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In this study, a mixture of Platycodon grandiflorum , Pyrus serotina , Chaenomeles sinensis , and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4 . PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages.

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.

This is a cross-sectional serosurveillance study for RSV. Between June and September of 2021, a total of 150 sera were collected from 30 individuals in each age group (<5, 5-18, 19-49, 50-64, and ≥65 years). Seroprevalence was estimated using enzyme-linked immunosorbent assays targeting two stabilized prefusion F (preF; DS-Cav1 and SC-TM) and G proteins. The overall seroprevalence was low in young children and older adults, despite them having a higher risk of severe RSV infection. There was a remarkable difference in age-stratified seroprevalence rates between anti-preF and anti-G protein antibodies. Given the high disease burden and low seroprevalence in both infants and old adults, RSV vaccination would be crucial for pregnant women and people aged over 60 years., Competing Interests: The authors declare no conflicts of interest.

Codium fragile has been traditionally used in oriental medicine to treat enterobiasis, dropsy, and dysuria, and it has been shown to possess many biological properties. Atopic dermatitis (AD) is one of the types of skin inflammation and barrier disruption, which leads to chronic inflammatory skin diseases. In the current investigation, the protective effects of C. fragile extract (CFE) on anti-inflammation and skin barrier improvement were investigated. In LPS-stimulated RAW 264.7 cells, nitric oxide generation and the expression levels of interleukin (IL)-1β , IL-4 , IL-6 , iNOS , COX-2 , and tumor necrosis factor-alpha (TNF)-α were reduced by CFE. CFE also inhibited the phosphorylation of NF-κB-p65, ERK, p-38, and JNK. Additionally, CFE showed inhibitory activity on TSLP and IL-4 expression in HaCaT cells stimulated with TNF-α/interferon-gamma (IFN-γ). Enhanced expression of factors related to skin barrier function, FLG, IVL, and LOR, was confirmed. These findings implied that CFE may be used as a therapeutic agent against AD due to its skin barrier-strengthening and anti-inflammatory activities, which are derived from natural marine products.

Atopic dermatitis (AD) is a chronic inflammatory-allergic skin disorder that causes pruritic and eczematous skin lesions. Effect of Codium fragile extract (CFE) on AD has not been reported yet. In this study, inhibitory effects of CFE against skin severity scores, skin lesions, AD characteristics, and histological features of BALB/c mice with AD caused by 2,4-dinitrochlorobenzene (DNCB) were investigated. Results indicated that AD effects of CFE reduced body, skin, ear, spleen, thymus, and lymph node weights. Histopathological changes in skin reactions on the back and ears showed that CFE inhibited thickening of the epidermis and ear. Moreover, CFE reduced epidermal swelling and ear thickness compared with the DNCB group. These results suggest that CFE might be effective in alleviating AD with potential as a promising candidate for therapeutic and cosmetic treatment of inflammatory dermatitis. CFE may be useful in alleviating AD and could be a potential treatment for inflammatory dermatitis., Competing Interests: Conflict of interestThe authors have no conflicts of interest relevant to this study to disclose., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Fractionated lipids of Halocynthia aurantium (Pyuridae) have been demonstrated to possess anti-inflammatory properties. However, their modulatory properties have not been reported yet. Thus, the objective of this study was to determine immune enhancing effects of fractionated lipids from H. aurantium tunic on macrophage cells. The tunic of H. aurantium was used to isolate total lipids, which were then subsequently separated into neutral lipids, glycolipids, and phospholipids. RAW264.7 cells were stimulated with different concentrations (0.5, 1.0, 2.0, and 4.0%) of each fractionated lipid. Cytotoxicity, production of NO, expression levels of immune-associated genes, and signaling pathways were then determined. Neutral lipids and glycolipids significantly stimulated NO and PGE 2 production and expression levels of IL-1β , IL-6 , TNF-α , and COX-2 in a dose-dependent manner, while phospholipids ineffectively induced NO production and mRNA expression. Furthermore, it was found that both neutral lipids and glycolipids increased NF-κB p-65, p38, ERK1/2, and JNK phosphorylation, suggesting that these lipids might enhance immunity by activating NF-κB and MAPK signaling pathways. In addition, H. aurantium lipids-induced TNF-α expression was decreased by blocking MAPK or NF-κB signaling pathways. Phagocytic activity of RAW 264.7 cells was also significantly enhanced by neutral lipids and glycolipids. These results suggest that neutral lipids and glycolipids from H. aurantium tunic have potential as immune-enhancing materials.

