Abstract
The Encyclopedia of DNA Elements (ENCODE) is an ongoing collaborative research project aimed at identifying all the functional elements in the human and mouse genomes. Data generated by the ...ENCODE consortium are freely accessible at the ENCODE portal (https://www.encodeproject.org/), which is developed and maintained by the ENCODE Data Coordinating Center (DCC). Since the initial portal release in 2013, the ENCODE DCC has updated the portal to make ENCODE data more findable, accessible, interoperable and reusable. Here, we report on recent updates, including new ENCODE data and assays, ENCODE uniform data processing pipelines, new visualization tools, a dataset cart feature, unrestricted public access to ENCODE data on the cloud (Amazon Web Services open data registry, https://registry.opendata.aws/encode-project/) and more comprehensive tutorials and documentation.
Chromatin looping is key to gene regulation, yet no broadly applicable methods to selectively modify chromatin loops have been described. We have engineered a method for chromatin loop reorganization ...using CRISPR-dCas9 (CLOuD9) to selectively and reversibly establish chromatin loops. We demonstrate the power of this technology to selectively modulate gene expression at targeted loci.
Hepatic ischemia/reperfusion injury (IRI) is an unavoidable course in liver transplantation, during which the immune response of inflammation plays a leading part. MicroRNA-450b-5p (miR-450b-5p), ...which has been reported to participate in several inflammatory diseases, was investigated in this study. The purpose of this study is to identify the potential function of miR-450b-5p toward remission of hepatic IRI and elucidate the specific mechanism. Herein we found that expression of miR-450b-5p, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 was stimulated in hepatic IRI. Inhibition of miR-450b-5p could remarkably alleviate mouse hepatic IRI and improve liver function measured by hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA). We further assessed protein expression undergoing Western blot and immunofluorescence, and discovered that miR-450b-5p suppressed alpha B-crystallin (CRYAB), thus restraining the inhibitory κB kinase (IKK) β-mediated canonical nuclear factor-κB (NF-κB) signaling, instead of the noncanonical path guided by IKKα in hepatic IRI. In addition, we demonstrated CRYAB as an activator of M2 polarization through protein kinase B (Akt) 1/mammalian target of rapamycin (mTOR), thus resulting in relief of liver IRI. Combination treatment containing both paths revealed a better antidamage efficacy than adjusting either path alone, suggesting that the joint therapy might be a promising solution in hepatic IRI.
Hepatic ischemia/reperfusion (I/R) injury occurs frequently in various liver operations and diseases, but its effective treatment remains inadequate because the key switch that leads to hepatic ...explosive inflammation has not been well disclosed. Dual specificity phosphatase 9 (DUSP9) is widely involved in the innate immune response of solid organs and is sometimes regulated by ubiquitin. In the present study, we find that DUSP9 is reduced in mouse hepatic I/R injury. DUSP9 enrichment attenuates hepatic inflammation both
and
as revealed by western blot analysis and qRT-PCR. In contrast, DUSP9 depletion leads to more severe I/R injury. Mechanistically, DUSP9 inhibits the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) by directly binding to ASK1, thereby decreasing tumor necrosis factor receptor-associated factor 6 (TRAF6), K63 ubiquitin and the phosphorylation of p38/JNK1 instead of ERK1. The present study documents a novel role of DUSP9 in hepatic I/R injury and implies the potential of targeting the DUSP9/ASK1 axis towards mitogen-activated protein kinase and TRAF6/inhibitor of κB kinase pathways.
Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes associated with various liver surgeries. However, there is still a lack of strategies to protect against hepatic ...I/R injury because of the unknown underlying mechanism. The present study aimed to identify a potential strategy and provide a fundamental experimental basis for treating hepatic I/R injury.
A classic 70% ischemia/reperfusion injury was established. Immunoprecipitation was used to identify direct interactions between proteins. The expression of proteins from different subcellular localizations was detected by Western blotting. Cell translocation was directly observed by immunofluorescence. HE, TUNEL and ELISA were performed for function tests.
We report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through the reinforcement of IKK-induced inflammation following dual patterns. Mechanistically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), inducing K63 ubiquitination and eventually leading to the phosphorylation of IKKβ. TRIM37 enhances the translocation of IKKγ, a regulatory subunit of the IKK complex, from the nucleus to the cytoplasm, thereby stabilizing the cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK rescued the function of TRIM37 in vivo and in vitro.
Collectively, the present study discloses some potential function of TRIM37 in hepatic I/R injury. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.Targeting TRIM37 might be a potential treatment strategy against hepatic I/R injury.
