Tumor necrosis factor alpha (TNF-α) was initially recognized as a factor that causes the necrosis of tumors, but it has been recently identified to have additional important functions as a ...pathological component of autoimmune diseases. TNF-α binds to two different receptors, which initiate signal transduction pathways. These pathways lead to various cellular responses, including cell survival, differentiation, and proliferation. However, the inappropriate or excessive activation of TNF-α signaling is associated with chronic inflammation and can eventually lead to the development of pathological complications such as autoimmune diseases. Understanding of the TNF-α signaling mechanism has been expanded and applied for the treatment of immune diseases, which has resulted in the development of effective therapeutic tools, including TNF-α inhibitors. Currently, clinically approved TNF-α inhibitors have shown noticeable potency in a variety of autoimmune diseases, and novel TNF-α signaling inhibitors are being clinically evaluated. In this review, we briefly introduce the impact of TNF-α signaling on autoimmune diseases and its inhibitors, which are used as therapeutic agents against autoimmune diseases.
Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are mediated by the activation of various kinds of signaling pathways in the innate immune system. Particularly, NF-κB and NLRP3 inflammasome ...signaling are involved in the production and secretion of these cytokines. Each signaling is participated in the two steps necessary for IL-1β, a representative pro-inflammatory cytokine, to be processed into a form secreted by cells. In the priming step stimulated by LPS, pro-IL-1β is synthesized through NF-κB activation. Pro-IL-1β cleavages into mature IL-1β by formed NLRP3 inflammasome in the activation step induced by ATP. The mature form of IL-1β is subsequently secreted out of the cell, causing inflammation. Moreover, IL-6 and TNF-α are known to increase in NLRP3 inflammasome-mediated conditions. Here, we found that fucoxanthin, one of the major components of Phaeodactylum tricornutum, has an inhibitory effect on NF-κB and NLRP3 inflammasome activation induced by the combination of LPS and ATP in bone marrow-derived immune cells as well as astrocytes. Fucoxanthin, which is abundant in the EtOH fraction of Phaeodactylum tricornutum extracts, has shown to have less cell toxicity and found to decrease the production of major pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Fucoxanthin has also shown to suppress the expression of cleaved caspase-1 and the oligomerization of ASC, which are the main components of the NLRP3 inflammasome. Furthermore, phosphorylated IκBα and pro-IL-1β expression decreased in the presence of fucoxanthin, suggesting that fucoxanthin can negatively regulate the priming step of inflammasome signaling. Thus, our results provide reliable evidence that fucoxanthin may serve as a key candidate in the development of potential therapeutic agents for inflammatory diseases as well as neurodegenerative diseases caused by NF-κB and NLRP3 inflammasome activation.
Confocal and scanning electron microscopic observations have previously shown the strong bacterial association of Microcystis aeruginosa cells on their surfaces. DNA-based analyses of the associated ...bacterial communities were carried out using two M. aeruginosa strains grown in the laboratory and eight newly collected cyanobacterial bloom samples. M. aeruginosa was the most predominant species (66-100%) within the phylum Cyanobacteria. Rhizobium, Hydrogenophaga and Brevundimonas species were commonly found, and Flavobacterium species were present in all the cyanobacterial bloom samples. In total, 396 colonies from various samples were screened, revealing that most culturable bacteria belonged to the class Alphaproteobacteria (19%) including Rhizobium, Brevundimonas, and Porphyrobacter species. The genetic variation among the M. aeruginosa strains and different habitat conditions may have led to the presence of distinct bacterial populations among the tested samples. Among all the tested seven culturable isolates, Rhizobium sp. MK23 showed the best growth-promotion effect on the axenic M. aeruginosa strains. H
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was observed to be produced during the growth of M. aeruginosa PCC7806 under light conditions, this strain was more resistant to H
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when associated with Rhizobium sp. MK23. Our data suggested that Rhizobium species along with other associated bacteria might help the growth of M. aeruginosa by decomposing H
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under the aerobic growing conditions.
To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. ...For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter approximately 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.