Objective: Endovascular aneurysm repair (EVAR) has been used worldwide to treat abdominal aortic aneurysms (AAAs). Outcomes after EVAR within and outside the instruction for use (IFU) remain controversial. We analyzed long-term outcomes of EVAR within-the-IFU compared with that outside-the-IFU and baseline clinical/anatomical characteristics that influence outcomes of EVAR., Methods: The study included 546 patients who underwent EVAR for infrarenal AAA from 1997 to 2021 at 2 Korean medical centers. The primary endpoint was graft-related adverse events (GRAEs), including type 1 or 3 endoleak, reintervention (included open conversion), aneurysm sac enlargement, aneurysm-related mortality (ARM), rupture, stent-graft migration, and stent thrombotic occlusion., Results: The patients who underwent EVAR outside the IFU were 287 (52.6%). A neck angle of >60° was most common outside the IFU criteria (n=146, 50.9%). This study revealed that patients outside the IFU had a higher rate of GRAEs compared with patients within the IFU (hazard ratio [HR]: 1.879; 95% confidence interval [CI]: 1.045-2.386). A neck angle of >60° was a significant risk factor for GRAEs (adjusted HR: 2.229; 95% CI: 1.418-3.503), type 1 or 3 endoleak (adjusted HR: 2.640; 95% CI: 1.343-5.189), and reintervention (adjusted HR: 1.891; 95% CI: 1.055-3.388)., Conclusions: Our study revealed EVAR with outside the IFU was associated with increased GRAEs, mainly attributed to endoleak and ARM, compared with EVAR with within the IFU. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak, and reintervention., Clinical Impact: Our study revealed endovascular aneurysm repair (EVAR) with outside-the-instruction for use (IFU) was associated with increased graft-related adverse events (GRAEs) compared with EVAR with within-the-IFU. In the low-risk population, the incidence of GRAEs and Aneurysm related mortality were higher in the outside-the-IFU group rather than within-the-IFU group. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak and reintervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The immune-enhancing activity of the combination of Platycodon grandiflorum and Salvia plebeian extracts (PGSP) was evaluated through macrophage activation using RAW264.7 cells. PGSP (250-1000 μg/mL) showed a higher release of NO in a dose-dependent manner. The results showed that PGSP could significantly stimulate the production of PGE2, COX-2, TNF-α, IL-1β, and IL-6 in RAW264.7 cells and promote iNOS, COX-2, TNF-α, IL-1β, IL-4, and IL-6 mRNA expression. Western blot analysis demonstrated that the protein expression of iNOS and COX-2 and the phosphorylation of ERK, JNK, p38, and NF-κB p65 were greatly increased in PGSP-treated cells. PGSP also promoted the phagocytic activity of RAW264.7 cells. All these results indicated that PGSP might activate macrophages through MAPK and NF-κB signaling pathways. Taken together, PGSP may be considered to have immune-enhancing activity and might be used as a potential immune-enhancing agent., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines., Methods: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP., Results: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus , serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease ( P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961)., Conclusion: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Introduction: Patent foramen ovale (PFO) closure is performed in selected patients with cryptogenic stroke to prevent recurrence. The prognosis of patients with uncrossable PFO after failed guidewire or catheter passage during the procedure remains unknown. We compared the long-term prognosis between uncrossable PFO and successful PFO closure in patients with high-grade PFO shunts., Methods: We analyzed patients who underwent PFO closure for stroke or transient ischemic attack (TIA) prevention at Gachon University Gil Medical Center between April 2010 and March 2022. The primary outcome was a composite of recurrent stroke or TIA. Secondary outcomes included stroke, TIA, all-cause death, and a composite of stroke, TIA, and all-cause death., Results: Of 286 patients, 245 were included in the analysis after excluding those with transseptal puncture technique usage or concurrent atrial septal defect. Among them, 82 had uncrossable PFO, and 163 underwent successful PFO closure. Large shunts were more prevalent in the PFO closure group compared to the uncrossable PFO group (62.0% vs. 34.1%, P  < 0.001), and resting shunts were also more common in the PFO closure group (17.8% vs. 2.4%, P  < 0.001). Stroke or TIA occurred in 2 patients (2.4%) in the uncrossable PFO group and 8 patients (4.9%) in the PFO closure group (hazard ratio, 1.44; 95% confidence interval, 0.30-6.81; P  = 0.647). Additionally, no disparities in the occurrence of stroke or TIA were found in subgroups divided by baseline characteristics, RoPE score, or shunt grade., Conclusion: Clinical outcomes for patients with uncrossable PFO seem similar to those with successful PFO closure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shin, Jang, Won, Yang, Kim, Lee, Seo, Kim, Oh, Chung, Moon and Kang.)

Background and Objectives : Polymer-free ultrathin strut sirolimus- and probucol-eluting stents (PF-SES) are recognized as safe and effective in diverse patient populations, although the implications of post-dilation during stent implantation remain underexamined. Materials and Methods : In this study, patients implanted with PF-SES at Gachon University Gil Medical Center between December 2014 and February 2018 were evaluated. Major adverse cardiovascular events (MACE), encompassing nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death were identified as primary outcomes, with secondary outcomes including target vessel revascularization (TVR), target lesion revascularization (TLR), and in-stent restenosis (ISR). Results : Of the 384 initial patients, 299 were considered eligible for analysis. The groups, delineated by those undergoing post-dilation (143 patients) and those not (156 patients), exhibited comparable rates of primary outcomes [hazard ratio (HR), 2.17; 95% confidence interval (CI), 0.40 to 11.87; p = 0.37]. The outcomes remained consistent irrespective of the post-dilation status and were similarly unaffected in multivariate analyses (HR, 2.90; 95% CI, 0.52 to 16.34; p = 0.227). Conclusions : These results suggest that the clinical outcomes of patients with post-dilation were similar to that of those without post-dilation in those with the polymer-free sirolimus- and probucol-eluting stents.

