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4,000 |
Erratum: Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder
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4,001 |
Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital
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PURPOSE: To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. PATIENTS AND METHOD: A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. RESULTS: Twenty-five patients with a mean age of 63.2 years (38–92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6–120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). CONCLUSION: Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered.
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4,002 |
Author Correction: Antiviral agents: Targeting vesicle size
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4,003 |
RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells
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Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin’s cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin’s anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.
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4,004 |
Correction: LCE: an open web portal to explore gene expression and clinical associations in lung cancer
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4,005 |
Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway
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Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2(+/−)) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1β elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.
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4,006 |
Outcome measures in juvenile X-linked retinoschisis: A systematic review
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X-linked retinoschisis (XLRS) is a leading cause of hereditary juvenile macular degeneration in males resulting in significant vision impairment. Outcome measures to monitor disease progression or therapeutic interventions have evolved with technology. A systematic review was undertaken to evaluate outcome measures for XLRS. Inclusion criteria were all publications examining outcome measures for natural history studies or following an interventional approach for patients with XLRS. Studies which did not present follow-up data were excluded. We searched medical databases including CENTRAL, Ovid Medline, pre-Medline and ahead of Print up to February 2019. Two authors independently assessed the risk of bias. Twelve studies meet the inclusion criteria with four prospective and eight retrospective case series. Five series were natural history observational studies and seven were interventional series using either topical or systemic carbonic anhydrase inhibitors. Visual acuity (VA) declined very slowly in the natural history studies equivalent to 0.22–0.5 letters per year. Five of the six interventional studies showed an improvement in VA and four a reduction in spectral domain optical coherence tomography (SD-OCT) parameters for central macular thickness (CMT). The full-field electroretinogram identified the 30-Hz latency as a further parameter to monitor function. VA was the measure most likely to show a statistically significant outcome. How functionally meaningful this is, requires further evaluation. CMT SD-OCT outcomes are variable depending on cystic changes. More refined measures are required to better correlate structure with function.
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4,007 |
Advanced robotic surgical systems in ophthalmology
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In this paper, an overview of advanced robotic surgical systems in ophthalmology is provided. The systems are introduced as representative examples of the degree of human vs. robotic control during surgical procedures. The details are presented on each system and the latest advancements of each are described. Future potential applications for surgical robotics in ophthalmology are discussed in detail, with representative examples provided alongside recent progress.
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4,008 |
Antibodies clamp down on NET nucleosomes
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4,009 |
Forced solar gazing—a common technique of torture?
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BACKGROUND: Forced solar gazing (FSG) appears to be more regularly employed as a method of torture in certain parts of the world than has previously been documented. SUBJECTS AND METHODS: This study is a retrospective analysis of a case set of 17 torture survivors subjected to FSG, who were seen by the UK Charity Freedom from Torture in the period 2009–2019. RESULTS: All clients in our case set had experienced serious physical and sexual assaults, in addition to the FSG, as part of their mistreatment. All clients suffered with serious psychological conditions as a result of their torture, including depression and post-traumatic stress disorder (PTSD). These mental health conditions made ophthalmic assessment difficult, not simply because of the clients’ associated anxiety, but also because of avoidant behaviour and dissociation which was manifested in the clinical setting. In the two clients who could be examined by an ophthalmologist, both had visible retinal changes and a degree of impairment of visual acuity. CONCLUSION: FSG appears to be a method of torture which is regularly employed, and in our case set is seen with other serious manifestations of mistreatment, both physical, psychological and sexual. Psychiatric comorbidities present challenges in the clinical assessment of these cases. Ophthalmic examination can carry a risk of re-traumatisation of individuals who have experienced FSG in a context of torture.
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4,010 |
Author Correction: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells
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4,011 |
Management of nystagmus in children: a review of the literature and current practice in UK specialist services
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Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management.
