Objective
Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using ...clinical and serological manifestations in SLE patients.
Methods
We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.
Results
Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio HR 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4).
Conclusion
Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known. This study aimed to evaluate the apoptotic action of CBD in ...colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway. CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased. After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner. Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.
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•Our results strongly suggest, for the first time, that CBD can cause Noxa-induced cell death.•CBD induced apoptotic cell death via ROS/Endoplasmic Reticulum stress-regulated Noxa activation in colorectal cancer cells.•These results suggest that CBD has important implications for the potential treatment of human CRC.
Background
Although the optimal use of prescribed medications for stroke survivors is critical for preventing secondary stroke, longitudinal observations of the natural course of medication ...persistence and adherence in Korean stroke survivors are rare. Furthermore, studies are needed to identify strong predictors influencing medication adherence and to determine whether these predictors change over time.
Aims and objectives
To evaluate the longitudinal medication persistence and adherence at 3 months and 1 year after discharge in all stroke patients and to identify predictors of long‐term medication adherence in patients who can self‐medicate.
Design
A multicentre, prospective, longitudinal descriptive study.
Methods
A total of 600 consecutive ischaemic stroke patients were recruited from three stroke centres across Korea, from 1 September, 2017 to 28 February, 2019. Various factors related to medication adherence suggested by the World Health Organisation were investigated through face‐to‐face interviews at each centre during hospitalisation. Medication persistence and adherence were assessed at 3 months and 1 year after discharge using the eight‐item Morisky Medication Adherence Scale through telephone interviews.
Results
Of 537 survivors at 3 months, 526 (98.0%) were persistent and 472 (89.7%) were adherent. Of 493 survivors at 1 year, 477 (96.8%) were persistent and 392 (82.2%) were adherent. Medication belief, income and health literacy were statistically significant predictors of three‐month medication adherence, which predicted one‐year medication adherence with older age and low income.
Conclusions
Among Korean stroke survivors, three‐month and one‐year medication persistence and adherence were relatively good. Medication beliefs and three‐month medication adherence were important and modifiable factors predicting three‐month adherence and one‐year adherence, respectively.
Relevance to clinical practice
To increase long‐term adherence to medication, various strategies are needed to improve beliefs about medication, taking into account the patient's age and level of knowledge. These interventions need to be initiated during hospitalisation to form early medication habits after discharge.
To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.
Using ...a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.
Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412).
Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.
Thermally activated delayed fluorescence (TADF) materials have emerged as an efficient emitter for achieving high efficiency of blue organic light emitting diodes (OLEDs). However, it is challenging ...to satisfy both high device efficiency and long operational lifetime together. Here, highly efficient and electrochemically stable blue TADF emitter, 5‐(5,9‐dioxa‐13b‐boranaphtho3,2,1‐deanthracen‐7‐yl)‐10,15‐diphenyl‐10,15‐dihydro‐5H‐diindolo3,2‐a:3′,2′‐ccarbazole (DBA‐DI) is designed and synthesized for high efficiency and long lifetime OLED. This emitter exhibits high photoluminescence quantum yield of 95.3%, small single‐triplet energy gap of 0.03 eV, short delayed exciton lifetime of 1.25 µs, and high bond dissociation energy (BDE). Also, phosphine oxide free high triplet energy host systems (single and mixed) and exciton blocking layer materials are analyzed using molecular and optical simulations to find an efficient host system with high BDE and suitable emission zone for high efficiency and stable OLEDs. The fabricated OLED with DBA‐DI and high triplet host exhibited a maximum external quantum efficiency (EQE) of 28.1% with blue CIE color coordinates of (0.16, 0.39) and long operational lifetime (LT50) of 329 h at the initial luminance of 1000 cd m−2. Furthermore, the mixed host‐based TADF device showed a slightly lower EQE of 26.4% and almost two times longer lifetime (LT50: 540 h) than the single host device.
This work reports a highly efficient and stable thermally activated delayed fluorescence (TADF) emitter for blue organic light‐emitting diode (OLED). The fabricated TADF‐OLED exhibited both high external quantum efficiency (26.4%) and long device lifetime (540 h at the initial brightness of 1000 cd m−2) together due to the short‐delayed lifetime, small ΔEST, high bond dissociation energy of emitter, and well‐controlled emission zone.