A lipid extract was obtained from eggs of the sailfin sandfish, Arctoscopus japonicus . Immunostimulatory effects of A. japonicus lipids incorporated with PEG6000 (AJ-PEG) on immunosuppressed mice treated with cyclophosphamide (CY) were investigated. AJ-PEG was administered orally to mice at different concentrations of 25 to 100 mg/kg body weight (BW). CY was injected to mice intraperitoneally at 80 mg/kg BW. Administration of AJ-PEG significantly increased the spleen index of CY-treated mice. AJ-PEG also stimulated the proliferation of splenic lymphocytes and natural killer (NK) activity. Immune-associated cytokines such as IL-1β , IL-2 , IL-4 , IL-6 , TNF-α , and IFN-γ as well as TLR4 were overexpressed in splenic lymphocytes. Furthermore, AJ-PEG significantly increased splenic CD4+ and CD8+ T lymphocytes. In peritoneal macrophages, AJ-PEG administration improved proliferation, nitric oxide (NO) production, and phagocytosis. It also upregulated iNOS , COX-2 , IL-1β , IL-6 , and TNF-α expression. Taken together, these results suggest that AJ-PEG can be used in animal models with immunosuppressive conditions as a potent immunomodulatory agent.

Korean ginseng ( Panax ginseng C. A. Meyer), a member of the Araliaceae family, is known as a traditional medicinal plant to have a wide range of health properties. Polysaccharides constitute a major component of Korean ginseng, and its berries exhibit immune-modulating properties. The purpose of this study was to investigate the immune effects of crude polysaccharide (GBPC) extracted from Korean ginseng berry on peritoneal macrophages in mice with cyclophosphamide (CY)- induced immunosuppression. BALB/c mice were divided into eight groups: normal control, normal control + CY, levamisole + CY, ginseng + CY, and four concentrations of 50, 100, 250, and 500mg/kg BW/day of GBPC + CY. Mice were orally administered with samples for 10 days. Immunosuppression was established by treating mice with CY (80 mg/kg BW/day) through intraperitoneal injection on days 4 to 6. The immune function of peritoneal macrophages was then evaluated. Oral administration of 500mg/kg BW/day GBPC resulted in proliferation, NO production, and phagocytosis at 100%, 88%, and 91%, respectively, close to the levels of the normal group (100%) of peritoneal macrophages. In CY-treated mice, GBPC of 50-500 mg/kg BW/day also dose-dependently stimulated the proliferation, NO production, and phagocytosis at 56-100%, 47-88%, and 53-91%, respectively, with expression levels of immune-associated genes, such as iNOS , COX-2 , IL-1β , IL-6 , and TNF-α , of about 0.32 to 2.87-fold, compared to those in the CY group. GBPC could be a potential immunomodulatory material to control peritoneal macrophages under an immunosuppressive condition.

There are no data available comparing the real-world, long-term clinical outcomes of drug-eluting balloon (DEB) angioplasty and drug-eluting stent (DES) implantation in DES in-stent restenosis (ISR) lesions. We aimed to compare the real-world, long-term data available between DEBs and DESs in DES-ISR lesions. We analyzed consecutive DES-ISR lesions (225 lesions from 205 patients; male: 66.3%; mean age: 62.4 years) treated with either DEB or DES. The primary endpoint was target lesion revascularization (TLR), and the primary safety endpoint was the lesion-oriented composite outcome (LOCO). The LOCO is composed of cardiac death, myocardial infarction, and target lesion thrombosis during follow-up. During the 7-year follow-up period, TLR did not differ significantly between the DEB ( n = 108) and the DES groups ( n = 117) (HR: 1.07; 95% CI: 0.59-1.93, p = 0.83). The LOCO was significantly lower in the DEB group compared to the DES group (HR: 0.40; 95% CI: 0.16-0.98, p = 0.04), which was mainly driven by the lower levels of myocardial infarction (HR: 0.24; 95% CI: 0.06-0.94, p = 0.04) and the absence of target lesion thrombosis in the DEB group (vs. DES group 6%, p = 0.02). Additionally, cardiac death was found to be similar between the DEB and DES groups (HR: 0.56; 95% CI: 0.18-1.75, p = 0.32). DEB angioplasty showed favorable safety with a similar efficacy to that of DES implantation in DES-ISR lesions during the long-term follow-up period.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea., Methods: PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases., Results: Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37-62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease., Conclusions: This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2023. The Korean Society of Cardiology.)

Background: Whether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised., Methods: A prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3-4 weeks, 3 months, and 6 months after booster vaccination., Results: A total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections., Conclusion: Booster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hyun, Jang, Park, Heo, Seo, Nham, Yoon, Seong, Noh, Cheong, Kim, Yoon, Seok, Kim, Park and Song.)

Fatty acids extracted from the Halocynthia aurantium gonad (HAGF) were shown to be primarily composed of the highest concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at 41% and 17% of total fatty acids, respectively. In the present study, HAGF were examined for their immunostimulant and anti-inflammatory effects on RAW264.7 macrophage cells. HAGF were found to significantly boost nitric oxide (NO) production and increase the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF)-α expression in a dose-dependent manner. Moreover, the phosphorylation of c-Jun N -terminal kinase/stress-activated protein kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and nuclear factor κB (NF-κB) p65 was up-regulated by the stimulation of RAW264.7 cells with HAGF. When lipopolysaccharide (LPS)-stimulated the macrophages, they also exhibited anti-inflammatory activity via decreasing NO production and immune-related gene expression, Cluster of differentiation (CD) 86 expression, and protein levels in the NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways. Overall, these results indicate that HAGF exert immune-modulatory effects in macrophages.