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4,012 |
EMQN best practice guidelines for genetic testing in dystrophinopathies
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Dystrophinopathies are X-linked diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy, due to DMD gene variants. In recent years, the application of new genetic technologies and the availability of new personalised drugs have influenced diagnostic genetic testing for dystrophinopathies. Therefore, these European best practice guidelines for genetic testing in dystrophinopathies have been produced to update previous guidelines published in 2010. These guidelines summarise current recommended technologies and methodologies for analysis of the DMD gene, including testing for deletions and duplications of one or more exons, small variant detection and RNA analysis. Genetic testing strategies for diagnosis, carrier testing and prenatal diagnosis (including non-invasive prenatal diagnosis) are then outlined. Guidelines for sequence variant annotation and interpretation are provided, followed by recommendations for reporting results of all categories of testing. Finally, atypical findings (such as non-contiguous deletions and dual DMD variants), implications for personalised medicine and clinical trials and incidental findings (identification of DMD gene variants in patients where a clinical diagnosis of dystrophinopathy has not been considered or suspected) are discussed.
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4,013 |
Erratum: Modeling psychiatric disorders: from genomic findings to cellular phenotypes
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4,014 |
Opacified hydrophilic intraocular lens following DMEK
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4,015 |
Chromatin accessibility analysis reveals that TFAP2A promotes angiogenesis in acquired resistance to anlotinib in lung cancer cells
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Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Compared with the parental cells, we identified 2666 genomic regions with greater accessibility in anlotinib-resistant cells, in which angiogenesis-related processes and the motifs of 21 transcription factors were enriched. Among these transcription factors, TFAP2A was upregulated. TFAP2A knockdown robustly diminished tumor-induced angiogenesis and partially rescued the anti-angiogenic activity of anlotinib. Furthermore, transcriptome analysis indicated that 2280 genes were downregulated in anlotinib-resistant cells with TFAP2A knocked down, among which the PDGFR, TGF-β, and VEGFR signaling pathways were enriched. Meanwhile, we demonstrated that TFAP2A binds to accessible sites within BMP4 and HSPG2. Collectively, this study suggests that TFAP2A accelerates anlotinib resistance by promoting tumor-induced angiogenesis.
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4,016 |
Phase separation as a therapeutic target in tight junction-associated human diseases
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Tight junctions (TJs) play an important role in the maintenance of epithelial and endothelial barriers. Zonula occludens (ZO) proteins are scaffolding molecules essential for the formation of TJ complexes, and abnormalities in ZO proteins have been implicated in various TJ-associated human diseases such as tumor invasion and metastasis, and barrier dysfunction. Recent studies reveal that liquid–liquid phase separation of ZO proteins drives the polymerization of TJ proteins into a continuous belt, which then recruits various proteins to form the TJ complex to regulate selective paracellular permeability and signal transduction. Herein, we describe recent advances on how ZO phase separation contributes to TJ formation and discuss the potential of phase separation as a target for the treatment of TJ-associated diseases.
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4,017 |
Genome and sequence determinants governing the expression of horizontally acquired DNA in bacteria
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While horizontal gene transfer is prevalent across the biosphere, the regulatory features that enable expression and functionalization of foreign DNA remain poorly understood. Here, we combine high-throughput promoter activity measurements and large-scale genomic analysis of regulatory regions to investigate the cross-compatibility of regulatory elements (REs) in bacteria. Functional characterization of thousands of natural REs in three distinct bacterial species revealed distinct expression patterns according to RE and recipient phylogeny. Host capacity to activate foreign promoters was proportional to their genomic GC content, while many low GC regulatory elements were both broadly active and had more transcription start sites across hosts. The difference in expression capabilities could be explained by the influence of the host GC content on the stringency of the AT-rich canonical σ70 motif necessary for transcription initiation. We further confirm the generalizability of this model and find widespread GC content adaptation of the σ70 motif in a set of 1,545 genomes from all major bacterial phyla. Our analysis identifies a key mechanism by which the strength of the AT-rich σ70 motif relative to a host’s genomic GC content governs the capacity for expression of acquired DNA. These findings shed light on regulatory adaptation in the context of evolving genomic composition.
