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1.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652742

RESUMEN

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum, has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.

2.
Sci Rep ; 11(1): 4999, 2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33654225

RESUMEN

Choroidal changes have been suggested to be involved in the pathophysiology of both age-related macular degeneration (AMD) and pachychoroid spectrum diseases (PSD). To find out the choroidal characteristics of each disease groups, various groups of AMD and PSD were classified into several clusters according to choroidal profiles based on subfoveal choroidal thickness (CT), peripapillary CT, the ratio of subfoveal CT to peripapillary CT and age. We retrospectively analyzed 661 eyes, including 190 normal controls and 471 with AMD or PSDs. In the AMD groups, eyes with soft drusen or reticular pseudodrusen were belonged to the same cluster as those with classic exudative AMD (all p < 0.001). However, eyes with pachydrusen were not clustered with eyes from other AMD groups; instead, they were classified in the same cluster as eyes from the PSD group (all p < 0.001). In the PSD group, eyes with pachychoroid neovasculopathy were grouped in the same cluster of those with polypoidal choroidal vasculopathy (p < 0.001). The cluster analysis based on the CT profiles, including subfoveal CT, peripapillary CT, and their ratio, revealed a clustering pattern of eyes with AMD and PSDs. These findings support the suggestion that pachydrusen has the common pathogenesis as PSD.

3.
Plants (Basel) ; 10(2)2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33668538

RESUMEN

Soluble epoxide hydrolase (sEH) is an enzyme that is considered a potential therapeutic target in human cardiovascular disease. Triterpenes (1-4) and phenylpropanoids (5-10) were isolated from Lycopus lucidus to obtain sEH inhibitors through various chromatographic purificationtechniques. The isolated compounds were evaluated for their inhibitory activity against sEH, and methyl rosmarinate (7), martynoside (8), dimethyl lithospermate (9) and 9″ methyl lithospermate (10) showed remarkable inhibitory activity, with the IC50 values ranging from 10.6 ± 3.2 to 35.7 ± 2.1 µM. Kinetic analysis of these compounds revealed that 7, 9 and 10 were competitive inhibitors bound to the active site, and 8 was the preferred mixed type inhibitor for allosteric sites. Additionally, molecular modeling has identified interacting catalytic residues and bindings between sEH and inhibitors. The results suggest that these compounds are potential candidates that can be used for further development in the prevention and treatment for cardiovascular risk.

4.
Artículo en Inglés | MEDLINE | ID: mdl-33549539

RESUMEN

PURPOSE: The relationship between pharyngeal airway morphology and jawbone movements in skeletal Class III patients with mandibular asymmetry after orthognathic surgery remains unclear. This study was to measure the changes in pharyngeal airway morphology in skeletal Class III patients with mandibular asymmetry after bimaxillary surgery and evaluate associations between changes in pharyngeal airway morphology and skeletal movements. METHODS: In this retrospective cohort study, skeletal Class III patients who underwent bimaxillary surgery were enrolled. The predictor variable was facial symmetry status divided into 2 groups, asymmetric (Group A) and symmetric (Group B). The primary outcome variables were changes in airway parameters, including cross-sectional linear distances, cross-sectional area (CSA), minimum CSA (Min-CSA), and volume; and airway asymmetry index between the preoperative and 6-month postoperative imaging studies. Correlation analysis was performed between upper airway and skeletal changes. RESULTS: Twenty-five patients were included in this study, with 15 patients in Group A (mean age: 23.00 years; BMI: 22.83) and 10 patients in Group B (mean age: 22.30 years; BMI: 22.48). Group A showed a higher asymmetry index than Group B at T0; however, no significant differences compared to Group B at T1. The airway volume was significantly decreased in the oropharynx in Group A at T1, whereas it showed no significant differences in Group B (P < .05). Lateral movement of B point and Menton showed positive correlations with changes in Min-CSA in the oropharynx and negative correlations with changes in airway asymmetry index (P < .05). CONCLUSIONS: Pharyngeal airway exhibited an asymmetrical and constricted morphology in Group A before surgery. The airway morphology in Group A showed a tendency to adopt a symmetrical and less constricted shape after surgery. The airway space was reduced in the oropharynx in Group A after surgery. Surgical correction of mandibular asymmetry correlated with the improvement of pharyngeal airway morphology.