We present a systematic study on the gate length (<inline-formula> <tex-math notation="LaTeX">{L}_{{g}}\text {)} </tex-math></inline-formula> scaling behavior and the impact of the side-recess ...spacing (<inline-formula> <tex-math notation="LaTeX">{L}_{\text {side}}\text {)} </tex-math></inline-formula> on dc and high-frequency characteristics of In0.8Ga0.2As quantum-well (QW) high-electron-mobility transistors (HEMTs) with <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> from 10 <inline-formula> <tex-math notation="LaTeX">\mu </tex-math></inline-formula>m to 20 nm, for the purpose of understanding the scaling limit of maximum oscillation frequency (<inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}}\text {)} </tex-math></inline-formula> and thereby demonstrating terahertz devices. The fabricated In0.8Ga0.2As QW HEMTs with <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} =20 </tex-math></inline-formula> nm and <inline-formula> <tex-math notation="LaTeX">{L}_{\text {side}} =150 </tex-math></inline-formula> nm exhibited values of drain-induced-barrier-lowering (DIBL) of 60 mV/V, current-gain cutoff frequency (<inline-formula> <tex-math notation="LaTeX">{f}_{{T}}\text {)} </tex-math></inline-formula> of 0.75 THz, and <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> of 1.1 THz, while the device with <inline-formula> <tex-math notation="LaTeX">{L}_{\text {side}} =50 </tex-math></inline-formula> nm showed DIBL of 110 mV/V and <inline-formula> <tex-math notation="LaTeX">{f}_{{T}} </tex-math></inline-formula>/<inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> of 0.72/0.53 THz. It was central to strictly control short-channel effects (SCEs) from the perspective of DIBL to maximize the improvement of <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula>, as <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> was scaled down deeply. In an effort to understand the <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> scaling behavior of <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula>, we carried out the small-signal modeling for both types of devices and found that the increase of the intrinsic output conductance (<inline-formula> <tex-math notation="LaTeX">{g}_{\text {oi}}\text {)} </tex-math></inline-formula> played a critical role in determining <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> in short-<inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> HEMTs. On the contrary, the fabricated devices with <inline-formula> <tex-math notation="LaTeX">{L}_{\text {side}} =150 </tex-math></inline-formula> nm exhibited a tight control of SCEs at <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> of 20 nm. As a result, <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> in those devices was boosted to 1.1 THz, and more importantly this high <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> was maintained even as <inline-formula> <tex-math notation="LaTeX">{L}_{{g}} </tex-math></inline-formula> was scaled down to 20 nm. The results in this work represent the best balance of <inline-formula> <tex-math notation="LaTeX">{f}_{{T}} </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> in any transistor technology on any material system, displaying both <inline-formula> <tex-math notation="LaTeX">{f}_{{T}} </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">{f}_{\text {max}} </tex-math></inline-formula> in excess of 700 GHz simultaneously.
Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. ...As a continuous effort, we conducted GWAS in a large Korean RA case-control population.
We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.
We identified six new RA-risk loci (
,
,
,
,
and
) with p
<5×10
and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.
This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
Rosuvastatin attenuates bioprosthetic heart valve calcification Lee, Sak; Kim, Dae-Hyun; Youn, Young-Nam ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
September 2019, 2019-09-00, 20190901, Letnik:
158, Številka:
3
Journal Article
Recenzirano
Odprti dostop
There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of the study was to examine the effects of ...statin treatment on calcification in commercially available bioprosthetic heart valves.
Twenty Sprague–Dawley rats were fed a high-fat diet to induce hypercholesterolemia during 4 weeks. They were randomly divided into 2 groups according to statin intake (control, n = 10: high-fat diet/statin; n = 10: high-fat diet with statin). Four commercially available tissue valve (Magna Perimount, Carpentier-Edwards, Irvine, Calif; Hancock, Medtronic, Minneapolis, Minn; Mitroflow, LivaNova, London, England; and Trifecta, St Jude Medical, St Paul, Minn) cusp samples (total 320) were implanted in rat dorsal subcutis at 4 weeks. After implantation, rosuvastatin was administered daily to the statin group. The cusps were explanted at 12 weeks, and calcium levels were determined by atomic absorption spectroscopy. Western blotting, histologic, and immunohistochemical analyses were conducted to identify the anticalcification mechanism of the statin.
The mean calcium level in the control group was significantly higher than in the statin group (P < .01) for all tissue valves (Magna Perimount: 2.67 ± 0.26 mg/g vs 1.31 ± 0.40 mg/g; Hancock: 2.70 ± 0.57 mg/g vs 1.53 ± 0.34 mg/g; Mitroflow: 2.39 ± 0.71 mg/g vs 1.26 ± 0.38 mg/g; Trifecta: 2.54 ± 0.42 mg/g vs 1.63 ± 0.72 mg/g). Inflammatory cell infiltration and interleukin-6 and bone morphogenetic protein 2 expressions were significantly reduced in the statin group.
Statin treatment significantly attenuated bioprosthetic heart valve calcification associated with decreasing the levels of interleukin-6 and bone morphogenetic protein 2. Thus, statin treatment might be helpful for the longevity of bioprosthetic heart valves.
Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The ...purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.
We present a fully analytical model and physical investigation on the source resistance (RS) in InxGa1−xAs quantum-well high-electron mobility transistors based on a three-layer TLM system. The RS ...model in this work was derived by solving the coupled quadratic differential equations for each current component with appropriate boundary conditions, requiring only six physical and geometrical parameters, including ohmic contact resistivity (ρc), barrier tunneling resistivity (ρbarrier), sheet resistances of the cap and channel regions (Rsh_cap and Rsh_ch), side-recessed length (Lside) and gate-to-source length (Lgs). To extract each model parameter, we fabricated two different TLM structures, such as cap-TLM and recessed-TLM. The developed RS model in this work was in excellent agreement with the RS values measured from the two TLM devices and previously reported short-Lg HEMT devices. The findings in this work revealed that barrier tunneling resistivity already played a critical role in reducing the value of RS in state-of-the-art HEMTs. Unless the barrier tunneling resistivity is reduced considerably, innovative engineering on the ohmic contact characteristics and gate-to-source spacing would only marginally improve the device performance.
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