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4,018 |
Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis
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4,019 |
Publisher Correction: IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure
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4,020 |
Correction: DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes
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4,021 |
Correction: Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway
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4,022 |
Correction: Association of anxiety with subcortical amyloidosis in cognitively normal older adults
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4,023 |
Correction to: Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells
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4,024 |
CMIP is a negative regulator of T cell signaling
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Upon their interaction with cognate antigen, T cells integrate different extracellular and intracellular signals involving basal and induced protein–protein interactions, as well as the binding of proteins to lipids, which can lead to either cell activation or inhibition. Here, we show that the selective T cell expression of CMIP, a new adapter protein, by targeted transgenesis drives T cells toward a naïve phenotype. We found that CMIP inhibits activation of the Src kinases Fyn and Lck after CD3/CD28 costimulation and the subsequent localization of Fyn and Lck to LRs. Video microscopy analysis showed that CMIP blocks the recruitment of LAT and the lipid raft marker cholera toxin B at the site of TCR engagement. Proteomic analysis identified several protein clusters differentially modulated by CMIP and, notably, Cofilin-1, which is inactivated in CMIP-expressing T cells. Moreover, transgenic T cells exhibited the downregulation of GM3 synthase, a key enzyme involved in the biosynthesis of gangliosides. These results suggest that CMIP negatively impacts proximal signaling and cytoskeletal rearrangement and defines a new mechanism for the negative regulation of T cells that could be a therapeutic target.
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4,025 |
Erratum to: Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution
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4,026 |
Taking the scenic route: an endogenous gut lipid messenger curbs binge eating in rats: A research highlight on ‘Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder’ by Romano et al., 2020
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4,027 |
Correction: Epistasis between Pax6(Sey) and genetic background reinforces the value of defined hybrid mouse models for therapeutic trials
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4,028 |
Retraction Note to: Radiographic characteristics that delineate abusive from accidental skull fractures, including the significance of fracture extension to sutures
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4,029 |
Erratum: Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis
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4,030 |
Correction: Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)
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4,031 |
Correction: Extra-mitochondrial citrate synthase initiates calcium oscillation and suppresses age-dependent sperm dysfunction
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4,032 |
Epigenetics in modulating immune functions of stromal and immune cells in the tumor microenvironment
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Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with cancer immunotherapy has been tested both in preclinical settings and in multiple clinical trials. In this review, we highlight the basic biological mechanisms underlying the synergy between epigenetic therapy and immunotherapy and discuss current efforts to translate this knowledge into clinical benefits for patients.
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4,033 |
Cancer immunotherapy with γδ T cells: many paths ahead of us
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γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.
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4,034 |
Correction: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia
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4,035 |
Correction: Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
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4,036 |
Correction: Corrigendum: Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
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4,037 |
Erratum zu: Händehygiene in Einrichtungen des Gesundheitswesens: Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut
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4,038 |
Correction to: Restoring the unrestorable! Developing coronal tooth tissue with a minimally invasive surgical extrusion technique
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4,039 |
Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes
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Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years.
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4,040 |
Retraction Note: Selected TLR7/8 agonist and type I interferon (IFN‑α) cooperatively redefine the microglia transcriptome
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4,041 |
Correction: Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer
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4,042 |
Erratum: Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival
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4,043 |
Expanding cultural and ancestral representation in psychiatric genetic studies
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4,044 |
Correction to: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance
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4,045 |
Meibomian gland dysfunction, dropout and distress: emerging therapies
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4,046 |
Erratum
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4,047 |
Correction: S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells
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4,048 |
Publisher Correction: Ecological and evolutionary approaches to managing honeybee disease
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4,049 |
Erratum to: Inhibitory effects of bee venom and its components against viruses in vitro and in vivo
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4,050 |
Drug development in targeting ion channels for brain edema
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Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial pressure and compromising perfusion. Mortality due to cerebral edema is high. With mortality rates up to 80% in severe cases of stroke, it is the leading cause of death within the first week. Similarly, cerebral edema is devastating for patients of TBI, accounting for up to 50% mortality. Currently, the available treatments for cerebral edema include hypothermia, osmotherapy, and surgery. However, these treatments only address the symptoms and often elicit adverse side effects, potentially in part due to non-specificity. There is an urgent need to identify effective pharmacological treatments for cerebral edema. Currently, ion channels represent the third-largest target class for drug development, but their roles in cerebral edema remain ill-defined. The present review aims to provide an overview of the proposed roles of ion channels and transporters (including aquaporins, SUR1-TRPM4, chloride channels, glucose transporters, and proton-sensitive channels) in mediating cerebral edema in acute ischemic stroke and TBI. We also focus on the pharmacological inhibitors for each target and potential therapeutic strategies that may be further pursued for the treatment of cerebral edema.