5.
Biomol Ther (Seoul) ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33619237

RESUMEN

Extracellular beta amyloid (Aß) plaques are the neuropathological hallmarks of Alzheimer's disease (AD). Accordingly, reducing Aß levels is considered a promising strategy for AD prevention. 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-ß-D-xylopryranoside significantly decreased the Aß production and this effect was accompanied with reduced sAPPß production known as a soluble ectodomain APP fragment through ß-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3'-O-acetyl- 24-epi-7,8-didehydrocimigenol-3-O-ß-D-xylopryranoside decreased the protein level of ß-secretases, but the protein levels of A disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3'-O-acetyl-24-epi- 7,8-didehydrocimigenol-3-O-ß-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.

6.
Curr Eye Res ; : 1-8, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33550884

RESUMEN

Purpose: To compare the regional differences in the choroidal thickness (CT) between patients with pachychoroid neovasculopathy (PNV) and classic exudative age-related macular degeneration (ceAMD).Materials and Methods: We included both eyes of patients with unilateral macular neovascularization (MNV) due to ceAMD or PNV. Unilateral eyes of normal subjects were also included as a normal control group. The regional difference in CT was defined as a difference between the macular and extramacular areas, and calculated as the ratio of subfoveal CT (SFCT) to nasal peripapillary CT (PCT).Results: In normal subjects, the choroid was 2.25 ± 0.10 times thicker at the macula than at the extramacular area. The SFCT and PCT were significantly affected by age (P < .001 and P < .001, respectively), whereas the regional difference in CT were independent of age (P = .076). Analysis of covariance including age, sex, and MNV group showed that regional difference in CT were significantly affected by sex, nasal peripapillary CT, and MNV group (P = .023, P < .001, and P < .001, respectively). The estimated marginal mean of the regional difference in CT was significantly smaller in the ceAMD group (1.671 ± 0.103) than in the normal control (2.250 ± 0.095, P = .003) and PNV groups (2.0880 ± 0.086, P < .001).Conclusions: Regional differences in CT were consistent with aging. However, the difference varied with the presence of PNV or ceAMD. Measurement of regional differences in CT provides additional information for characterizing the choroid in patients with MNV.

7.
Biol Pharm Bull ; 44(2): 245-250, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33518676

RESUMEN

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and ß-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased ß-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.

8.
Tissue Eng Regen Med ; 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33515167

RESUMEN

BACKGROUND: Autologous nerve grafts are the gold standard treatment for peripheral nerve injury treatment. However, this procedure cannot avoid sacrificing other nerves as a major limitation. The aim of the present study was to evaluate the potential of olfactory ensheathing cells (OECs) embedded in a nerve conduit. METHODS: A 10-mm segment of the sciatic nerve was resected in 21 rats, and the nerve injury was repaired with one of the following (n = 7 per group): autologous nerve graft, poly (ε-caprolactone) (PCL) conduit and OECs, and PCL conduit only. The consequent effect on nerve regeneration was measured based on the nerve conduction velocity (NCV), amplitude of the compound muscle action potential (ACMAP), wet muscle weight, histomorphometric analysis, and nerve density quantification. RESULTS: Histomorphometric analysis revealed nerve regeneration and angiogenesis in all groups. However, there were significant differences (p < 0.05) in the ACMAP nerve regeneration rate of the gastrocnemius and tibialis anterior muscles between the autologous graft (37.9 ± 14.3% and 39.1% ± 20.4%) and PCL only (17.8 ± 8.6% and 13.6 ± 5.8%) groups, and between the PCL only and PCL + OECs (46.3 ± 20.0% and 34.5 ± 14.6%) groups, with no differences between the autologous nerve and PCL + OEC groups (p > 0.05). No significant results in NCV, wet muscle weight, and nerve density quantification were observed among the 3 groups. CONCLUSION: A PCL conduit with OECs enhances the regeneration of injured peripheral nerves, offering a good alternative to autologous nerve grafts.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33417092

