Summary
Background
Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects ...of human umbilical cord blood‐derived MSCs (huMSCs) remain largely unexamined for asthma.
Objective
This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)‐induced murine asthma model.
Methods
Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen‐specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells.
Results
Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA‐specific IgE and IgG1 levels along with Th2 cytokine production (IL‐4, IL‐5, and IL‐13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs.
Conclusions
Our results suggest that huMSC treatment reduces OVA‐induced allergic inflammation, which could be mediated by regulatory T cells.
Objective
The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE).
Methods
Patients from the Hanyang ...BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE.
Results
Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01–1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03–2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24–0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85–1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03–9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12–28.96, p < 0.01).
Conclusion
Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.
Summary Objective To evaluate the interaction of articular cartilage (AC) and subchondral bone (SB) through analysis of osteoarthritis (OA)-related genes of site-matched tissue. Design We developed a ...novel method for isolating site-matched overlying AC and underlying SB from three and four regions of interest respectively from the human knee tibial plateau ( n = 50). For each site, the severity of cartilage changes of OA were assessed histologically, and the severity of bone abnormalities were assessed by microcomputed tomography. An RNA isolation procedure was optimized that yielded high quality RNA from site-matched AC and SB tibial regions. Quantitative polymerase chain reaction (Q-PCR) analysis was performed to evaluate gene expression of 61 OA-associated genes for correlation with cartilage integrity and bone structure parameters. Results A total of 27 (44%) genes were coordinately up- or down-regulated in both tissues. The expression levels of 19 genes were statistically significantly correlated with the severity of AC degeneration and changes of SB structure; these included: ADAMTS1 , ASPN , BMP6 , BMPER , CCL2 , CCL8 , COL5A1 , COL6A3 , COL7A1 , COL16A1 , FRZB , GDF10 , MMP3 , OGN , OMD , POSTN , PTGES , TNFSF11 and WNT1. Conclusions These results provide a strategy for identifying targets whose modification may have the potential to ameliorate pathological alterations and progression of disease in both AC and SB simultaneously. In addition, this is the first study, to our knowledge, to overcome the major difficulties related to isolation of high quality RNA from site-matched joint tissues. We expect this method to facilitate advances in our understanding of the coordinated molecular responses of the whole joint organ.
Background and purpose
We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial ...fibrillation.
Methods
The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.
Results
Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance 103 episodes (31.3%) followed by extracranial bleeding 96 episodes (29.2%). Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2DS2‐VASc score were not significantly different between patients with and without recurrent stroke.
Conclusions
A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
Within the next decade, we will see many gene therapy clinical trials for eye diseases, which may lead to treatments for thousands of visually impaired people around the world. To target retinal ...diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in preclinical mouse studies. Because there are numerous anatomic and physiologic differences between the eyes of mice and "men" and because surgical delivery approaches and immunologic responses also differ between these species, this study evaluated the transduction characteristics of two promising new serotypes, AAV7m8 and AAV8BP2, in the retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, transduction by both serotypes in the anterior chamber of the eye and the optic pathway of the brain was observed post-intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared with AAV7m8, even at the highest doses administered. These studies underscore the differences in AAV transduction between mice and primates, highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving to clinical trials.
Summary Objective To identify disease relevant genes and pathways associated with knee Osteoarthritis (OA) progression in human subjects using medial and lateral compartment dominant OA knee tissue. ...Design Gene expression of knee cartilage was comprehensively assessed for three regions of interest from human medial dominant OA ( n = 10) and non-OA ( n = 6) specimens. Histology and gene expression were compared for the regions with minimal degeneration, moderate degeneration and significant degeneration. Agilent whole-genome microarray was performed and data were analyzed using Agilent GeneSpring GX11.5. Significant differentially regulated genes were further investigated by Ingenuity Pathway Analysis (IPA) to identify functional categories. To confirm their association with disease severity as opposed to site within the knee, 30 differentially expressed genes, identified by microarray, were analyzed by quantitative reverse-transcription polymerase chain reaction on additional medial ( n = 16) and lateral ( n = 10) compartment dominant knee OA samples. Results A total of 767 genes were differentially expressed ≥two-fold ( P ≤ 0.05) in lesion compared to relatively intact regions. Analysis of these data by IPA predicted biological functions related to an imbalance of anabolism and catabolism of cartilage matrix components. Up-regulated expression of IL11, POSTN, TNFAIP6, and down-regulated expression of CHRDL2, MATN4, SPOCK3, VIT, PDE3B were significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples. Conclusions Our study provides a strategy for identifying targets whose modification may have the potential to ameliorate pathological alternations and progression of disease in cartilage and to serve as biomarkers for identifying individuals susceptible to progression.
Background
Statins are widely used in coronary and peripheral arterial disease, but their impact on patency of stents placed for peripheral arterial disease is not well-studied. The purpose of this ...study was to evaluate femoropopliteal stent primary patency according to statin intensity at the time of stent placement and compare this effect to other covariates that may influence stent patency.
Materials and methods
A retrospective review identified 278 discrete femoropopliteal stent constructs placed in 216 patients over a 10-year period; Rutherford categories were 2 (3.6%), 3 (12.9%), 4 (21.2%), 5 (49.6%), and 6 (12.6%). Stent locations were common femoral (1.8%), common femoral/superficial femoral (0.7%), superficial femoral (50.7%), superficial femoral/popliteal (32.7%) and popliteal (14.0%) arteries; 63.3% of stents were paclitaxel-eluting. Primary patency of each stent construct was determined with duplex ultrasound, angiography, or computed tomographic angiography. Greater than 50% restenosis or stent occlusion was considered loss of patency. Cox proportional hazard and Kaplan–Meier modeling were used to assess the effect of statin use and additional covariates on stent patency.
Results
Patients on any statin at the time of stent placement were half as likely to undergo loss of primary unassisted patency as patients on no statin therapy (hazard ratio, 0.53; 95% confidence interval, 0.19–0.87;
P
= .004). Moderate/high intensity statin therapy conferred 17 additional months of median stent patency compared to the no statin group. Antiplatelet therapy, anticoagulant therapy, drug-eluting stents (versus bare metal or covered stents), and Rutherford class were not predictive of stent patency (
P
= 0.52, 0.85, 0.58, and 0.82, respectively).
Conclusion
Use of statin therapy at the time of femoropopliteal stent placement was the most predictive examined variable influencing primary unassisted patency.
We present the effect of geometrical parameters, particularly shape, on optical absorption enhancement for thin film solar cells based on crystalline silicon (c-Si) and gallium arsenide (GaAs) using ...a rigorous coupled wave analysis (RCWA) method. It is discovered that the "sweet spot" that maximizes efficiency of solar cells exists for the design of nanophotonic surfaces. For the case of ultrathin, rod array is practical due to the effective optical resonances resulted from the optimum geometry whereas parabola array is viable for relatively thicker cells owing to the effective graded index profile. A specific value of thickness, which is the median value of other two devices tailored by rod and paraboloid, is optimized by truncated shape structure. It is therefore worth scanning the optimum shape of nanostructures in a given thickness in order to achieve high performance.
A novel genotype of H5N6 influenza viruses was isolated from migratory birds in South Korea during November 2016. Domestic outbreaks of this virus were associated with die-offs of wild birds near ...reported poultry cases in Chungbuk province, central South Korea. Genetic analysis and animal studies demonstrated that the Korean H5N6 viruses are highly pathogenic avian influenza (HPAI) viruses and that these viruses are novel reassortants of at least three different subtypes (H5N6, H4N2 and H1N1).
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