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4,051 |
Attitudes of relatives of mucopolysaccharidosis type III patients toward preconception expanded carrier screening
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Preconception expanded carrier screening (ECS) aims to detect carrier couples of autosomal recessive (AR) disorders before pregnancy in order to increase reproductive autonomy of prospective parents. Genetic knowledge and knowledge gained from experience influence decision making on participation in genetic testing and understanding carrier test results. In this study we assessed whether parents and relatives of patients with the severe AR condition mucopolysaccharidosis type III (MPS III), who are expected to have genetic and experiential knowledge, have more positive attitudes toward ECS than the Dutch reference group. Parents of all MPS III patients known to the Dutch expert center were invited to participate and asked to invite first and second degree relatives. The online questionnaire started with an educational text, and assessed attitudes toward ECS, genetic knowledge and perceived MPS III severity. Results were compared with the Dutch population. Parents and relatives of MPS III patients (n = 159) scored higher on the genetic knowledge test and perceived MPS III as more severe compared with the general Dutch population (n = 781). Parents and relatives reported to be more likely to participate in ECS (84.3% and 62.5%, respectively) compared with the public (31%) (p < 0.001). Being a relative of a MPS III patient was the strongest variable in the regression analyses for intended ECS participation. Our results show that genetic knowledge influences ECS decision making. Therefore, appropriate information on ECS and genetic counseling is needed to enable prospective parents from the general population, including relatives of patients with severe hereditary disorders, to make informed decisions.
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4,052 |
Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex
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Leukocyte immunoglobulin (Ig)-like receptors (LILRs), also known as CD85 and immunoglobulin-like transcripts (ILTs), play pivotal roles in regulating immune responses. These receptors define an immune checkpoint that immune therapy can target. Through cis or trans interactions with human leukocyte antigen (HLA)-G, the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy and transplantation, autoimmune diseases, and immune evasion by tumors. Although the discrete domains of LILRB1/2 are clear, the assembly mode of the four extracellular Ig-like domains (D1, D2, D3, and D4) remains unknown. Previous data indicate that D1D2 is responsible for binding to HLA class I (HLA-I), but the roles of D3D4 are still unclear. Here, we determined the crystal structure of the four Ig-like domain LILRB2 and four-domain LILRB1 in complex with HLA-G1. The angles between adjacent domains and the staggered assembly of the four domains suggest limited flexibility and limited plasticity of the receptors during ligand binding. The complex structure of four-domain LILRB1 and HLA-G1 supports the model that D1D2 is responsible for HLA-I binding, while D3D4 acts as a scaffold. Accordingly, cis and trans binding models for HLA-I binding to LILRB1/2 are proposed. The geometries of LILRB1/2 in complex with dimeric and monomeric HLA-G1 suggest the accessibility of the dimeric receptor, which in turn, transduces more inhibitory signals. The assembly of LILRB1/2 and its binding to HLA-G1 could aid in the design of immune regulators and benefit immune interference.
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4,053 |
Omission of previous publications by an author should be corrected
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4,054 |
The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals
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Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.
