Recently, atopic dermatitis has been suggested as a systemic inflammatory disorder that can accompany other inflammatory diseases, including inflammatory bowel disease. However, comprehensive reviews ...that specifically focus on the association between inflammatory bowel disease and atopic dermatitis are lacking.
To determine the association between inflammatory bowel disease and atopic dermatitis.
We searched for relevant studies from MEDLINE, EMBASE, and the Cochrane Library from inception to November 22, 2019. Considering a potential bidirectional relationship, studies reporting inflammatory bowel disease in patients with atopic dermatitis and atopic dermatitis in patients with inflammatory bowel disease were evaluated separately.
We included 10 studies with 95,291,110 patients (4 studies on the prevalence of atopic dermatitis in inflammatory bowel disease, 2 on the prevalence and incidence of inflammatory bowel disease in atopic dermatitis, and 4 on either the prevalence or incidence of inflammatory bowel disease in atopic dermatitis). Meta-analyses revealed a statistically significant association between inflammatory bowel disease and atopic dermatitis in both directions (4 studies on atopic dermatitis prevalence in inflammatory bowel disease, odds ratio 1.39, 95% confidence interval 1.28-1.50; 5 on inflammatory bowel disease prevalence in atopic dermatitis, odds ratio 1.35, 95% confidence interval 1.05-1.73; and 3 studies on inflammatory bowel disease incidence in atopic dermatitis, relative risk 1.46, 95% confidence interval 0.98-2.17).
A small number of observational studies were reviewed.
Published literature suggests a bidirectional relationship between inflammatory bowel disease and atopic dermatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from ...severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy.
The functional peptide, consisted of anti-PD-L1 peptide and cathepsin B-specific cleavable peptide, is conjugated to a doxorubicin (DOX), resulting in prodrug nanoparticles of PD-NPs
intermolecular interactions. The antitumor efficacy and immune responses with minimal side effects by PD-NPs combining PD-L1 blockade and ICD are evaluated in breast tumor models.
: The PD-NPs are taken up by PD-L1 receptor-mediated endocytosis and then induce ICD in cancer cells by DOX release. Concurrently, PD-L1 blockade by PD-NPs disrupt the immune-suppressing pathway of cancer cells, resulting in proliferation and reinvigoration of T lymphocytes. In tumor models, PD-NPs accumulate within tumor tissues
enhanced permeability and retention (EPR) effect and induce immune-responsive tumors by recruiting a large amount of immune cells.
Collectively, targeted tumor delivery of anti-PD-L1 peptide and DOX
PD-NPs efficiently inhibit tumor progression with minimal side effects.
The histone variant, macroH2A (mH2A) influences gene expression through epigenetic regulation. Tumor suppressive function of mH2A isoforms has been reported in various cancer types, but few studies ...have investigated the functional role of mH2A2 in breast cancer pathophysiology. This study aimed to determine the significance of mH2A2 in breast cancer development and progression by exploring its downstream regulatory mechanisms. Knockdown of mH2A2 facilitated the migration and invasion of breast cancer cells, whereas its overexpression exhibited the opposite effect. In vivo experiments revealed that augmenting mH2A2 expression reduced tumor growth and lung metastasis. Microarray analysis showed that TM4SF1 emerged as a likely target linked to mH2A2 owing to its significant suppression in breast cancer cell lines where mH2A2 was overexpressed among the genes that exhibited over twofold upregulation upon mH2A2 knockdown. Suppressing TM4SF1 reduced the migration, invasion, tumor growth, and metastasis of breast cancer cells in vitro and in vivo. TM4SF1 depletion reversed the increased aggressiveness triggered by mH2A2 knockdown, suggesting a close interplay between mH2A2 and TM4SF1. Our findings also highlight the role of the mH2A2/TM4SF1 axis in activating the AKT/NF‐κB pathway. Consequently, activated NF‐κB signaling leads to increased expression and secretion of MMP13, a potent promoter of metastasis. In summary, we propose that the orchestrated regulation of the mH2A2/TM4SF1 axis in conjunction with the AKT/NF‐κB pathway and the subsequent elevation in MMP13 expression constitute pivotal factors governing the malignancy of breast cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Intestinal fibrosis induced by chronic and recurrent colitis, which is exacerbated by bowel stenosis, stricture, and obstruction, is challenging to treat. Toll-like receptor 4 (TLR4) stimulates ...innate and acquired immunity in response to specific microbial components, but the role of TLR4 in intestinal fibrosis is largely unknown. We investigated its role in intestinal fibrosis using not only a murine fibrosis model but also human myofibroblasts and intestinal epithelial cells. Colon fibrosis was induced in TLR4-deficient (TLR4
) mice and its wild-type counterparts with 3% dextran sulfate sodium. Absence of TLR4 gene attenuated chronic inflammation and colonic macrophages infiltration; intestinal fibrosis and collagen deposition were suppressed. Also, the production of tumor necrosis factor-α, interleukin-12p40, and transforming growth factor-β was reduced in TLR4-deficient peritoneal macrophages. TLR4 was silenced in CCD-18Co cells by small interfering RNA (siRNA), and matrix metalloproteinase-1, tissue inhibitor of metalloproteinase, and collagen α1 expression was evaluated. Role of TLR4 in epithelial-mesenchymal transition (EMT) was evaluated in HCT116 cells. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Recent advent of endovascular thrombectomy (EVT) enables us to provide a new perspective on the use of tPA (tissue-type plasminogen activator) through histological analysis of ...retrieved thrombus. We investigated the responsiveness of intravenous thrombolysis (IVT) according to the thrombus composition in EVT-attempted patients with acute ischemic stroke.
METHODS—We reviewed 92 consecutive patients with anterior circulation stroke who received combined IVT and EVT for 2 years. IVT responsiveness is defined as any decrease in the clot burden from baseline computed tomographic angiography to digital subtraction angiography during EVT. We histologically analyzed the relative fractions of red blood cells (RBCs), congregated fibrin and platelets, and white blood cells in the retrieved thrombi using semiautomated color-based segmentation method. Clinical characteristics according to the RBC fraction were investigated, and associated factors with IVT responsiveness were explored.
RESULTS—Fifty-two patients with histological analyses were stratified into lowest, middle, and highest tertiles of RBC fraction. Toward higher RBC fraction, there was more common susceptibility vessel signs on magnetic resonance imaging (50.0% versus 66.7% versus 91.7%; P=0.022) and prevalent IVT responsiveness (25.0% versus 41.7% versus 75.0%; P=0.010). IVT-responsive group (n=23) had higher RBC fraction (45.7±15.5% versus 35.9±12.2%; P=0.010), lower fibrin and platelet (50.4±14.0% versus 58.5±11.1%; P=0.027), and lower white blood cells fraction (3.9±2.1% versus 5.5±3.0%; P=0.027) than IVT-unresponsive group (n=29). After adjusting for potential variables, RBC fraction (odds ratio, 1.05; 95% confidence interval, 1.01–1.10) remained only independent determinant of IVT responsiveness.
CONCLUSIONS—In EVT-attempted patients with acute ischemic stroke, IVT responsiveness would be closely associated with RBC fraction.
Abstract
Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we ...proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology ...and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex‐matched non‐IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD‐specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non‐IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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