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Purpose@#To report a case of ocular tuberculosis that first manifested as neovascular glaucoma.Case summary: A 76-year-old male visited our hospital complaining of decreased visual acuity in the left eye. He had undergone tuberculosis treatment 1 year prior, and had been cured. At the time of his visit, decreased visual acuity, increased intraocular pressure, and iris neovascularization were observed in the left eye. He was diagnosed with neovascular glaucoma and was started on treatment to lower the intraocular pressure. At the time of the visit, we also noticed vitreous opacity in both eyes. The patient did not attend his scheduled follow-up visit, but returned 2 months later complaining of decreased visual acuity in both eyes. The vitreous opacity in the retinae of both eyes had become aggravated. Diagnostic vitrectomy was performed on both eyes, and multiple yellowish-white circular lesions were observed throughout the retinae. Systemic abnormalities were suspected, and thus additional tests were performed. Bronchoalveolar lavage fluid analysis revealed recurrence of pulmonary tuberculosis, and tuberculosis treatment was recommenced. Temporary increases in ocular inflammation and deterioration were observed but improved after the addition of systemic steroids. The patient has been under observation without recurrence for about 1 year. @*Conclusions@#Ocular tuberculosis can be expressed in the form of neovascular glaucoma, so ocular tuberculosis should be suspected if there is a history of tuberculosis and abnormal retinal findings.
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Purpose@#To evaluate the reliability and validity of the Cataract-related Visual Function Questionnaire (CVFQ). @*Methods@#A prospective cross-sectional study of 141 cataract patients was conducted from March 2022 to June 2022. The questionnaire was created based on a literature review and advice from an expert panel. This study determined its construct validity, criterion validity, internal consistency, and test-retest reliability. @*Results@#The CVFQ consists of 15 items distributed among five categories: overall visual quality, overall visual function, distance vision, near vision, and glare. In the exploratory factor analysis of validity, the first three principal components explained 77.8% of the variance. The p-values in the Spearman correlation test comparing the pre- and postoperative total CVFQ score and best-corrected visual acuity (BCVA) were 0.006 and 0.004, respectively. In the reliability analysis, Cronbach’s alpha was > 0.9 for internal consistency and the p-values of each subcategory were all significant in the analysis of test-retest reliability. @*Conclusions@#Our results indicate that the CVFQ is useful for measuring the visual quality and visual function of cataract patients in Korea.
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Purpose@#To evaluate the long-term results of Boston type-I keratoprosthesis implantation in Korea. @*Methods@#Medical records of six patients (six eyes) who underwent Boston type-I keratoprosthesis implantation between August 2018 and November 2019 were retrospectively reviewed for more than 36 months. @*Results@#The mean follow-up period was 44.3 ± 7.0 months. Best corrected visual acuity (BCVA) improved significantly for all six eyes, from 2.33 ± 0.51 logarithm of the minimum angle of resolution (logMAR) to 0.67 ± 0.59 logMAR. The vision recovered immediately after the surgery in all patients. Retroprosthetic membrane developed in three of the patients, but the visual acuity remained unchanged. Anatomical success was achieved in all six eyes after Boston type-I keratoprosthesis implantation. @*Conclusions@#The long-term analysis of Boston type-I keratoprosthesis implantation showed a faster recovery and improved visual acuity compared with conventional penetrating keratoplasty. Without the use of systemic immunosuppressants, all six eyes showed long-term survival of the Boston keratoprosthesis. Boston type-I keratoprosthesis implantation may be used in patients with recurrent graft failure after keratoplasty. This was the first study investigating the long-term results of Boston keratoprosthesis implantation in Korean patients.
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Background@#Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. @*Methods@#Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. @*Results@#Of 184 patients who agreed to participate in the study, 151 were finally analyzed.Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63–0.80) for CCTA, 0.65 (95% CI, 0.56–0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70–0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55–0.71) for CCTA alone, 0.66 (0.58–0.74) for algorithm A, and 0.76 (0.68–0.82) for algorithm B. @*Conclusion@#This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.