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4,055 |
Erratum: A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells
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4,056 |
Correction: Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations
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4,057 |
Geng et al. reply
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4,058 |
Shifting to very early endoscopic DCR in acute suppurative dacryocystitis
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PURPOSE: We aimed to show the outcome of very early endoscopic dacryocystorhinostomy (VE-EDCR) in a routine pool of patients with acute dacryocystitis (AD) and abscess formation compared with the standard late external dacryocystorhinostomy L-ExDCR. METHODS: This was a prospective nonrandomized comparative study conducted from June 2013 to March 2016. Patients with AD and abscess formation were referred to our oculo-facial clinic in a university-based hospital. All patients received systemic antibiotics and were assigned to either of treatment groups. Patients in group 1 underwent late external transcutaneous DCR (L-ExDCR) and group 2 underwent EDCR within 3 days after first visit, named VE-EDCR. Primary outcome measure was success of surgery. RESULTS: Forty-one eyes of 41 patients with acute suppurative AD, were included from June 2013 to March 2016. Twenty-two patients underwent VE-EDCR and 19 underwent L-ExDCR. Mean age of patients was 43.41 (SD = 19.84, range 14–98) years. Mean follow-up was 14 (SD = 2.4) months. Anatomic, functional, and overall success in L-ExDCR and VE-EDCR groups were (89.5 and 86.4%, p = 0.99) (89.5% and 86.4%, p = 0.99) (89.5% and 81.8%, p = 0.66) respectively. Mean duration of cellulitis in VE-EDCR and L-ExDCR were 8.00 (SD = 4.63) and 16.11 (SD = 11.58) days, respectively (p = 0.027). No remarkable adverse event was found. CONCLUSIONS: Success of very early endonasal endoscopic DCR is comparable with the traditional late external DCR. Duration of cellulitis is shorter in VE-EDCR. This therapeutic approach can be considered in patients with acute suppurative dacryocystitis.
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4,059 |
Seeing is believing: a novel tool for quantitating mitophagy
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4,060 |
Outcomes and complications of iris-fixated intraocular lenses in cases with inadequate capsular support and complex ophthalmic history
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BACKGROUND: To report the indications, visual outcomes, and intra-operative and post-operative complications of iris-sutured posterior chamber intraocular lens (IOL) in eyes with inadequate capsular support and complex ocular history. METHODS: A chart review and data analysis of eyes that underwent iris fixation of posterior chamber (PC) IOL for correction of aphakia, dislocated and subluxed IOLs, ectopia lentis, and IOL exchange. Data included clinical risk factors, associated eye conditions, previous surgeries, and concomitant procedures. The pre-operative and post-operative vision, manifest refraction, endothelial cell density, intraocular pressure (IOP), as well as intra-operative and post-operative complications were also recorded. RESULTS: One hundred and seventeen eyes from 114 patients were examined with a mean follow-up of 22.4 months. The most common identifiable predisposing risk factor was high myopia in 23 eyes. A significant improvement in uncorrected and best corrected visual acuity compared with baseline was observed. The most common post-operative complications included recurrent IOL subluxation in 16 (13.7%) eyes, IOP spike in 7 (5.9%) eyes, cystoid macular oedema in 5 (4.3%) eyes, and epiretinal membrane formation in 4 (3.4%) eyes. There was one (0.85%) case of sterile endophthalmitis. CONCLUSIONS: Iris suture fixation of PC IOLs is a good treatment option for eyes with inadequate capsular support and complex ocular history.
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4,061 |
Erratum: Arc expression identifies the lateral amygdala fear memory trace
| null |
4,062 |
SRD5A3 defective congenital disorder of glycosylation: clinical utility gene card
| null |
4,063 |
Erratum: Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia
| null |
4,064 |
A serine protease inhibitor induces type 1 regulatory T cells through IFN-γ/STAT1 signaling
| null |
4,065 |
Response to ‘Comment on: ophthalmology specialist trainee survey in the United Kingdom’
| null |
4,066 |
Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder
|
Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg(−1)) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.
|
4,067 |
Correction to: Transpiration and growth of young African mahogany plants subject to different water regimes
| null |
4,068 |
Erratum: PML is required for telomere stability in non-neoplastic human cells
| null |
4,069 |
Erratum: Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention
| null |
4,070 |
Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation
| null |
4,071 |
Correction: Connectomics of bipolar disorder: a critical review, and evidence for dynamic instabilities within interoceptive networks
| null |
4,072 |
Amblyopia, deprivation and health disparities research: challenges in 2020
| null |
4,073 |
Professional duties are now considered legal duties of care within genomic medicine
|
The legal duty to protect patient confidentiality is common knowledge amongst healthcare professionals. However, what may not be widely known, is that this duty is not always absolute. In the United Kingdom, both the General Medical Council governing the practice of all doctors, as well as many other professional codes of practice recognise that, under certain circumstances, it may be appropriate to break confidentiality. This arises when there is a wider duty to protect the health of others, and when the risk of non-disclosure outweighs the potential harm from breaking confidentiality. We discuss this situation specifically in relation to genomic medicine where relatives in a family may have differing views on the sharing of familial genetic information. Overruling a patient’s wishes is predicated on balancing the duty of care towards the patient versus protecting their relative from serious harm. We discuss the practice implications of a pivotal legal case that concluded recently in the High Court of Justice in England and Wales, ABC v St Georges Healthcare NHS Trust & Ors. Professional guidance is already clear that genetic healthcare professionals must undertake a balancing exercise to weigh up contradictory duties of care. However, the judge has provided a new legal weighting to these professional duties: ‘The scope of the duty extends not only to conducting the necessary balancing exercise but also to acting in accordance with its outcome’ [1: 189]. In the context of genomic medicine, this has important consequences for clinical practice.
