Unregulated activation of nuclear factor-κB (NF-κB) plays a critical role in the pathogenesis of Crohn's disease. In this study, we investigated the clinical characteristics and disease outcome of ...Crohn's disease patients with varying levels of the NF-κB activation.
Crohn's disease patients who underwent surgical bowel resection were divided into two groups, based on the activation status of NF-κB. NF-κB activation was assessed by the immunoreactivity of nuclear NF-κB during immunohistochemical staining of bowel resection specimens. We compared the demographic, clinical and histologic characteristics between groups. Furthermore, the occurrence of reoperation, readmission, and medication change due to disease flare-up were investigated according to NF-κB activation status.
Among 83 Crohn's disease patients, 47 (56%) showed high NF-κB activity and 36 (44%) showed low NF-κB activity. Patients with high NF-κB activity had higher frequency of ileocolonic involvement (P = 0.028) and lower frequency of perianal involvement (P = 0.042) relative to those with low NF-κB activity. Total histologic scores were significantly higher in patients with high NF-κB activity than those with low NF-κB activity (P = 0.044). There was no significant difference in the frequency of reoperation, readmission, and medication change in relation to NF-κB activation status.
Crohn's disease patients with high NF-κB activation showed specific clinical manifestations of higher frequency of ileocolonic involvement and lower frequency of perianal involvement relative to those with low NF-κB activation. High NF-κB activity was associated with higher histologic scores. However, the NF-κB activity did not affect the outcome and disease course after surgery.
Abstract
We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May ...and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4–10 days after symptom onset.
This retrospective study examines the viral load kinetics and the correlation between disease outcome and other epidemiological parameters among 185 patients hospitalized with Middle East respiratory syndrome coronavirus (MERS-CoV) infection during the 2015 MERS-CoV outbreak in South Korea.
Abstract
Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the ...so-called “gut–skin axis.” Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (
clusterin
−/−
) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in
clusterin
−/−
mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated
clusterin
−/−
and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model.
Nogo receptor (NgR) has been shown to inhibit the migration and invasion of human glioma cells. However, little is known regarding the regulatory mechanisms of NgR in glioblastoma multiforme (GBM). ...In this study, we propose a novel mechanism that regulates the maturation process of NgR through an interaction with vimentin. The inhibition of TGFβ1 activity by LY2109761 attenuated the migration/invasion of GBM cells by upregulating cell-surface NgR. Conversely, the treatment of GBM cells with TGFβ1 suppressed NgR maturation. We showed that NgR and vimentin interact, which could be a possible mechanism for the suppression of NgR maturation. The knockdown of vimentin suppressed the migration/invasion of GBM cells through the increased maturation of NgR. Finally, TCGA (The Cancer Genome Atlas) analysis also supported the association of NgR and vimentin. The maturation of NgR is regulated by the interaction of vimentin and NgR, which attenuates the invasive activity of GBM, and might be a potential therapeutic target for brain cancer.
The different clinical manifestations of gastroesophageal reflux disease (GERD) may be influenced by associated psychological factors. We evaluated the psychological status (anxiety and depression) ...according to each subtype of GERD.
Subjects who underwent esophagogastroduodenoscopy and completed a symptom questionnaire between January 2008 and December 2011 were analyzed. The subjects were classified into the following groups: erosive reflux disease (ERD), non-erosive reflux disease (NERD), asymptomatic erosive esophagitis (AEE), and controls. Anxiety and depression were assessed using the State-Trait Anxiety Inventory and Beck Depression Inventory, respectively.
We analyzed 19 099 subjects: 16 157 (84.6%), 176 (0.9%), 1398 (7.3%), and 1368 (7.2%) in the control, ERD, NERD, and AEE groups, respectively. Multiple multinomial logistic regression revealed a significant association of increased state (adjusted OR, 1.89; 95% CI, 1.53-2.33) and trait anxiety (adjusted OR, 1.78; 95% CI, 1.34-2.35) and depression (adjusted OR, 2.21; 95% CI, 1.75-2.80) with NERD. ERD group showed a significant association only with state anxiety (adjusted OR, 2.20; 95% CI, 1.27-3.81) and depression (adjusted OR, 2.23; 95% CI, 1.18-4.22). The AEE group, however, did not show any significant association with psychological factors.