Background: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions., Methods and results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (p interaction =0.008) and side branch calcification (p interaction =0.010)., Conclusions: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

Halocynthia aurantium is a marine organism that has been considered a promising source for bio-functional materials. Total lipids were extracted from H. aurantium tunic, and then they were separated into neutral lipids, glycolipids, and phospholipids. In the present study, fatty acid profiles of three lipids and their anti-inflammatory effects in RAW264.7 cells were investigated. Among the lipid classes, phospholipids showed the diversity of fatty acid constituents, compared with the glycolipids and neutral lipids. Three lipids contain different contents of fatty acids depending on the kinds of lipids. The most contents were saturated fatty acids (SFAs, 53-69% of the fatty acids) and monounsaturated fatty acids (MUFAs, 15-17% of fatty acids) and polyunsaturated fatty acids (PUFAs, 14-32% of fatty acids) are followed. H. aurantium lipids not only dose-dependently inhibited nitric oxide production but also reduced the expression of inflammatory cytokine genes such as TNF-α, IL-1β, and IL-6 in LPS-stimulated macrophages. It was also demonstrated that the expression of COX-2 was dose-dependently suppressed. Moreover, H. aurantium lipids decreased phosphorylation of NF-κB p-65, p38, ERK1/2, and JNK, suggesting that three lipids from H. aurantium tunic provide anti-inflammatory effects through NF-κB and MAPK signaling. These results indicate that H. aurantium is a potential source for anti-inflammation., Competing Interests: The authors declare no conflict of interest.

Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Even more surprisingly, a paradoxical increase of all-cause and cardiovascular (CV) mortality with increased adiponectin levels was reported. The adiponectin-mortality paradox has been explained by some groups asserting that adiponectin secretion is promoted by elevated natriuretic peptides (NP). Other groups have proposed that adiponectin is elevated due to adiponectin resistance in subjects with metabolic syndrome or heart failure (HF). However, there is no unifying theory that can clearly explain this paradox. In patients with HF with reduced ejection fraction (HFrEF), stretched cardiomyocytes secrete NPs, which further promote release of adiponectin from adipose tissue, leading to adiponectin resistance. On the other hand, adiponectin biology may differ in patients with heart failure with preserved ejection fraction (HFpEF), which constitutes 50% of all of HF. Most HFpEF patients are obese, which exerts inflammation and myocardial stiffness, i.e. likely to prevent myocardial stretch and subsequent NP release. This segment of the patient population may display different adiponectin biology from its HFrEF counterpart. Dissecting the adiponectin-mortality relationship in terms of different HF subtypes may help to comprehensively understand this paradox. Mendelian randomization (MR) analyses claimed that adiponectin levels are not causally related to CAD or metabolic syndrome. Results from MR studies, however, should be interpreted with great caution because the underlying history of CAD or CHF was not taken into account in these analyses, an issue that may substantially confound the results. Here, we discuss many aspects of adiponectin; cardiometabolic traits, therapeutic interventions, and the ongoing debate about the adiponectin paradox, which were recently described in basic, epidemiologic, and clinical studies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Salmonella enterica is a leading cause of food-borne diseases in humans worldwide, resulting in severe morbidity and mortality. They are carried asymptomatically in the intestine or gallbladder of livestock, and are transmitted predominantly from animals to humans via the fecal-oral route. Thus, the best preventive strategy is to preemptively prevent transmission to humans by vaccinating livestock. Live attenuated vaccines have been mostly favored because they elicit both cellular and humoral immunity and provide long-term protective immunity. However, developing these vaccines is a laborious and time-consuming process. Therefore, most live attenuated vaccines have been mainly used for phenotypic screening using the auxotrophic replica plate method, and new types of vaccines have not been sufficiently explored. In this study, we used Radiation-Mutation Enhancement Technology (R-MET) to introduce a wide variety of mutations and attenuate the virulence of Salmonella spp. to develop live vaccine strains. The Salmonella Typhimurium, ST454 strain (ST WT) was irradiated with Cobalt 60 gamma-irradiator at 1.5 kGy for 1 h to maximize the mutation rate, and attenuated daughter colonies were screened using in vitro macrophage replication capacity and in vivo mouse infection assays. Among 30 candidates, ATOMSal-L6, with 9,961-fold lower virulence than the parent strain (ST454) in the mouse LD 50 model, was chosen. This vaccine candidate was mutated at 71 sites, and in particular, lost one bacteriophage. As a vaccine, ATOMSal-L6 induced a Salmonella -specific IgG response to provide effective protective immunity upon intramuscular vaccination of mice. Furthermore, when mice and sows were orally immunized with ATOMSal-L6, we found a strong protective immune response, including multifunctional cellular immunity. These results indicate that ATOMSal-L6 is the first live vaccine candidate to be developed using R-MET, to the best of our knowledge. R-MET can be used as a fast and effective live vaccine development technology that can be used to develop vaccine strains against emerging or serotype-shifting pathogens., Competing Interests: Authors SJB and HKJ are employed by CTCVAC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Jang, Song, Ahn, Han, Bang, Jung, Hur and Seo.)