|
4,074 |
A systematic review of simulation-based training tools for technical and non-technical skills in ophthalmology
|
To evaluate all simulation models for ophthalmology technical and non-technical skills training and the strength of evidence to support their validity and effectiveness. A systematic search was performed using PubMed and Embase for studies published from inception to 01/07/2019. Studies were analysed according to the training modality: virtual reality; wet-lab; dry-lab models; e-learning. The educational impact of studies was evaluated using Messick’s validity framework and McGaghie’s model of translational outcomes for evaluating effectiveness. One hundred and thirty-one studies were included in this review, with 93 different simulators described. Fifty-three studies were based on virtual reality tools; 47 on wet-lab models; 26 on dry-lab models; 5 on e-learning. Only two studies provided evidence for all five sources of validity assessment. Models with the strongest validity evidence were the Eyesi Surgical, Eyesi Direct Ophthalmoscope and Eye Surgical Skills Assessment Test. Effectiveness ratings for simulator models were mostly limited to level 2 (contained effects) with the exception of the Sophocle vitreoretinal surgery simulator, which was shown at level 3 (downstream effects), and the Eyesi at level 5 (target effects) for cataract surgery. A wide range of models have been described but only the Eyesi has undergone comprehensive investigation. The main weakness is in the poor quality of study design, with a predominance of descriptive reports showing limited validity evidence and few studies investigating the effects of simulation training on patient outcomes. More robust research is needed to enable effective implementation of simulation tools into current training curriculums.
|
4,075 |
A dominant vimentin variant causes a rare syndrome with premature aging
|
Progeroid syndromes are a group of rare genetic disorders, which mimic natural aging. Unraveling the molecular defects in such conditions could impact our understanding of age-related syndromes such as Alzheimer’s or cardiovascular diseases. Here we report a de novo heterozygous missense variant in the intermediate filament vimentin (c.1160 T > C; p.(Leu387Pro)) causing a multisystem disorder associated with frontonasal dysostosis and premature aging in a 39-year-old individual. Human vimentin p.(Leu387Pro) expression in zebrafish perturbed body fat distribution, and craniofacial and peripheral nervous system development. In addition, studies in patient-derived and transfected cells revealed that the variant affects vimentin turnover and its ability to form filaments in the absence of wild-type vimentin. Vimentin p.(Leu387Pro) expression diminished the amount of peripilin and reduced lipid accumulation in differentiating adipocytes, recapitulating key patient’s features in vivo and in vitro. Our data highlight the function of vimentin during development and suggest its contribution to natural aging.
|
4,076 |
Correction to: ROS and diseases: role in metabolism and energy supply
| null |
4,077 |
Correction: CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer
| null |
4,078 |
Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
| null |
4,079 |
Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States
|
BACKGROUND/OBJECTIVES: Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians’ comfort working up, diagnosing, and managing ophthalmic emergencies. SUBJECTS/METHODS: 329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies. RESULTS: Participants recall receiving a median of 5 and 10 h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians. CONCLUSIONS: Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula.