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Purpose@#The purpose of this study was to construct the education applying the Havruta method for nursing students and to investigate the effects on self-directed learning ability, critical thinking, and learning commitment. @*Methods@#A nonequivalent control group pre-posttest design was used. The participants were 63 nursing students (experimental group, n=31; control group, n=32) at two universities. The experimental group received education applying the Havruta method for five weeks. The study was conducted from September 1 to November 30, 2022. The data were analyzed using IBM SPSS 27.0 for an χ2 test, Fisher’s exact test, independent t-test, and Mann–Whitney U-test. @*Results@#The experimental group had a significant increase in self-directed learning ability (z=-2.13, p=.033). However, there was no significant difference in critical thinking competency (t=0.64, p=.524) and learning commitment (t=0.04, p=.969) between the two groups. @*Conclusion@#The Havruta method is an effective nursing education tool for self-directed learning ability. The result of this study could be a guide for nursing professors in designing and implementing educational programs that apply the Havruta method. In the future, research that applies the Havruta method and evaluates its effectiveness in nursing education programs should be continued.
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Competencies are defined as an observable and assessable set of knowledge, skills, and attitudes. Graduation competencies, which are more comprehensive, refer to the required abilities of students to perform on-site work immediately after graduation. As graduation competencies set the goal of education, various countries and institutions have introduced them for new veterinary graduates. The Korean Association of Veterinary Medical Colleges has recently established such competencies to standardize veterinary education and enhance quality levels thereof. The purpose of this study is to describe the process of establishing graduation competencies as well as their implication for veterinary education in Korea.Graduation competencies for veterinary education in Korea comprise 5 domains (animal health care and disease management, one health expertise, communication and collaboration, research and learning, and veterinary professionalism). These are further divided into 11 core competencies, and 33 achievement standards, which were carefully chosen from previous case analyses and nation-wide surveys. Currently, graduation competencies are used as a standard for setting clear educational purposes for both instructors and students. Establishing these competencies further initiated the development of detailed learning outcomes, and of a list of basic veterinary clinical performances and skills, which is useful for assessing knowledge and skills. The establishment of graduation competencies is expected to contribute to the continuous development of Korean veterinary education in many ways. These include curriculum standardization and licensing examination reform, which will eventually improve the competencies of new veterinary graduates.
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Background@#The primary goal of scabies treatment is to eliminate mites; however, but post-scabetic itch persists in many patients. Since long-standing itching can lead to the development of other comorbidities, appropriate interventions are necessary. @*Objective@#This study aimed to investigate the effects of inappropriate (continuous or prolonged) scabicide use and oral steroids on the duration of pruritus in patients with scabies. @*Methods@#The duration of pruritus, use of oral corticosteroids, total immunoglobulin E (IgE) levels, specific IgE levels for house dust mites, and eosinophil counts were evaluated. Post-scabetic itch was defined as itching that persisted for more than 3 weeks, although scabies was no longer detected; 208 participants with post-scabetic itch were included. @*Results@#We recruited 265 participants with confirmatory diagnosis of scabies and 116 with clinical diagnosis. We treated 124 participants with scabicides based on the guidelines, whereas 257 participants were not. The type of scabicide did not affect the duration of pruritus. Scabicide overuse did not shorten the duration of pruritus; however, its prolonged use lengthened the treatment period. Although oral corticosteroids did not shorten the duration of pruritus in the patients, they were effective when the patient had post-scabetic itch. In addition, a positive correlation between the total IgE level and duration of pruritus was observed. @*Conclusion@#This study investigated the effect of treatment modality on the clinical course of scabies. Our findings suggest that overuse of scabicides might be associated with post-scabetic itch, and short-term use of oral corticosteroids may be effective in reducing its duration.
