Mesenchymal stem cell (MSC) is a promising tool for the therapy of immune disorders. However, their efficacy and mechanisms in treating allergic skin disorders are less verified. We sought to ...investigate the therapeutic efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) against murine atopic dermatitis (AD) and to explore distinct mechanisms that regulate their efficacy. AD was induced in mice by the topical application of Dermatophagoides farinae. Naïve or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. The subcutaneous administration of nucleotide-binding oligomerization domain 2 (NOD2)-activated hUCB-MSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). A β-hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation. NOD2-activated MSCs reduced the MC degranulation via NOD2-cyclooxygenase-2 signaling. In contrast to bone marrow-derived MSCs, hUCB-MSCs exerted a cell-to-cell contact-independent suppressive effect on MC degranulation through the higher production of prostaglandin E2 (PGE2 ). Additionally, transforming growth factor (TGF)-β1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating FcεRI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE2 and TGF-β1 are required for the inhibition of MC degranulation.
Scope
Intestinal dysbiosis has been reported to play an important role in the pathogenesis of various diseases, including chronic kidney disease (CKD). Here, to evaluate whether probiotic supplements ...can have protective effects against kidney injury in an animal model of CKD is aimed.
Methods and results
An animal model of CKD is established by feeding C57BL/6 mice a diet containing 0.2% adenine. These model mice are administered Lactobacillus acidophilus KBL409 daily for 4 weeks. Features of adenine‐induce CKD (Ade‐CKD) mice, such as prominent kidney fibrosis and higher levels of serum creatinine and albuminuria are improved by administration of KBL409. Ade‐CKD mice also exhibit a disrupted intestinal barrier and elevate levels of TNF‐α, IL‐6, and 8‐hydroxy‐2′‐deoxyguanosine. These changes are attenuated by KBL409. Administration of KBL409 significantly reduces macrophage infiltration and promotes a switch to the M2 macrophage phenotype and increasing regulatory T cells. Notably, the NLRP3 inflammasome pathway is activated in the kidneys of Ade‐CKD and decreases by KBL409. In primary kidney tubular epithelial cells treated with p‐cresyl sulfate, short‐chain fatty acids significantly increase M2 macrophage polarization factors and decrease profibrotic markers.
Conclusions
These results demonstrate that supplementation with the probiotic KBL409 has beneficial immunomodulating effects and protects against kidney injury.
Intestinal dysbiosis plays a significant role in the pathogenesis of chronic kidney disease. Supplementation of Lactobacillus acidophilus KBL409 ameliorates kidney function and fibrosis in adenine‐induced mice model of chronic kidney disease. This effect is mediated by restoration of intestinal barrier, modulation of systemic and renal inflammation, and increased production of short‐chain fatty acids. Therefore, KBL409 can be a potential therapeutic option to prevent progression of chronic kidney disease.
Fiber electronics is a key research area for realizing wearable microelectronic devices. Significant progress has been made in recent years in developing the geometry and composition of electronic ...fibers. In this review, we present that recent progress in the architecture and electrical properties of electronic fibers, including their fabrication methods. We intensively investigate the structural designs of fiber-shaped devices: coaxial, twisted, three-dimensional layer-by-layer, and woven structures. In addition, we introduce remarkable applications of fiber-shaped devices for energy harvesting/storage, sensing, and light-emitting devices. Electronic fibers offer high potential for use in next-generation electronics, such as electronic textiles and smart integrated textile systems, which require excellent deformability and high operational reliability.
Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body ...fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued.
To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach.
Information on compounds in herbal medicines was obtained from public databases, and oral bioavailability and drug-likeness was screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Correlations between compounds and genes were linked using the STITCH database, and genes related to hyperlipidaemia and atherosclerosis were gathered using the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
Network analysis identified 447 compounds in five herbal medicines that were subjected to ADME screening, and 21 compounds and 57 genes formed the main pathways linked to hyperlipidaemia and atherosclerosis. Among them, 10 compounds (naringenin, nobiletin, hesperidin, galangin, glycyrrhizin, homogentisic acid, stigmasterol, 6-gingerol, quercetin and glabridin) were linked to more than four genes, and are bioactive compounds and key chemicals. Core genes in this network were CASP3, CYP1A1, CYP1A2, MMP2 and MMP9. The compound-target gene network revealed close interactions between multiple components and multiple targets, and facilitates a better understanding of the potential therapeutic effects of YJT.
Pharmacological network analysis can help to explain the potential effects of YJT for treating dampness phlegm-related diseases such as hyperlipidaemia and atherosclerosis.