|
4,080 |
Correction: Corrigendum: Genetic diagnosis of Duchenne/Becker muscular dystrophy using next-generation sequencing: validation analysis of DMD mutations
| null |
4,081 |
Making ends meet in class switch recombination
| null |
4,082 |
The choice of analysis of variance models in repeated measurements analysis—on the effect of glaucoma surgery on retinal structures
| null |
4,083 |
Author Correction: Biofortification of field-grown cassava by engineering expression of an iron transporter and ferritin
| null |
4,084 |
Correction: Comment on: ‘Recent advances in anterior chamber angle imaging’
| null |
4,085 |
High rate of HDR in gene editing of p.(Thr158Met) MECP2 mutational hotspot
|
Rett syndrome is a progressive neurodevelopmental disorder which affects almost exclusively girls, caused by variants in MECP2 gene. Effective therapies for this devastating disorder are not yet available and the need for tight regulation of MECP2 expression for brain to properly function makes gene replacement therapy risky. For this reason, gene editing with CRISPR/Cas9 technology appears as a preferable option for the development of new therapies. To study the disease, we developed and characterized a human neuronal model obtained by genetic reprogramming of patient-derived primary fibroblasts into induced Pluripotent Stem Cells. This cellular model represents an important source for our studies, aiming to correct MECP2 variants in neurons which represent the primarily affected cell type. We engineered a gene editing toolkit composed by a two-plasmid system to correct a hotspot missense variant in MECP2, c.473 C > T (p.(Thr158Met)). The first construct expresses the variant-specific sgRNA and the Donor DNA along with a fluorescent reporter system. The second construct brings Cas9 and targets for auto-cleaving, to avoid long-term Cas9 expression. NGS analysis on sorted cells from four independent patients demonstrated an exceptionally high editing efficiency, with up to 80% of HDR and less than 1% of indels in all patients, outlining the relevant potentiality of the approach for Rett syndrome therapy.
|
4,086 |
Correction: O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit
| null |
4,087 |
Correction: Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells
| null |
4,088 |
EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency
|
Molecular genetic testing for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is offered worldwide and is of importance for differential diagnosis, carrier detection and adequate genetic counseling, particularly for family planning. In 2008 the European Molecular Genetics Quality Network (EMQN) for the first time offered a European-wide external quality assessment scheme for CAH (due to 21-OH deficiency). The interest was great and over the last years at about 60 laboratories from Europe, USA and Australia regularly participated in that scheme. These best practice guidelines were drafted on the basis of the extensive knowledge and experience got from those annually organized CAH-schemes. In order to obtain the widest possible consultation with practicing laboratories the draft was therefore circulated twice by EMQN to all laboratories participating in the EQA-scheme for CAH genotyping and was updated by that input. The present guidelines address quality requirements for diagnostic molecular genetic laboratories, as well as criteria for CYP21A2 genotyping (including carrier-testing and prenatal diagnosis). A key aspect of that article is the use of appropriate methodologies (e.g., sequencing methods, MLPA (multiplex ligation dependent probe amplification), mutation specific assays) and respective limitations and analytical accuracy. Moreover, these guidelines focus on classification of variants, and the interpretation and standardization of the reporting of CYP21A2 genotyping results. In addition, the article provides a comprehensive list of common as well as so far unreported CYP21A2-variants.
|
4,089 |
Quality of life drives patients’ preferences for secondary findings from genomic sequencing
|
There is growing impetus to include measures of personal utility, the nonmedical value of information, in addition to clinical utility in health technology assessment (HTA) of genomic tests such as genomic sequencing (GS). However, personal utility and clinical utility are challenging to define and measure. This study aimed to explore what drives patients’ preferences for hypothetically learning medically actionable and non-medically actionable secondary findings (SF), capturing clinical and personal utility; this may inform development of measures to evaluate patient outcomes following return of SF. Semi-structured interviews were conducted with adults with a personal or family cancer history participating in a trial of a decision aid for selection of SF from genomic sequencing (GS) (www.GenomicsADvISER.com). Interviews were analyzed thematically using constant comparison. Preserving health-related and non-health-related quality of life was an overarching motivator for both learning and not learning SF. Some participants perceived that learning SF would help them “have a good quality of life” through informing actions to maintain physical health or leading to psychological benefits such as emotional preparation for disease. Other participants preferred not to learn SF because results “could ruin your quality of life,” such as by causing negative psychological impacts. Measuring health-related and non-health-related quality of life may capture outcomes related to clinical and personal utility of GS and SF, which have previously been challenging to measure. Without appropriate measures, generating and synthesizing evidence to evaluate genomic technologies such as GS will continue to be a challenge, and will undervalue potential benefits of GS and SF.