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Purpose@#To report two cases of paraproteinemic keratopathy (PK).Case summary: A 57-year-old man visited the ophthalmology clinic complaining of decreased visual acuity since 1 year earlier. White crystalline deposits were observed on both corneas and the best corrected visual acuity (BCVA) of both eyes was 1.0. After 3 months, the BCVA decreased to 0.8 in the right and 0.6 in the left. Increased corneal deposits were observed. To rule out PK, his medical records were checked. The patient had been diagnosed with lymphoplasmacytic lymphoma 3 years earlier. Diagnosing PK, the patient was referred back to the Hemato-Oncology department. After 3 months of chemotherapy, the corneal deposits decreased and BCVA returned to 1.0. A 69-year-old woman presented complaining of decreased visual acuity for 2 years. The uncorrected visual acuity (UCVA) was 0.4 in the right and finger count at 30 cm in the left. Brown deposits were observed on both corneas and lenses. The serum copper level was elevated. She was referred to the internal medicine department and diagnosed with multiple myeloma. After treatment, the laboratory results returned to normal, but the UCVA decreased to hand motion in the left. A left white cataract was noted and cataract surgery was performed. 1 month postoperatively, the BCVA was 0.9, with no change in the corneal deposits. @*Conclusions@#When there are corneal deposits, we should consider PK in the differential diagnosis. In such cases, systemic treatment is the first line. Therefore, diagnosing and referring PK patients to the internal medicine department is crucial.
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Purpose@#To study the long-term efficacy and safety of Flexivue Microlens refractive corneal inlays in Koreans for compensation of presbyopia. @*Methods@#Flexivue Microlens inlays were implanted in nine eyes at Samsung Medical Center from October 2015 to February 2018. The follow-up period was 1.95 ± 0.6 years. Pre- and postoperative near/intermediate/distant visual acuity, spherical equivalent, contrast sensitivity, defocus curve, keratometry, and patient satisfaction were evaluated retrospectively. @*Results@#The uncorrected near visual acuity (UNVA) of the operated eye increased significantly to 0.27 ± 0.10 logarithm of the minimal angle resolution (logMAR) after 6 months (p = 0.012). At the last observation, it was 0.32 ± 0.21 logMAR, which improved compared to before surgery, but the difference was not significant (p = 0.127). The binocular UNVA improved significantly to 0.19 ± 0.78 logMAR at 6 months postoperatively (p = 0.017) and to 0.21 ± 0.13 logMAR at the last observation (p = 0.028). There was no difference in the binocular uncorrected distant visual acuity (UDVA) before and after surgery, but the UDVA of the operated eye decreased significantly to 0.38 ± 0.15 logMAR at 6 months postoperatively (p = 0.007) and to 0.32 ± 0.21 logMAR at the last observation (p = 0.012). Satisfaction with near vision improved significantly after surgery; 14.3% of the patients had a score of 4 (good) or higher and 42.9% did not require near-vision glasses. In one case, the inlay was removed after 17 months due to blurred vision. @*Conclusions@#The Flexivue Microlens has a low risk of complications and is a reversible technique. However, the near vision improvement was temporary and distance vision deteriorated. In addition, the Koreans examined had relatively low satisfaction and high spectacle dependence.
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Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with ZVAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.
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Purpose@#Mobile applications are widely used in the healthcare market. This study aimed to determine whether exercise using a machine learning-based motion-detecting mobile exercise coaching application (MDMECA) is superior to video streamingbased exercise for improving quality of life and decreasing lower back pain. @*Materials and Methods@#The same 14-day daily workout program consisting of five exercises was performed by 104 participants using the MDMECA and another 72 participants using video streaming. The Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) and lower back pain scores were assess as pre- and post-workout measurements. Scores for the treatment-satisfaction subscale of the visual analog scale (TS-VAS), intention to use a disease-oriented exercise program, intention to recommend the program to others, and available expenses for a disease-oriented exercise program were determined after the workout. @*Results@#The MDMECA group showed a higher increase in SF-36 score (MDMECA, 9.10; control, 1.09; p<0.01) and a greater reduction in lower back pain score (MDMECA, -0.96; control, -0.26; p<0.01). Scores for TS-VAS, intention to use a disease-oriented exercise program, and intention to recommend the program to others were all higher (p<0.01) in the MDMECA group. However, the available expenses for a disease-oriented program were not significantly different between the two groups. @*Conclusion@#The MDMECA is more effective than video streaming-based exercise in increasing exercise adherence, improving QoL, and reducing lower back pain. MDMECAs could be promising tools of use to achieve better medical outcomes and higher treatment satisfaction.