RESUMEN

PURPOSE: To investigate the relationship between choroidal thickness (CT) profile and clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment in polypoidal choroidal vasculopathy (PCV). METHODS: Medical records of patients diagnosed with PCV who received anti-VEGF treatment over 12 months were reviewed. Subfoveal CT (SFCT) and peripapillary CT (PCT) were measured on swept-source optical coherence tomography images. Patients were divided into various groups based on choroidal profiles including SFCT, nasal PCT (nPCT) and ratio of SFCT to nPCT (SFCT/nPCT). Clinical outcomes were compared between the thin and thick CT groups. RESULTS: A total of 65 patients with PCV patients were included. After ant-VEGF treatment, SFCT was significantly decreased after anti-VEGF treatment (P = 0.001), but nasal PCT (nPCT) was not. Clinical outcomes were not different between the thin and thick SFCT groups. Total number of injections during the 12 months was significantly fewer in the thin nPCT group (3.4 ± 1.3) than in the thick nPCT group (4.5 ± 1.8) (P = 0.020). Complete resolution after loading injections was more frequently observed in the high SFCT/nPCT ratio (> 1.9) group (87.9%) than in the low SFCT/nPCT ratio (≤ 1.90) group (59.4%) (P = 0.009). The ratio of SFCT/nPCT showed the best predictive ability for poor responders (area under curve = 0.771). CONCLUSION: These results suggest that baseline nPCT and SFCT/nPCT ratio could be a good biomarker that reflects clinical outcomes after anti-VEGF treatment in PCV.

10.
Ophthalmic Epidemiol ; : 1-8, 2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33459094

RESUMEN

Purpose: To investigate the demographic and multimodal imaging features of macular telangiectasia (MacTel) type 2 in Korea and their relationship with visual acuity and the clinical stage. Methods: A retrospective multicentre cross-sectional study was conducted in six tertiary hospitals in Korea and the study included 84 patients. Demographic data and imaging data of fundus photography, fundus autofluorescence (FAF), confocal blue-light reflectance (CBR), fluorescein angiography (FAG), and optical coherence tomography (OCT) were collected. Results: The Korean patients with MacTel type 2 were predominantly female (75%), and the mean logMAR visual acuity was 0.282 ± 0.280 at initial presentation. Most commonly presented signs were the loss of retinal transparency in fundus photographs (68.3%); increased autofluorescence in FAF (83.6%); increased blue reflectance involving the centre in CBR (68.0%); telangiectatic vessels in FAG (88.2%); and hyporeflective cavities in OCT (77.7%). The eyes diagnosed in the first half of the study period (2009-2014) showed a tendency to be diagnosed at more advanced severe stages than those diagnosed in the second half of the study period (2015-2019), using new severity scales based on FAG, FAF and OCT findings. Conclusion: The clinical features of MacTel type 2 in Korean patients assessed by newer imaging modalities suggest that Korean patients and the Caucasian-dominant population show similar presentations. This study showed that MacTel type 2 can be diagnosed in the earlier phase of the disease by using new imaging modalities and through better understanding of the disease.

11.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466670

RESUMEN

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKß, AMPK, and GSK3ß. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3ß/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.

12.
Sci Rep ; 11(1): 2025, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479464

RESUMEN

Routine prophylaxis for venous thromboembolism (VTE) in Asian IBD patients has been controversial. We aimed to estimate the risk of VTE of Asian patients at different phases of IBD by incorporating patient-specific risk factors. In this cohort study, we analyzed the National Health Insurance claims data between 2012 and 2016 for the entire Korean population. We calculated incidence rates and hazard ratios for VTE. The overall VTE risk was higher in patients with IBD [adjusted hazard ratio (aHR), 2.06; 95% confidence interval (CI), 1.66-2.55], than in controls. When we compare the risk of VTE by different disease phases, the risk of VTE was the highest during post-operation period after IBD-related bowel surgery (aHR, 39.7; 95% CI 9.87-159.3), followed by during hospitalized periods with flare (aHR, 27.2; 95% CI 14.9-49.65) and during hospitalized periods with non-flare (aHR, 16.23; 95% CI 10.71-24.58). The incidence rate (per 1000 person-years) was 15.26 during hospitalized periods with a flare and 9.83 during hospitalized periods with non-flare. According to age groups, the incidence rate (per 1000 person-years) during hospitalized periods with flare was 14.53 in young patients (20-39 years) and 34.58 in older patients (60-80 years). During hospitalized periods with non-flare, the incidence rate was 3.55 in young patients and 23.61 in older patients. The prophylaxis of VTE for Asian patients with IBD should be recommended in older patients admitted to hospital and be considered in young patients who are hospitalized with a flare.