Contrast-enhanced ultrasound (CEUS) enables the assessment of real-time renal microcirculation. This study investigated CEUS-driven parameters as hemodynamic predictors for renal outcomes in patients ...with acute kidney injury (AKI). Forty-eight patients who were diagnosed with AKI were prospectively enrolled and underwent CEUS at the occurrence of AKI. Parameters measured were the wash-in slope (WIS), time to peak intensity, peak intensity (PI), area under the time-intensity curve (AUC), mean transit time (MTT), time for full width at half maximum, and rise time (RT). The predictive performance of the CEUS-driven parameters for Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, initiation of renal replacement therapy (RRT), AKI recovery, and chronic kidney disease (CKD) progression was assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CEUS. Cortical RT (Odds ratio OR = 1.21) predicted the KDIGO stage 3 AKI. Cortical MTT (OR = 1.07) and RT (OR = 1.20) predicted the initiation of RRT. Cortical WIS (OR = 76.23) and medullary PI (OR = 1.25) predicted AKI recovery. Medullary PI (OR = 0.78) and AUC (OR = 1.00) predicted CKD progression. The areas under the ROC curves showed reasonable performance for predicting the initiation of RRT and AKI recovery. The sensitivity and specificity of the quantitative CEUS parameters were 60-83% and 62-77%, respectively, with an area under the curve of 0.69-0.75. CEUS may be a supplemental tool in diagnosing the severity of AKI and predicting renal prognosis in patients with AKI.
The 2015 outbreak of Middle East Respiratory Syndrome (MERS) in the Republic of Korea is a recent and representative occurrence of nationwide outbreaks of Emerging Infectious Diseases (EIDs). In ...addition to physical symptoms, posttraumatic stress disorder (PTSD) and depression are common following outbreaks of EID.
The present study investigated the long-term mental health outcomes and related risk factors in survivors of MERS. A prospective nationwide cohort study was conducted 12 months after the MERS outbreak at multi-centers throughout Korea. PTSD and depression as the main mental health outcomes were assessed with the Impact of Event Scale-Revised Korean version (IES-R-K) and the Patient Health Questionnaire-9 (PHQ-9) respectively.
42.9% of survivors reported PTSD (IES-R-K ≥ 25) and 27.0% reported depression (PHQ-9 ≥ 10) at 12 months post-MERS. A multivariate analysis revealed that anxiety (adjusted odds ratio aOR, 5.76; 95%CI, 1.29-25.58; P = 0.021), and a greater recognition of stigma (aOR, 11.09, 95%CI, 2.28-53.90; P = 0.003) during the MERS-affected period were independent predictors of PTSD at 12 months after the MERS outbreak. Having a family member who died from MERS predicted the development of depression (aOR, 12.08, 95%CI, 1.47-99.19; P = 0.020).
This finding implies that psychosocial factors, particularly during the outbreak phase, influenced the mental health of patients over a long-term period. Mental health support among the infected subjects and efforts to reduce stigma may improve recovery from psychological distress in an EID outbreak.
The relationship among chronic fatigue, depressive symptoms, and post-traumatic stress symptoms (PTSSs) among Middle East respiratory syndrome (MERS) survivors is poorly understood.
Of 148 survivors ...who consented to be registered and underwent assessments at 12 months (T1) and 18 months (T2) after the MERS outbreak, 72 (48.65%) were evaluated for chronic fatigue, depressive symptoms, and PTSSs based on the Impact of Event ScaleRevised (IES-R), the Patient Health Questionnaire-9 (PHQ-9), and the Fatigue Severity Scale (FSS). Data from 52 subjects, who completed both assessments, were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6).
Bootstrap analyses indicated no direct effects of T1 FSS on T2 IES-R but significant positive indirect effects of T1 FSS on T2 IESR through T1 PHQ-9 and T2 PHQ-9 (B=2.1601, SE=1.3268, 95% confidence interval=0.4250-6.1307). In other words, both T1 PHQ-9 and T2 PHQ-9 fully mediated the relationship between T1 FSS and T2 IES.
Chronic fatigue 12 months after MERS had indirect effects on prolonged PTSSs 18 months after MERS via persisting depression in MERS survivors. This finding supports the need to promote interventional programs for emerging infectious disease survivors with chronic fatigue to reduce depression and prevent prolonged PTSSs.
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•A CRISPR/Cas9-based genome editing system was constructed for M. ruber.•Disruption of MpigI or MpigI’ in M. ruber enhanced pigment production.•A Cas9-mediated mutant formed 18.5 ...times more red pigments than wild-type strain.•CRISPR/Cas9-guided engineering in useful for Monascus pigment production.
Monascus pigments have various food industry applications and are pharmacologically active. Genome sequencing-based clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has been implemented to increase pigment production in Monascus. To increase pigment production in M. ruber KACC46666, the CRISPR/Cas9 system was used to introduce mutations in two negative regulator genes (MpigI and MpigI′), among other genes involved in the Monascus pigment biosynthesis pathway. Dual single-guide RNAs were constructed to inactivate MpigI and MpigI′. After CRISPR/Cas9 inactivation, yellow, orange, and red pigment expression in the resulting △MpigI16-7 strain (among several Cas9-mediated mutants studied) was 2.5-, 12.4-, and 18.5-fold, respectively, higher than that in the wild-type strain. This study provides valuable information regarding CRISPR-guided metabolic engineering for natural colorant production.