregnancy using whole mRNA-seq-next-generation sequencing (NGS). We characterized the transcriptome of the CCs to identify factors critical for achieving pregnancy in IVF cycles. Women in the young and old pregnancy groups exhibited the up- and downregulation of multiple genes compared with the non-pregnancy groups, revealing the differential regulation of several specific genes involved in ovarian steroidogenesis in CCs. It was shown that the low-density lipoprotein (LDL) receptor to the steroidogenesis pathway was upregulated in CCs with higher maturity rates of oocytes in the pregnancy group. In conclusion, a higher pregnancy rate is related to the signaling pathway of steroidogenesis by the LDL receptor in infertile women undergoing IVF procedures.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10092389
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 7
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    YPL-001 Shows Various Beneficial Effects against Cigarette Smoke Extract-Induced Emphysema Formation: Anti-Inflammatory, Anti-Oxidative, and Anti-Apoptotic Effects
    MDPI AG ; 2022
    In:  Antioxidants Vol. 12, No. 1 ( 2022-12-22), p. 15-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 1 ( 2022-12-22), p. 15-
    Abstract: Inflammation, oxidative stress, and apoptosis are thought to be important causes of chronic obstructive pulmonary disease (COPD). We investigated the effect of YPL-001 (under phase 2a study, ClinicalTrials.gov identifier NCT02272634), a drug derived from Pseudolysimachion rotundum var. subintegrum, on cigarette smoke extract (CSE)-induced inflammation, the anti-oxidative pathway, and apoptosis in human lung epithelial cells and on CSE-induced emphysema in mice. YPL-001 suppressed CSE-induced expression of IL8 mRNA and protein. This was due to the reduction in NF-κB transcriptional activity by YPL-001, which resulted from the blockade of acetylation of the NF-κB subunit p65 (Lys310). Histone deacetylases (HDACs) prevent gene transcription by condensing the DNA structure and affecting NF-κB nuclear binding. YPL-001 alone increased HDAC2 activity and enhanced CSE-induced activation of HDAC2. YPL-001-induced suppression of NF-κB transcriptional activity might be caused by increased HDAC2 activity. YPL-001 increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression via both degradation of its inhibitory protein, Kelch-like ECH-associated protein 1, and an increase in de novo protein synthesis. YPL-001 increased the DNA binding activity of Nrf2. Consequently, YPL-001 upregulated the expression of Nrf2-targeted anti-oxidant genes such as NAD(P)H quinone dehydrogenase 1 and heme oxygenase 1. Moreover, YPL-001 significantly suppressed CSE-induced apoptotic cell death. In vivo study showed that CSE-induced emphysematous changes, neutrophilic inflammation, protein leakage into bronchoalveolar space, and lung cell apoptosis in mice were suppressed by YPL-001 treatment. Taken together, these results suggest that YPL-001 is a good therapeutic candidate for the treatment of COPD by blocking inflammation and apoptosis and activating the anti-oxidative pathway.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12010015
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
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  • 8
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    Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 16 ( 2021-08-10), p. 8598-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 16 ( 2021-08-10), p. 8598-
    Abstract: Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p 〈 0.05), while valsartan did not (471.2 ± 8.9 µL; p 〉 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p 〈 0.05). Transforming growth factor-β and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22168598
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Association between Reproductive Span and Sarcopenia
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 1 ( 2020-12-28), p. 154-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 1 ( 2020-12-28), p. 154-
    Abstract: Sarcopenia is defined as an age-related loss of skeletal muscle and is associated with several health disorders. Causes of sarcopenia, which included physical inactivity, alcohol, dietary habits, and smoking, have been researched. The present study was undertaken to examine the association between reproductive span and sarcopenia in Korean women. Data obtained from 2008 to 2011 Korea National Health and Nutrition Examination Surveys (KNHANES) were analyzed. We defined sarcopenia based on the cut-off values of the Foundation for the National Institutes of Health (FNIH) sarcopenia project criteria: ASM/BMI 〈 0.512 for women. Reproductive span was defined as years from menarche to menopause, and we divided the 3970 study subjects into three groups by reproductive span tertile. Multivariate logistic regression analysis was used to determine adjusted ORs for the relation between reproductive span and sarcopenia. The prevalence of sarcopenia in the study was 17.7% (704 of 3970). Multiple logistic regression analysis was performed using weighted populations. After adjusting for covariates, reproductive span was found to be inversely associated with the risk of sarcopenia [Tertile 1 = 1 (reference); Tertile 2, odds ratio (OR) = 0.927, 95% confidence interval (CI) = 0.863–0.995; Tertile 3, OR = 0.854, 95% CI = 0.793–0.915].
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph18010154
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 10
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    Patient-Reported Outcomes of Palbociclib Plus Exemestane with GnRH Agonist versus Capecitabine in Premenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer: A Prospective, Open-Label, Randomized Phase ll Trial (KCSG-BR 15-10)
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-05), p. 3265-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-05), p. 3265-
    Abstract: In the era of CDK4/6 inhibitors in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, few trials have been specifically studied to compare quality of life between palbociclib plus endocrine therapy (ET) and cytotoxic chemotherapy exclusively in premenopausal women. We aimed to evaluate differences of patient report outcomes (PROs) between palbociclib plus ET and capecitabine. PROs were assessed using EORTC QLQ-C30 at baseline, every 6 weeks, and the end of treatment. All EORTC QLQ-30 scores were maintained from baseline to the end of treatment. Patients treated palbociclib plus ET arm experienced delay in time-to-deterioration of physical functioning (HR = 0.58, 95% CI, 0.36 to 0.84, p = 0.0058), nausea and vomiting (HR = 0.48; 95% CI, 0.32 to 0.73, p = 0.0005), and diarrhea (HR = 0.42; 95% CI, 0.27 to 0.65, p = 0.001). There was a numeric trend for worsening of insomnia (HR = 1.43; 95% CI, 0.96 to 2.16, p = 0.079) and favoring of appetite loss (HR = 0.69, 95% CI, 0.44 to 1.07, p = 0.09) in the palbociclib plus ET arm. Premenopausal patients with palbociclib plus ET maintained QoL without compromising treatment efficacy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113265
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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