13.
Gut Liver ; 2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33462161

RESUMEN

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a wellestablished population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions: In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy.

14.
Inflamm Bowel Dis ; 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33274375

RESUMEN

BACKGROUND: SAMP1/YitFcsJ (SAMP1) mice spontaneously develop terminal ileitis resembling human Crohn disease. SAMP1 mice have exhibited alteration of epithelial cell lineage distribution and an overall proliferation of the crypt cell population; however, it has not been evaluated whether epithelial differentiation is impaired because of dysfunction of intestinal stem cells (ISCs) or their niche factors. METHODS: Using the intestine of SAMP1 mice aged 10 to 14 weeks, morphometric alterations in the crypt-villus architecture, ISCs, crypt cells, and differentiated cells; organoid formation capacity of intestinal crypts; and niche signaling pathways were analyzed and compared with those of age-matched control AKR/J (AKR) mice. RESULTS: The ileum of SAMP1 mice showed increased depth of intestinal crypts and decreased surface area of the villi compared with those in the ileum of AKR mice. The number of ISCs in the ileal crypts did not differ between SAMP1 and AKR mice; however, the number of Paneth cells decreased and the number of transient amplifying cells increased. The organoid formation rate of the ileal crypts of SAMP1 mice decreased significantly compared with that of AKR mice. The performance of RNA sequencing for intestinal crypts found that the expression of ISC niche factors, such as Wnt3, Dll1, and Dll4, was decreased significantly in the ileal crypts of SAMP1 mice compared with those of AKR mice. Among the ISC niche signals, the Notch signaling-related genes tended to be downregulated. In particular, immunocytochemistry revealed that the expression of Paneth cell-expressing Notch ligand Dll4 was significantly decreased in the intestinal tissue and organoids of SAMP1 mice compared with those of AKR mice. CONCLUSIONS: Depletion of niche factors for ISCs contributes to the alteration of epithelial differentiation in SAMP1 mice.

15.
Prog Orthod ; 21(1): 44, 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33283252

RESUMEN

BACKGROUND: The purpose of this study is to investigate the heritability of total rotation, matrix rotation, and intramatrix rotation of the mandible in Korean monozygotic (MZ) twins, dizygotic (DZ) twins, and their siblings. MATERIALS AND METHODS: The samples consisted of 75 pairs of Korean twins (39.7 + 9.26 years; MZ group, 36 pairs; DZ group, 13 pairs; sibling group, 26 pairs). Lateral cephalograms were taken, and 13 variables related to internal and external mandible rotation were measured. Three types of occlusal planes (bisected occlusal plane, functional occlusal plane, and the MM bisector occlusal plane) were used to evaluate genetic influence on the occlusal plane. Heritability (h2) was calculated by using the intraclass correlation coefficient (ICC) and Falconer's method. RESULTS: With regard to mandibular rotation, the MZ twin group showed significantly higher ICC values compared to the DZ twin and sibling groups. The ICC mean values for 13 cephalometric measurements were 0.85 (MZ), 0.62 (DZ), and 0.52 (siblings) respectively. The heritability of the total rotation (0.48) and matrix rotation (0.5) between the MZ and DZ groups was higher than that of the intramatrix rotation (- 0.14). All of the three types of occlusal plane showed high heritability, and among the three types, the functional occlusal plane showed the highest heritability (h2 = 0.76). CONCLUSION: Based on these findings that showed a strong genetic effect on total rotation and matrix rotation, maintaining these rotations should be carefully considered in the orthodontic treatment plan, while the lower border of the mandible may be responsive to various treatments. Occlusal plane change, especially with regard to the functional occlusal plane, may not be stable due to strong genetic influences.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33328159