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Purpose@#To describe successful treatment of cytomegalovirus immune recovery retinitis, with similarity to acute retinal necrosis, in patients with acquired immunodeficiency syndrome (AIDS) in the immune recovery stage.Case summary: A 37-year-old man, diagnosed with AIDS 5 years prior, visited our clinic with a chief complaint of visual disturbance in his right eye for 1 week. Slit lamp examination revealed severe inflammation; a light gray retinal lesion with a clear border was present in the inferotemporal area of the peripheral retina. Antiviral (ganciclovir) and oral steroid treatments were initiated. Blood test results indicated that the CD4+ T-cell count was 222/μL. Polymerase chain reaction analysis of anterior puncture findings showed a positive result for cytomegalovirus. Clinical findings were suggestive of acute retinal necrosis, but the patient's condition and examination were also suggestive of cytomegalovirus retinitis in the immune recovery stage. One month after treatment, retinal detachment was observed; surgery was performed. There was no recurrence for 3 years after the second operation and the patient remained in stable condition. @*Conclusions@#In the immune recovery stage, non-specific cytomegalovirus retinitis accompanied by inflammation may exhibit fundus findings similar to acute retinal necrosis. We report a rare case of cytomegalovirus immune recovery retinitis where normal vision was restored via systemic drug treatment and surgery.
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no abstract available.
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Purpose@#The study aimed to investigate how elderly gastric cancer patients do postoperatively in terms of quality of life (QoL) compared to younger patients. We also investigated how the QoL of elderly gastric cancer patients has changed over the last decade in the aging population. @*Methods@#We included 113 elderly (≥70 years) and 202 younger patients, who underwent distal gastrectomy for stage I gastric cancer during the 2010s. The European Organisation for Research and Treatment of Cancer quality of life questionnaires were used to assess preoperative and postoperative (3-month/1-year) QoL. The baseline QoL and postoperative QoL changes were compared. The elderly patients were further grouped into the early- and late-2010s groups, based on the year of surgery, and their QoL and clinical data were compared. @*Results@#The baseline QoL was significantly different on some scales (physical/role functionings, and pain/dyspnea/ dysphagia) in favor of younger patients. The postoperative QoL changes were not different with the exception of emotional functioning (1-year postoperatively) in favor of younger patients. Compared to the early-2010s group, comorbidities were more frequent, and the proportion of stage IA cancer was higher in the late-2010s group. There were no QoL differences with the exception of insomnia and financial difficulties (3-months postoperatively) in favor of the late-2010s group. @*Conclusion@#Despite baseline QoL differences, elderly gastric cancer patients did as well as younger patients in terms of postoperative QoL changes. More elderly gastric cancer patients with comorbidities are undergoing gastrectomies nowadays and it does not cause them a significant QoL disadvantage.