Aims: To investigate anti-inflammatory effects of Lactobacillus reuteri LM1071 in lipopolysaccharides (LPS)-induced inflammation RAW264.7 cells., Methods and Results: To evaluate anti-inflammatory activities of L. reuteri LM1071, LPS-stimulated RAW264.7 cells were used. Gene expression levels of eight immune-associated genes including IL-1β, IL-6 and TNF-α and protein production levels of COX-1 and COX-2 were analysed. Moreover, the production of eicosanoids as important biomarkers for anti-inflammation was determined., Conclusions: The current study demonstrates that L. reuteri LM1071 has anti-inflammatory potential by inhibiting the production of inflammation mediators such as NO, eicosanoids such as PGE1 & PGE2, pro-inflammatory cytokines and COX proteins. It can also enhance the production of inflammatory associated genes such as IL-11, BMP4, LEFTY2 and EET metabolite., Significance and Impact of the Study: Lactobacillus reuteri is one of the crucial bacteria for food fermentation. It can be found in the gastrointestinal system of human and animals. Several studies have shown that L. reuteri has valuable effects on host health. The current study firstly demonstrated that L. reuteri has a beneficial effect on the inflammation containing the variation of eicosanoids (PGE1 and PGE2) which are one of the most important biomarkers and moreover eicosanoid-associated genes as well as proteins (COX-2)., (© 2021 The Society for Applied Microbiology.)

The adaptive CRT (aCRT) is an innovative algorithm that was developed to avoid unnecessary right ventricular (RV) pacing through continuous intracardiac delay evaluation. We present a case of unexpected wide QRS paced rhythm after successful implantation of CRT in patients with right bundle branch block (RBBB) and describe the reasons and the programming changes required to resolve it., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Blood type is reportedly correlated with the occurrence of cardiovascular diseases, presumably because of its effect on thrombogenicity. However, the relationship between blood type and thrombotic complications in atrial fibrillation (AF) remains unclear. This retrospective study analyzed the blood types of 1170 AF patients (mean age, 70 years; 58% men) who were followed up for up to 4 years. Patients with greater than mild mitral stenosis or prosthetic valves were excluded. The cohort included 305 (26%) type O, 413 (35%) type A, 333 (28%) type B, and 119 (10%) type AB patients. The primary endpoint of major adverse cerebrovascular events (MACE) occurred in 52 (4.4%) patients. When longitudinal outcomes were plotted, AB blood type patients had worse prognosis than non-AB blood type patients ( p = 0.039), particularly type O blood patients ( p = 0.049). Multivariate Cox regression analysis revealed that AB blood type was associated with higher MACE rates (adjusted hazard ratio, 2.01; 95% confidence interval, 1.01-4.00; p = 0.048) than non-AB blood types independent of anticoagulation therapy duration or CHA2DS2-VASc score. These indicate that AF patients with AB blood type are at an increased risk of MACE compared to those with non-AB blood type independent of the duration of anticoagulation or the CHA 2 DS 2 -VASc score.

Background: Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era., Methods: Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates., Results: A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180., Conclusions: PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Panax ginseng C. A. Meyer is well known as traditional herbal medicine, and ginseng berries are known to exhibit potential immune-enhancing functions. However, little is known about the in vivo immunomodulatory activity of Korean ginseng berries. In this study, crude Korean ginseng berries polysaccharides (GBP) were isolated and their immunomodulatory activities were investigated using cyclophosphamide (CY)-induced immunosuppressive BALB/c mice. In CY-treated mice, oral administration of GBP (50-500 mg/kg BW) remarkably increased their spleen sizes and spleen indices and activated NK cell activities. GBP also resulted in the proliferation of splenic lymphocytes (coordinating with ConA: plant mitogen which is known to stimulate T-cell or LPS: endotoxin which binds receptor complex in B cells to promote the secretion of pro-inflammatory cytokines) in a dose-dependent manner. In addition, GBP significantly stimulated mRNA expression levels of immune-associated genes including interleukin-1β ( IL-1β ), IL-2 , IL-4 , IL-6 , tumor necrosis factor-α ( TNF-α ), interferon-γ ( IFN-γ ), toll-like receptor 4 ( TLR-4 ), and cyclooxygenase-2 ( COX-2 ) in CY-treated mice. These results indicate that GBP is involved in immune effects against CY-induced immunosuppression. Thus, GBP could be developed as an immunomodulation agent for medicinal or functional food application.

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022. The Korean Society of Cardiology.)

Background: The decision-making factors and long-term clinical outcomes between PCI and CABG in left main (LM) disease are still not well defined in the real world., Methods: We evaluated consecutive patients ( n = 230) with LM disease either treated by PCI ( n = 118) or CABG ( n = 112). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, spontaneous myocardial infarction (MI), stroke, and target vessel revascularization (TVR) for 7 years., Results: In the multivariate-adjusted analysis, the presence of intermediate EuroSCORE II and high SYNTAX scores predisposed to CABG. Isolated LM disease was associated with receiving PCI. The PCI group had a similar rate of MACE (HR adj 0.97, 95% CI [0.48-1.94], p = 0.92) and a lower tendency of hard MACE (HR adj 0.49, 95% CI [0.22-1.07], p = 0.07) compared to the CABG group, mainly due to the balance between a higher rate of TVR (HR adj 9.71, p = 0.02) and a lower rate of stroke (HR adj 0.22, p = 0.09) with the PCI group than in the CABG group., Conclusions: The decision making of treatment strategy was made based on clinical and angiographic factors. The selected patients who received PCI showed similar MACE and trend of a lower rate of composite hard endpoints despite multivariate adjustment.

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5 + (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4 + iOPCs was similar to that of O4 + OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development., (© 2022. The Author(s).)