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Subcutaneous adipose tissue (SAT), a vital energy reservoir and endocrine organ for maintaining systemic glucose, lipid, and energy homeostasis, undergoes significant changes with age. However, among ...the existing aging‐related markers, only few genes are associated with SAT aging. In this study, weighted gene co‐expression network analysis was used on a transcriptome of SAT obtained from the Genotype‐Tissue Expression portal to identify biologically relevant, SAT‐specific, and age‐related marker genes. We found modules that exhibited significant changes with age and identified GYG2 as a novel key aging associated gene. The link between GYG2 and mitochondrial function as well as brown/beige adipocytes was supported using additional bioinformatics and experimental analyses. Additionally, we identified PPARG as the transcription factor of GYG2 expression. The newly discovered GYG2 marker can be used to not only determine the age of SAT but also uncover new mechanisms underlying SAT aging.
An analysis of human subcutaneous adipose tissue, using WGCNA, revealed that glycogenin‐2 (GYG2) decreases with age, especially in females. The expression of GYG2 was found to be closely associated with biological age and adipocyte browning.
Ultrathin conformable artificial synapse platforms that can be used as on-body or wearable chips suggest a path to build next-generation, wearable, intelligent electronic systems that can mimic the ...synaptic operations of the human brain. So far, an artificial synapse architecture with ultimate mechanical flexibility in a freestanding form while maintaining its functionalities with high stability and accuracy on any conformable substrate has not been demonstrated yet. Here, we demonstrate the first ultrathin artificial synapse (∼500 nm total thickness) that features freestanding ferroelectric organic neuromorphic transistors (FONTs), which can stand alone without a substrate or an encapsulation layer. Our simple dry peel-off process allows integration of the freestanding FONTs with an extremely thin film that is transferable to various conformable substrates. The FONTs exhibit excellent and reliable synaptic functions, which can be modulated by diverse electrical stimuli and relative timing (or temporal order) between the pre- and postsynaptic spikes. Furthermore, the FONTs show sustainable synaptic plasticity even under folded condition (R = 50 μm, ε = 0.48%) for more than 6000 input spikes. Our study suggests that the ultrathin conformable organic artificial synapse platforms are considered as one of key technologies for realization of wearable intelligent electronics in the future.
Rheumatoid arthritis (RA) is a long-lasting intractable autoimmune disorder, which has become a substantial public health problem. Despite widespread use of biologic drugs, there have been ...uncertainties in efficacy and long-term safety. Mesenchymal stem cells (MSCs) have been suggested as a promising alternative for the treatment of RA because of their immunomodulatory properties. However, the precise mechanisms of MSCs on RA-related immune cells are not fully elucidated. The aim of this study was to investigate the therapeutic potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) as a new therapeutic strategy for patients with RA and to explore the mechanisms underlying hUCB-MSC-mediated immunomodulation. Mice with collagen-induced arthritis (CIA) were administered with hUCB-MSCs after the onset of disease, and therapeutic efficacy was assessed. Systemic delivery of hUCB-MSCs significantly ameliorated the severity of CIA to a similar extent observed in the etanercept-treated group. hUCB-MSCs exerted this therapeutic effect by regulating macrophage function. To verify the regulatory effects of hUCB-MSCs on macrophages, macrophages were co-cultured with hUCB-MSCs. The tumor necrosis factor (TNF)-α-mediated activation of cyclooxygenase-2 and TNF-stimulated gene/protein 6 in hUCB-MSCs polarized naive macrophages toward an M2 phenotype. In addition, hUCB-MSCs down-regulated the activation of nucleotide-binding domain and leucine-rich repeat pyrin 3 inflammasome via a paracrine loop of interleukin-1β signaling. These immune-balancing effects of hUCB-MSCs were reproducible in co-culture experiments using peripheral blood mononuclear cells from patients with active RA. hUCB-MSCs can simultaneously regulate multiple cytokine pathways in response to pro-inflammatory cytokines elevated in RA microenvironment, suggesting that treatment with hUCB-MSCs could be an attractive candidate for patients with treatment-refractory RA.
We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI).
The ...best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear.
Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching.
In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82-0.92) and 0.82 (95% confidence interval: 0.74-0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05).
Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.
Electronic fibres have been considered one of the desired device platforms due to their dimensional compatibility with fabrics by weaving with yarns. However, a precise connecting process between ...each electronic fibre is essential to configure the desired electronic circuits or systems. Here, we present an integrated electronic fibre platform by fabricating electronic devices onto a one-dimensional microfibre substrate. Electronic components such as transistors, inverters, ring oscillators, and thermocouples are integrated together onto the outer surface of a fibre substrate with precise semiconductor and electrode patterns. Our results show that electronic components can be integrated on a single fibre with reliable operation. We evaluate the electronic properties of the chip on the fibre as a multifunctional electronic textile platform by testing their switching and data processing, as well as sensing or transducing units for detecting optical/thermal signals. The demonstration of the electronic fibre suggests significant proof of concepts for the realization of high performance with wearable electronic textile systems.
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