This cross-sectional study revealed that anxiety and depression levels were significantly higher in subjects with GERD (notably in the NERD) than in controls.
Alcohol consumption is generally associated with increased risk of hypertension. However, the effect of alcohol intake on the incidence of hypertension remains controversial due to inconsistent ...results across studies. We investigated the association between alcohol intake and hypertension in a Korean population.
The two studies that we evaluated herein, the CAVAS study (N = 6259) and the Ansan-Ansung study (N = 2461), were part of the Korean Genome and Epidemiology study on participants aged between 40 and 69 years who underwent community-based health checkups (2 years for the CAVAS study follow-up and 12 years for the Ansan-Ansung study follow-up). We categorized the participants into four groups based on baseline and follow-up period measurements. We found that baseline alcohol consumption increased the risk of incident hypertension in the CAVAS study HR (95% CI), low: 1.094 (0.848–1.411); intermediate: 1.661 (1.227–2.141); high: 1.723 (1.274–2.330). Intermediate and high alcohol consumption were associated with increased risk of incident hypertension in men 2.086 (1.438–3.027) for intermediate, and 1.952 (1.294–2.944) for high, but only women had increased risk of incident hypertension with high consumption 1.950 (1.100–3.455). In addition, we found a positive association between the alcohol consumption pattern (over 10 years) and the risk of incident hypertension in the Ansan-Ansung study HR (95% CI), light: 1.316 (1.126–1.539); moderate: 1.445 (1.193–1.750); heavy: 1.897 (1.488–2.419). Moderate and heavy consumption patterns carried higher risks of incident hypertension compared with never-drinking in men moderate: 1.292 (1.033–1.617); heavy: 1.703 (1.293–2.242), but women with light consumption patterns were at increased risk of incident hypertension 1.572 (1.302–1.899).
This large prospective cohort study revealed a linear association between baseline alcohol consumption, subsequent alcohol consumption patterns (over more than 10 years), and hypertension risk in the Korean population.
•We observed the relationship between alcohol intake and risk of hypertension in the large-scale prospective cohort study.•Alcohol intake was associated with the risk of hypertension in the 12-year follow-up data.•Long-term intake of alcohol increased the incidence of hypertension.
BACKGROUNDThe aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach ...including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. METHODSThis is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. RESULTSThe total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks range, 22.6-40.0 and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. CONCLUSIONOur data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.
Excessive alcohol consumption is a major public health problem in East Asian countries. Alcohol use leads to a cascade of problems including increased chances of risky behavior and a wide range of ...negative health consequences, from alcoholic liver disease to upper gastric and liver cancer. These alcohol effects are known to be influenced by ethnic variability and genetics.
In this study, subjects were administered a single dose of alcohol (0.6 g/kg for men or 0.4 g/kg for women), and blood alcohol and acetaldehyde concentrations were measured eight times over 5 hours. To investigate genetically susceptible factors to alcohol metabolism, we selected single-nucleotide polymorphisms (SNP) of genes identified by prior genetic association studies for alcohol metabolism, alcohol consumption, alcohol dependence, and related traits, and performed genotyping on all subjects (n = 104).
We identified variations in the ADH1A, SRPRB, and PGM1 genes, which are directly associated with blood alcohol or acetaldehyde concentrations. Namely, the T allele of SRPRB rs17376019 and the C allele of PGM1 rs4643 were associated with lower blood alcohol levels, while the ADH1 rs1229976 C allele group exhibited markedly higher blood acetaldehyde levels than those of the ADH1 rs1229976 T allele group.
This study demonstrates that genetic variations in ADH1A, SRPRB, and PGM1 are associated with variations in blood alcohol and acetaldehyde concentration after alcohol intake.
•Alcohol-metabolizing enzymes are influenced by ethnic variability and genetics.•Variations in SRPRB and PGM1 were associated with lower blood alcohol concentrations in subjects.•A variation in ADH1A was associated with higher blood acetaldehyde concentrations in subjects.
2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER) stress. We investigated ...whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308), and p-mTOR (Ser2481) were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.
PDF