The association between congestive heart failure (CHF) of the CHA 2 DS 2 -VASc scores and thromboembolic (TE) events in patients with atrial fibrillation (AF) is a topic of debate due to conflicting results. As the importance of diastolic impairment in the occurrence of TE events is increasingly recognized, it is crucial to evaluate the predictive power of CHA 2 DS 2 -VASc scores with C criterion integrating diastolic parameters. We analyzed 4200 Korean nonvalvular AF patients (71 years of age, 59% men) to compare multiple echocardiographic definitions of CHF. Various guideline-suggested echocardiographic parameters for systolic or diastolic impairment, including left ventricular ejection fraction (LVEF) ≤ 40%, the ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus (E/E') ≥ 11, left atrial volume index > 34 mL/m 2 , and many others were tested for C criteria. Multivariate-adjusted Cox regression analysis showed that CHA 2 DS 2 -VASc score was an independent predictor for composite thromboembolic events only when CHF was defined as E/E' ≥ 11 (hazard ratio, 1.26; p = 0.044) but not with other criteria including the original definition (hazard ratio, 1.10; p = 0.359). Our findings suggest that C criterion defined as diastolic impairment, such as E/E' ≥ 11, may improve the predictive value of CHA 2 DS 2 -VASc scores.

The current study evaluated the immune-regulatory potential of lipid extract from Halocynthia aurantium tunic on macrophage cells. The results showed that H. aurantium lipid is composed of primarily SFA (68.32%), followed by MUFA and PUFA (17.61% and 14.07%, respectively). Halocynthia aurantium lipid dose-dependently modulated the NO and PGE 2 production in RAW264.7 cells without any LPS stimulation. The lipid effectively up-regulated the cytokine expression, including IL-1β , IL-6 , and TNF -α in RAW264.7 cells. The COX-2 expression as a key biomarker for inflammation was also significantly increased. Conversely, H. aurantium lipid down-regulated the expression of inflammatory cytokines in LPS-stimulated RAW264.7 cells. Halocynthia aurantium lipid modulated the phosphorylation of NF-κB p-65, p38, ERK, and JNK, indicating that this lipid activated through NF-κB and MAPK pathways. These results provide insight into the immune-regulatory activities of H. aurantium tunic lipid and suggest that H. aurantium tunic may a potential lipid source for immune-regulatory molecules., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2021.)

Biodegradable polymers (BDPs) and ultrathin struts were recently introduced to drug-eluting stents (DES) to further improve outcomes. In this study, we analyzed and compared the effect of the ultrathin strut BDP-DES (UBDP-DES) with the conventional durable polymer-DES (DP-DES) in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI). A total of 356 STEMI patients (n = 160 in the UBDP-DES group and n = 196 in the DP-DES group) were enrolled. The primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction, and ischemic-driven, target lesion revascularization (ID-TLR). The mean age was 60.3 ± 12.7 years (male 81.7%), and the median follow-up duration was 63.8 months. TLF was numerically more frequent in the UBDP-DES group (8.1% vs. 4.1%; HR 2.14; 95% CI 0.89-5.18; p = 0.091). Propensity score matching (PSM) was performed to balance discrepancies in the baseline characteristics due to patients in the UBDP-DES group initially having more unstable vital signs. However, after PSM (n = 116 in each group), there was no significant difference in TLF (5.3% vs. 5.3%; HR 1.04, 95% CI 0.34-3.22; p = 0.947) or other secondary endpoints including ID-TLR. In the subgroup analysis, subjects with initial acute heart failure (AHF), defined as Killip class ≥ 3, were associated with 13.6% chance of 30-day mortality (9-fold of those without AHF), although chances of repeat revascularization were low (3.0%). Among patients with AHF, the UBDP-DES group was associated with a numerically higher chance of TLF compared with the DP-DES group. There was no difference in TLF between groups in patients without AHF. This study showed that UBDP-DES has long-term clinical outcomes similar to those of conventional DP-DES in real-world Korean STEMI patients receiving PPCI, especially in those without initial AHF.

The diagnostic and prognostic role of nitroglycerin-induced dilation (NID) combined with ergonovine provocation test in patients with suspected VSA patients is not clear. A total of 438 consecutive patients who underwent the ergonovine provocation test for the diagnosis of vasospastic angina (VSA) were enrolled. Patients with VSA (n = 52) had a significantly greater coronary response to ergonovine (- 84.3 ± 10.5% vs. - 38.4 ± 17.9%, p < 0.001) and NID (26.3 ± 31.0% vs. 12.5 ± 19.0%, p < 0.001) than non-VSA patients. However, positive NID (more than 13.8% dilation, n = 170) showed a poor accuracy (AUC 0.64 [95% CI: 0.56-0.73], p = 0.001, sensitivity 60.4%, specificity 61.3%) for the diagnosis of VSA by ergonovine provocation test. Major adverse cardiovascular events (MACE) occurred more frequently in the VSA group than in the non-VSA group (9.6% vs. 2.2%, p = 0.006). In addition, the positive NID group showed a lower rate of MACE than the negative NID group (1.2% vs. 4.3%, p = 0.021). Interestingly, the group of VSA with negative NID had poor prognosis than any other combinations (Log-rank, p < 0.0001). Although NID had a limited role in the detection of VSA defined by ergonovine provocation test, NID combined with the ergonovine provocation test has an additive prognostic role in the clinical outcomes in patients with suspected VSA., (© 2021. The Author(s).)

Determination of modifiable factors associated with changes in health perception can be beneficial for improvement in health perception and health-related quality of life. The purpose of this study was to examine if changes in physical symptoms, functional status, and depressive symptoms were associated with changes in health perception at three months and the mediator effect of physical symptoms. Data were collected at baseline and three months later (N = 65). Process Macro for SPSS was used to analyze the data. Only changes in depressive symptoms (p < .001) were associated with changes in physical symptoms. Then, only changes in physical symptoms (p = .026) were significantly associated with changes in health perception. Changes in physical symptoms played significant roles in changes in health perception directly and also through the mediator role. Clinicians and researchers need to assess and manage these two modifiable factors to improve health perception in this population.