RESUMEN

INTRODUCTION: Systemic histaminergic activity is elevated in patients with diabetes mellitus. There are a few studies suggesting that histamine is implicated in the pathogenesis of diabetes, but the exact role of histamine in the development of diabetic retinopathy is unclear. The aim of this study was to investigate the role of histamine receptor H4 (HRH4) in the regulation of retinal pigment epithelium (RPE)-derived pro-angiogenic and anti-angiogenic factors under diabetic conditions. RESEARCH DESIGN AND METHODS: The levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), histamine and histidine decarboxylase (HDC) in the serum and vitreous samples of patients with diabetes were compared with those of patients without diabetes. The effect of hyperglycemia on expression levels of HRH4, VEGF, IL-6 and pigment epithelium-derived factor (PEDF) in the RPE was determined. The role of HRH4 in high glucose-induced regulation of VEGF, IL-6 and PEDF in ARPE-19 cells and the underlying regulatory mechanism were verified using an RNA interference-mediated knockdown study. RESULTS: The serum and vitreous levels of VEGF, IL-6, histamine and HDC were more increased in patients with diabetic retinopathy than in patients without diabetes. HRH4 was overexpressed in RPE both in vitro and in vivo. Histamine treatment upregulated VEGF and IL-6 and downregulated PEDF expression in ARPE-19 cells cultivated under hyperglycemic conditions. Hyperglycemia-induced phosphorylation of p38 and subsequent upregulation of VEGF and IL-6 and downregulation of PEDF were dampened by small interfering RNA-mediated knockdown of HRH4 in ARPE-19 cells. CONCLUSIONS: Taken together, HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.

17.
ACS Omega ; 5(45): 29453-29464, 2020 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-33225177

RESUMEN

Neoagarobiose (NA2) is the repeating disaccharide unit of agarose and possesses various promising biological activities. To identify an efficient exolytic ß-agarase required for NA2 production from agarose, the GH50A ß-agarase gene from agar-degrading Cellvibrio sp. KY-GH-1 was overexpressed as a recombinant His-tagged protein using the Escherichia coli expression system. GH50A ß-agarase that consists of 797 amino acids was able to produce predominantly NA2 from agarose at an optimal temperature and pH of 35 °C and 7.5, respectively. The enzyme was stable up to 35 °C and within a pH range of 7.0-9.0. The K m, V max, K cat, and K cat/K m values of the enzyme were 26.5 mg/mL, 16.9 U/mg, 25.2 s-1, and 1.2 × 105 s-1 M-1, respectively. The copresence of 5 mM MnSO4 and 10 mM tris(2-carboxyethyl)phosphine (TCEP) resulted in a 2.5-fold enhancement of the enzyme activity. For NA2 production, neoagaro-oligosaccharides (NAOSs) containing NA4-NA18 were preferred over agarose or agaro-oligosaccharides (AOSs) as substrates. NA2 was produced along with minor amounts of agarotriose (A3) after treatment of AOS with the enzyme, indicating that the exolytic digestion of AOS by the enzyme was initiated by releasing A3 from nonreducing ends. Enzymatic hydrolysis of 0.4% agarose (100 mL) using GH50A ß-agarase (20 µg/mL) for 4 h under optimal reaction conditions (5 mM MnSO4, 10 mM TCEP, 35 °C, 20 mM Tris-HCl, and pH 7.5) and purification of NA2 from hydrolysis products by Bio-Gel P-2 column chromatography resulted in the recovery of 216 mg of NA2 (∼54% yield from agarose). Altogether, these results suggest that the recombinant GH50A ß-agarase is useful to convert agarose to NA2.