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Objective@#To prove the hypothesis that the parameters of intraoperative neurophysiological monitoring (IONM) during will be more deteriorated in neuromuscular scoliosis (NMS) than in adolescent idiopathic scoliosis (AIS). @*Methods@#This retrospective study reviewed the data of 69 patients (NMS=32, AIS=37) who underwent scoliosis surgery under IONM. The amplitude of motor evoked potentials (MEPs), and the amplitude and the latency of somatosensory evoked potentials (SEPs) were examined. Demographic, preoperative, perioperative and postoperative data were analyzed to determine whether they affected the IONM parameters for each group. @*Results@#Of the items analyzed, the bleeding amount was the only significant risk factor for SEP latency deterioration in the NMS group only. The amplitude of SEP and MEP did not correlate with the hemodynamic parameters. The NMS/AIS ratios of the bleeding-related parameters were higher in the order of bleeding amount/weight (2.62, p<0.01), bleeding amount/body mass index (2.13, p<0.01), and bleeding amount (1.56, p<0.01). This study suggests that SEP latency is more vulnerable than SEP or MEP amplitude in ischemic conditions during scoliosis surgery. @*Conclusion@#In NMS patients, it should be considered that the bleeding amount can have a critical effect on intraoperative electrophysiological deterioration.
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Background/Aims@#The effects of probiotics in children vary based on diseases and probiotic strains. We aim to investigate the effectiveness of Saccharomyces boulardii and lactulose for treating childhood functional constipation. @*Methods@#This open-label randomized controlled trial was conducted at 10 university hospitals in Korea. Children who were diagnosed with functional constipation were allocated to 3 groups (lactulose monotherapy, combination therapy, and S. boulardii monotherapy). The primary outcome was treatment success rate that was accordingly defined as ≥ 3 bowel movements without incontinence at week 12. The cumulative successful maintenance and drug maintenance rates without drug changes were calculated throughout the study period. We compared stool frequency, incontinence, consistency, and painful defecation at week 2 among the 3 groups. @*Results@#Overall, 187 children were assigned to the lactulose monotherapy (n = 69), combination therapy (n = 68), or S. boulardii monotherapy (n = 50) groups. The primary outcome was significantly higher in the lactulose monotherapy group (26.1%) or combination therapy group (41.2%) than in the S. boulardii monotherapy group (8.0%). The S. boulardii monotherapy group showed a significantly lower cumulative successful maintenance and drug maintenance rate than the other 2 groups. There were no significant intergroup differences in the frequency of defecation, incontinence, painful defecation, or stool consistency during the follow-up at week 2. @*Conclusion@#S. boulardii monotherapy was not superior to lactulose monotherapy or combination therapy and showed a higher drug change rate, supporting the current recommendation of probiotics in the treatment of childhood functional constipation.
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Purpose@#We report the clinical characteristics and the primary underlying diseases of patients at high risk for failure of penetrating keratoplasty (PKP) in Korea. @*Methods@#Patients at high risk of PKP failure among those who visited the ophthalmological clinics of tertiary care hospitals in Korea from April 2019 to April 2020 and who were indicated for PKP were retrospectively enrolled. We epidemiologically investigated 119 eyes of 104 patients via medical chart review. @*Results@#Herpes simplex virus (HSV) keratitis was the most common primary underlying disease (26.1%). The most common primary cause of poor bilateral visual acuity was Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (41.7%) followed by chemical burns (19.4%). Of the 119 eyes, 40.3% had a history of previous PKP and 20.2% had undergone three or more PKP. The average number of prior PKPs was 1.02 ± 1.46. Corneal neovascularization and corneal opacity were reported in 82.4 and 92.4% of cases, respectively. As the severity of these conditions increased, the eye distributions became larger. Of all patients, 47.9 and 31.9%, respectively, received the highest corneal neovascularization and corneal opacity scores. @*Conclusions@#Our study of patients at high risk of PKP failure improves our understanding of the relevant clinical characteristics and primary underlying diseases. Such patients require careful observation and aggressive treatment. Possible alternatives to PKP should be considered if PKP consistently fails. This study will aid clinicians in deciding whether to proceed to surgery if a poor postoperative prognosis is predictable.
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Background@#Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated. @*Methods@#To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD). @*Results@#Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups. @*Conclusion@#Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.
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Background@#The aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis.However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown. @*Objective@#We studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them. @*Methods@#We included 24psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction. @*Results@#AHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls. @*Conclusion@#AHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.
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Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDXMS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.