We evaluated the angiographic parameter and clinical outcomes of drug-coated balloon (DCB) to assess the optimal angiographic criteria in de novo small vessel disease (SVD). Patients (n = 424, mean age: 64.4 ± 11.2 years, men: 69.8%) at 20 sites in Korea were prospectively enrolled. The primary end point was late luminal loss (LLL) at 9-month follow-up angiography. Secondary end points included restenosis rates, target lesion failure (TLF), and DCB-related thrombosis during the 12-month follow-up period. We included 403 patients for analysis excluding 21 patients who required bailout stenting. Baseline mean reference vessel .diameter was 2.52 ± 0.39 mm and mean minimal luminal diameter (MLD) was 0.71 ± 0.40 mm. The mean MLD was 1.54 ± 0.37 mm after DCB. Late luminal loss was -0.01 ± 0.43 mm and restenosis was noted in 26 patients (12.2%). Minimal luminal diameter >1.6 mm and % diameter stenosis ( DS ) <45% after DCB was associated maintenance of MLD without LLL at 9-months. Multivariate analysis demonstrated that %DS at baseline and post-MLD was associated with the restenosis. During 12-month follow-up, TLF was 2.6% including 1 cardiac death, 1 myocardial infarction, and 10 ischemia-driven target lesion revascularizations. Drug-coated balloon showed a low restenosis and lower LLL despite high in-segment DS. Post-MLD and % DS may be helpful to get optimal results in de novo SVD after DCB.

Ammodytes personatus , known as the Pacific sand lance, thrives in cold areas of the North Pacific. In this study, the total lipid was extracted from A. personatus eggs and the fatty acid composition was determined using gas chromatography (GC)-flame ionization detection (FID). The results showed that the extracted lipid contained high content of polyunsaturated fatty acids (PUFAs). The immunomodulatory activities of the A. personatus lipid were investigated using rodent macrophages. First, immune enhancement was analyzed, and the A. personatus lipid significantly and dose-dependently increased the NO production in RAW264.7 cells, and this lipid also regulated the transcription of immune-associated genes in RAW264.7 cells by activating the NF-κB and MAPK pathways. Additionally, flow cytometry revealed that this lipid stimulated phagocytosis. Conversely, the anti-inflammatory activity of the A. personatus lipid was also analyzed and the results showed significantly decreased NO production and gene expression in a dose-dependent manner in LPS-stimulated RAW264.7 cells. In addition, the A. personatus lipid suppressed the LPS-induced phosphorylation of proteins related to the NF-κB and MAPK pathways in LPS-stimulated RAW264.7 cells. Further, flow cytometry demonstrated the lipid-regulated anti-inflammatory activity via inhibition of CD86 expression. The results indicate that A. personatus egg lipid is a potential source of immunomodulation.

It remains inconclusive whether the additional low-density lipoprotein cholesterol (LDL-C) lowering effects of ezetimibe added to statin on coronary atherosclerosis and clinical outcomes are similar to those of statin monotherapy in the setting of comparable LDL-C reduction. We aimed to determine whether there were distinguishable differences in their effects on coronary atherosclerosis with intermediate stenosis between the combination of moderate-intensity statin plus ezetimibe and high-intensity statin monotherapy. Forty-one patients with stable angina undergoing percutaneous coronary intervention were randomized to receive either atorvastatin 10 mg plus ezetimibe 10 mg (ATO10/EZE10) or atorvastatin 40 mg alone (ATO40). The intermediate lesions were evaluated using a near-infrared spectroscopy-intravascular ultrasonography at baseline and after 12 months in 37 patients. The primary endpoint was percent atheroma volume (PAV). Mean LDL-C levels were significantly reduced by 40% and 38% from baseline in the ATO10/EZE10 group (n = 18, from 107 mg/dL to 61 mg/dL) and ATO40 group (n = 19, from 101 mg/dL to 58 mg/dL), respectively, without between-group difference. The absolute change of PAV was -2.9% in the ATO10/EZE10 group and -3.2% in the ATO40 group. The mean difference (95% confidence interval) for the absolute change in PAV between the 2 groups was 0.5% (-2.4% to 2.8%), which did not exceed the pre-defined non-inferiority margin of 5%. There was no significant reduction in lipid core burden index in both groups. In conclusion, the combination of atorvastatin 10 mg and ezetimibe 10 mg showed comparable LDL-C lowering and regression of coronary atherosclerosis in the intermediate lesions, compared with atorvastatin 40 mg alone., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Streptococcus agalactiae is the leading cause of meningitis in newborns and a significant cause of invasive diseases in pregnant women and adults with underlying diseases. Antibiotic resistance against erythromycin and clindamycin in group B streptococcus (GBS) isolates has been increasing worldwide. GBS expresses the Srr1 and Srr2 proteins, which have important roles in bacterial infection. They have been investigated as novel vaccine candidates against GBS infection, with promising results. But a recent study detected non- srr1/2 -expressing clinical isolates belonging to serotype III. Thus, we aimed to analyze the genotypes of non- srr1/2 GBS clinical isolates collected between 2013 and 2016 in South Korea. Forty-one (13.4%) of the 305 serotype III isolates were identified as non- srr1/2 strains, including sequence type 19 (ST19) ( n  = 16) and ST27 ( n  = 18) strains. The results of the comparative genomic analysis of the ST19/serotype III/non- srr1/2 strains further revealed four unique gene clusters. Site 4 in the srr1 gene locus was replaced by an lsa (E)- lnu (B)- aadK - aac-aph - aadE -carrying multidrug-resistant gene cluster flanked by two IS 1216 transposases with 99% homology to the enterococcal plasmid pKUB3007-1. Despite the Srr1 and Srr2 deficiencies, which resulted in reduced fibrinogen binding, the adherence of non- srr1/2 strains to endothelial and epithelial cells was comparable to that of Srr1- or Srr2-expressing strains. Moreover, their virulence in mouse models of meningitis was not significantly affected. Furthermore, additional adhesin-encoding genes, including a gene encoding a BspA-like protein, which may contribute to colonization by non- srr1/2 strains, were identified via whole-genome analysis. Thus, our study provides important findings that can aid in the development of vaccines and antibiotics against GBS. IMPORTANCE Most previously isolated group B streptococcus (GBS) strains express either the Srr1 or Srr2 glycoprotein, which plays an important role in bacterial colonization and invasion. These glycoproteins are potential protein vaccine candidates. In this study, we first report GBS clinical isolates in which the srr1/2 gene was deleted or replaced with foreign genes. Despite Srr1/2 deficiency, in vitro adherence to mammalian cells and in vivo virulence in murine models were not affected, suggesting that the isolates might have another adherence mechanism that enhanced their virulence aside from Srr1/2-fibrinogen-mediated adherence. In addition, several non- srr1/2 isolates replaced the srr1/2 gene with the lnu (B) and lsa (E) antibiotic resistance genes flanked by IS 1216 , effectively causing multidrug resistance. Collectively, we believe that our study identifies the underlying genes responsible for the pathogenesis of new GBS serotype III. Furthermore, our study emphasizes the need for alternative antibiotics for patients who are allergic to β-lactams and for those who are pregnant.