18.
Sci Rep ; 10(1): 19841, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33199742

RESUMEN

Self-expandable metal stent (SEMS) placement has been suggested as a therapeutic modality for treating benign colorectal strictures. Covered stents are generally used, given the concerns regarding the efficacy and safety of uncovered stents. Hence, few studies have evaluated the efficacy and safety of uncovered SEMSs (UCSEMSs) in patients with refractory benign colorectal anastomotic strictures. In this study, 12 patients with postoperative benign symptomatic anastomotic strictures refractory to pneumatic dilation (range, 2-9) and transient indwelling-covered SEMSs were treated using UCSEMS. All enrolled patients were men (mean age, 61 years). Stent placement was successful in all 12 patients, and early clinical success was achieved in 11 (92%) patients. Four patients (25%) showed successful clinical outcomes without further intervention, but eight patients (75%) were clinically unsuccessful, and showed stricture recurrence or functional obstructive symptoms. Three patients underwent surgery, and the remaining five patients required repeat stent procedures. Despite the high reobstruction rate, the median follow-up period after UCSEMS placement was 16.7 months, demonstrating that UCSEMS may be able to achieve medium-term symptom relief without any complications. Therefore, UCSEMS may be an alternative option in exceptional circumstances in carefully selected patients, where invasive surgical treatments, such as stoma diversion, are not an option, thereby improving patients' quality of life.

19.
Otol Neurotol ; 2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33156237

RESUMEN

OBJECTIVE: Hearing loss is a highly penetrant phenotype in NLRP3 (Nod-Like-Receptor-Pyrin containing 3) gene-related autoinflammatory disorders. A recent study revealed potential medical treatment of hearing loss with anakinra (anti-interleukin 1 receptor antagonist) in selected cases. However, for severely aggravated hearing loss not responsive to anakinra, cochlear implantation (CI) would be the last resort for hearing rehabilitation. Outcome of CI is not clearly elucidated yet in this emerging type of hearing loss related to NLRP3-related autoinflammatory disorders, which has a systemic nature and ubiquitous distribution of resident macrophages involving the spiral ganglion neuron and the cochlear nerve. Here, we report the successful outcome of CI in NLRP3-related autoinflammatory disorder. PATIENTS: Three subjects representing each type of NLRP3-related autoinflammatory disorder: chronic infantile, neurological, cutaneous, and articular syndrome; Muckle-Wells syndrome; and DFNA34, who underwent CI for auditory rehabilitation, were recruited. INTERVENTIONS: Phenotypes as well as genotypes were reviewed in the subjects. MAIN OUTCOME MEASURES: Audiologic performances before/after CI over time were evaluated. RESULTS: All three subjects showed excellent audiological outcomes with rapid improvement of speech perception test result reaching plateau at 3 months after CI, although distribution of the disease predicted poor outcome based on theoretical analysis. CONCLUSIONS: This is the first report to present outcome of CI among subjects with a confirmed NLRP3 genetic etiology and resultant systemic inflammation, and suggests that CI is a viable treatment option in this disease entity.

20.
World J Gastrointest Oncol ; 12(9): 1005-1013, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-33005294

RESUMEN

BACKGROUND: Self-expandable metallic stent (SEMS) is widely used for malignant colorectal obstruction. Recently, SEMS has been used for palliative option for colorectal obstruction caused by extracolonic malignancy (ECM). AIM: To evaluate the efficacy of SEMS for colorectal obstruction caused by ECM, and to identify the factors associated with stent occlusion. METHODS: Seventy-two patients who were treated with uncovered SEMS insertion for malignant colorectal obstructions caused by colorectal metastasis or peritoneal seeding of ECM at Samsung Medical Center between April 2012 to March 2016 were enrolled. We analyzed technical and clinical outcomes of stent insertion, the factors associated with stent occlusion and long term outcomes after stent insertion. RESULTS: Technical success rate was determined as 90.3% with a clinical success rate of 87.7%. Stent occlusion developed in 28.1%, with a median duration of 51 d. Further, 81.3% with stent occlusion could be treated with secondary stent insertion. Clinical failure was observed to be related to the male sex (P = 0.020) and right colon obstruction (P = 0.017). Stent length ≤ 10 cm was found to be associated with stent occlusion (P = 0.003). Median survival time after stent insertion was 4.7 mo and 40.4% were able to receive their oncological treatments after stent insertion without surgery. CONCLUSION: Uncovered SEMS is effective for the treatment of colorectal obstruction caused by ECM, considering life expectancy of patients with ECM.

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