Abstract
Background
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is one of the most common and deadly cancer and often accompanied by varying degrees of liver damage, leading to ...the dysfunction of fatty acid metabolism (FAM). This study aimed to investigate the relationship between FAM and HBV-associated HCC and identify FAM biomarkers for predicting the prognosis of HBV-associated HCC.
Methods
Gene Set Enrichment Analysis (GSEA) was used to analyze the difference of FAM pathway between paired tumor and adjacent normal tissue samples in 58 HBV-associated HCC patients from the Gene Expression Omnibus (GEO) database. Next, 117 HBV-associated HCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to establish a prognostic signature based on 42 FAM genes. Then, the prognostic signature was validated in an external cohort consisting of 30 HBV-associated HCC patients. Finally, immune infiltration analysis was performed to evaluate the FAM-related immune cells in HBV-associated HCC.
Results
As a result, FAM pathway was clearly downregulated in tumor tissue of HBV-associated HCC, and survival analysis demonstrated that 12 FAM genes were associated with the prognosis of HBV-associated HCC. Lasso-penalized Cox regression analysis identified and established a five-gene signature (ACADVL, ACAT1, ACSL3, ADH4 and ECI1), which showed effective discrimination and prediction for the prognosis of HBV-associated HCC both in the TCGA cohort and the validation cohort. Immune infiltration analysis showed that the high-risk group, identified by FAM signature, of HBV-associated HCC had a higher ratio of Tregs, which was associated with the prognosis.
Conclusions
Collectively, these findings suggest that there is a strong connection between FAM and HBV-associated HCC, indicating a potential therapeutic strategy targeting FAM to block the accumulation of Tregs into the tumor microenvironment of HBV-associated HCC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neutrophil extracellular traps (NETs) play important roles in hepatic ischemic reperfusion injury (IRI) and acute rejection (AR)-induced immune responses to inflammation. After liver transplantation, ...HMGB1, an inflammatory mediator, contributes to the development of AR. Even though studies have found that HMGB1 can promote NET formation, the correlation between NETs and HMGB1 in the development of AR following liver transplantation has not been elucidated. In this study, levels of serum NETs were significantly elevated in patients after liver transplantation. Moreover, we found that circulating levels of NETs were negatively correlated with liver function. In addition, liver transplantation and elevated extracellular HMGB1 promoted NET formation. The HMGB1/TLR-4/MAPK signaling pathway, which is initiated by HMGB1, participates in NET processes. Moreover, in the liver, Kupffer cells were found to be the main cells secreting HMGB1. NETs induced Kupffer cell M1 polarization and decreased the intracellular translocation of HMGB1 by inhibiting DNase-1. Additionally, co-treatment with TAK-242 (a TLR-4 inhibitor) and rapamycin more effectively alleviated the damaging effects of AR following liver transplantation than either drug alone.
Objective
This is the first systematic review and meta-analysis to determine the factors that contribute to poor antibody response in organ transplant recipients after receiving the 2-dose severe ...acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.
Method
Data was obtained from Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM). Studies reporting factors associated with antibody responses to the 2-dose SARS-CoV-2 vaccine in solid organ transplant recipients were included in our study based on the inclusion and exclusion criteria. Two researchers completed the literature search, screening, and data extraction. Randomized models were used to obtain results. Egger’s test was performed to determine publication bias. Sensitivity analysis was performed to determine the stability of the result. The heterogeneity was determined using the Galbraith plot and subgroup analysis.
Results
A total of 29 studies were included in the present study. The factors included living donor, BNT162b2, tacrolimus, cyclosporine, antimetabolite, mycophenolic acid (MPA) or mycophenolate mofetil (MMF), azathioprine, corticosteroids, high-dose corticosteroids, belatacept, mammalian target of rapamycin (mTOR) inhibitor, tritherapy, age, estimated glomerular filtration rate (eGFR), hemoglobin, and tacrolimus level were significantly different. Multivariate analysis showed significant differences in age, diabetes mellitus, MPA or MMF, high-dose corticosteroids, tritherapy, and eGFR.
Conclusion
The possible independent risk factors for negative antibody response in patients with organ transplants who received the 2-dose SARS-CoV-2 vaccine include age, diabetes mellitus, low eGFR, MPA or MMF, high-dose corticosteroids, and triple immunosuppression therapy. mTOR inhibitor can be a protective factor against weak antibody response.
Systematic Review Registration
PROSPERO, identifier CRD42021257965.
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