Dyslipidemia is one of the most important risk factors for cardiovascular (CV) disease. Statin therapy has dramatically improved CV outcomes and is the backbone of current lipid-lowering therapy, but despite well-controlled low-density lipoprotein cholesterol (LDL-C) levels through statin administration, up to 40% patients still experience CV disease. New therapeutic agents to tackle such residual cholesterol risk by lowering not only LDL-C but triglycerides (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp(a)) are being introduced. Ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, PCSK9 small interference RNA (siRNA), and bempedoic acid added to statin therapy have shown additional improvement to CV outcomes. Recent trials administering eicosapentaenoic acid to patients with high TG despite statin therapy have also demonstrated significant CV benefit. Antisense oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now being newly introduced with promising lipid-lowering effects. ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipid profiles without requiring high or frequent doses. Clinical outcomes from these novel therapeutics are yet to be proven. Here, we review current and emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual CV risk.

Streptococcus agalactiae (group B Streptococcus , GBS) is a leading cause of neonatal sepsis and meningitis in infants. Limitations of prenatal GBS screening and intrapartum antibiotic prophylaxis render developing GBS vaccines a high priority. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) for the practical and large-scale evaluation of GBS capsular polysaccharide (PS) vaccine immunogenicity against three main serotypes, Ia, III, and V. GBS-ELISA was developed and subsequently validated using a standardized curve-fitting four-parameter logistic method. Specificity was measured using adsorption of serum with homologous and heterologous PS. Homologous adsorption showed a ≥75% inhibition of all three serotypes, whereas with heterologous PS, IgG GBS-ELISA inhibited only ≤25% of serotypes III and V. However, with serotype Ia, IgG antibody levels decreased by >50%, even after adsorption with heterologous PS (III or V). In comparison, the inhibition opsonophagocytic killing assay (OPA) of serotypes Ia GBS exhibited a reduction in opsonophagocytic activity of only 20% and 1.1% for serotypes III and V GBS, respectively. The precision of the GBS-ELISA was assessed in five independent experiments using four serum samples. The coefficient of variation was <5% for all three serotypes. This standardized GBS-ELISA would be useful for GBS vaccine development and its evaluation.

Purpose: Heart failure (HF) poses significant morbidity and mortality. Recently, the ventriculo-vascular coupling index (VVI) was introduced as an independent prognostic factor reflective of the overall cardiovascular performance index in HF. We aimed to determine the effectiveness of force-titration of valsartan on VVI values in HF patients., Materials and Methods: In this multicenter and prospective observational trial, the effect of valsartan was stratified according to dosages [non-ceiling dose (NCD) vs. ceiling dose (CD)] in HF patients with left ventricular ejection fraction (LVEF) <55%. Biochemical studies, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography with VVI, the treadmill test, and the activity scale index were assessed at baseline and after 24 weeks of treatment., Results: One-hundred thirty-eight patients were force-titrated to either a CD group (n=81) or a NCD group (n=57). The mean age of the study participants was 59 years and 66% were male. After 6 months of follow up, left ventricular mass index (LVMI) values had significantly improved in the CD group but not in the NCD group. Intriguingly, in HF patients with a reduced ejection fraction (HFrEF) (n=52, LVEF <40%), a significant improvement in VVI was only observed in the CD group (from 2.4±0.6 to 1.8±0.5, p <0.001)., Conclusion: CDs of valsartan for 6 months showed better improvement in VVI, as well as LVMI, in patients with HFrEF, compared with NCDs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)