|
4,090 |
Erratum: Infrequently expressed miRNAs in colorectal cancer tissue and tumor molecular phenotype
| null |
4,091 |
Ecological succession in the vaginal microbiota during pregnancy and birth
|
The mother’s vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.
|
4,092 |
Linking perturbations to temporal changes in diversity, stability, and compositions of neonatal calf gut microbiota: prediction of diarrhea
|
Perturbations in early life gut microbiota can have long-term impacts on host health. In this study, we investigated antimicrobial-induced temporal changes in diversity, stability, and compositions of gut microbiota in neonatal veal calves, with the objective of identifying microbial markers that predict diarrhea. A total of 220 samples from 63 calves in first 8 weeks of life were used in this study. The results suggest that increase in diversity and stability of gut microbiota over time was a feature of “healthy” (non-diarrheic) calves during early life. Therapeutic antimicrobials delayed the temporal development of diversity and taxa–function robustness (a measure of microbial stability). In addition, predicted genes associated with beta lactam and cationic antimicrobial peptide resistance were more abundant in gut microbiota of calves treated with therapeutic antimicrobials. Random forest machine learning algorithm revealed that Trueperella, Streptococcus, Dorea, uncultured Lachnospiraceae, Ruminococcus 2, and Erysipelatoclostridium may be key microbial markers that can differentiate “healthy” and “unhealthy” (diarrheic) gut microbiota, as they predicted early life diarrhea with an accuracy of 84.3%. Our findings suggest that diarrhea in veal calves may be predicted by the shift in early life gut microbiota, which may provide an opportunity for early intervention (e.g., prebiotics or probiotics) to improve calf health with reduced usage of antimicrobials.
|
4,093 |
Correction: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance
| null |
4,094 |
Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice
|
High dose intake of docosahexaenoic acid showed beneficial effects on atopic dermatitis in patients and was found to increase regulatory T cells in mice, but its molecular target has not been identified. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor sensing polyunsaturated long-chain fatty acids including docosahexaenoic acid. In the present study, we examined whether FFA4 acted as a therapeutic target of docosahexaenoic acid for treating atopic dermatitis. Experimental atopic dermatitis was induced in mice by 2,4-dinitrochlorobenzene (DNCB) sensitization on day 0, followed by repeated DNCB challenges from D7 to D48. The mice were treated with a selective agonist compound A (30 mg· kg(−1)· d(−1), ip) from D19 to D48, and sacrificed on D49. We found that DNCB-induced atopic dermatitis-like skin lesions, i.e. hypertrophy and mast cell infiltration in skin tissues, as well as markedly elevated serum IgE levels. Administration of compound A significantly suppressed the atopic responses in ears and lymph nodes, such as hypertrophy and mast cell infiltration in the ears, enlarged sizes of lymph nodes, and elevated serum IgE and levels of cytokines IL-4, IL-13, IL-17, and IFN-γ in ear tissue. The therapeutic effects of compound A were abolished by FFA4 knockout. Similarly, increased CD4(+)Foxp3(+) regulatory T-cell population in lymph nodes was observed in wide-type mice treated with compound A, but not seen in FFA4-deficient mice. In conclusion, we demonstrate that activation of FFA4 ameliorates atopic dermatitis by increasing CD4(+)Foxp3(+) regulatory T cells, suggesting FFA4 as a therapeutic target for atopic dermatitis.
|
4,095 |
Author Correction: 863 genomes reveal the origin and domestication of chicken
| null |
4,096 |
Publisher Correction: Definitions and guidelines for research on antibiotic persistence
| null |
4,097 |
Erratum: Common alleles contribute to schizophrenia in CNV carriers
| null |
4,098 |
Correction: The Epstein–Barr virus nuclear antigen-1 upregulates the cellular antioxidant defense to enable B-cell growth transformation and immortalization
| null |
4,099 |
Author Correction: Liriodendron genome sheds light on angiosperm phylogeny and species–pair differentiation
| null |
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