Publications by authors named "Chuan He"

669 Publications

Concentration and atmospheric transport of PM-bound polycyclic aromatic hydrocarbons at Mount Tai, China.

Sci Total Environ 2021 May 5;786:147513. Epub 2021 May 5.

Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Key Laboratory for Aerosol-Cloud-Precipitation of China Meteorological Administration, Nanjing University of Information Science & Technology, Nanjing 210044, China.

Atmospheric PM-bound polycyclic aromatic hydrocarbons (PAHs) pose a major threat to human health. At present, studies on PAHs in the atmosphere have mostly focused on their concentration levels and source apportionment, whereas studies on the vertical transport of PAHs in the atmosphere are limited. However, the vertical transport of PAHs is important for their diffusion near the ground and their long-range transport at higher altitude. In this study, PM samples were collected simultaneously at the summit and foot of Mount Tai (MT and MT, respectively) from May to June 2017, and the concentrations of 18 PAHs in the samples were determined. The total concentration of PAHs at MT was 2.406 ng m, which was well below the pollution levels of domestic cities, whereas that at MT was as high as 9.068 ng m, which was within the range of pollution levels in domestic cities. The total carcinogenic risk for both MT and MT was within the potential risk range. Given the source of PAHs and the diurnal variation of the planetary boundary layer, the PAHs showed opposite diurnal trends at MT and MT. Vertical transport was an important source of daytime PAHs at MT, and the vertical transport efficiency of PAHs decreased with an increasing ring number; this may be due to the combined effects of gas-particle partitioning and chemical reactions. Furthermore, PAHs originating in the surrounding high-emission provinces can affect the Mount Tai area via atmospheric trans-regional transport, and the BaP/BeP ratio is a useful indicator of the transport distance of PAHs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.147513DOI Listing
May 2021

DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

Adv Sci (Weinh) 2021 05 1;8(9):2004793. Epub 2021 Mar 1.

Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China.

Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1 mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA (HA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed HA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202004793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097319PMC
May 2021

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma.

Front Oncol 2021 19;11:654350. Epub 2021 Apr 19.

Center of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: CD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).

Methods: The prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using r package to reveal potential pathways.

Results: Pan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.

Conclusions: Integrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.654350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089378PMC
April 2021

FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy.

Acta Pharmacol Sin 2021 Apr 20. Epub 2021 Apr 20.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China.

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC values of 135.75, 128.26, 142.65, 155.73 and 111.60 μM, respectively. In U87 and U251 cells, TMZ (200 μM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg·d, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41401-021-00663-yDOI Listing
April 2021

[A cadaveric experimental study on domestic robot-assisted total knee arthroplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):409-413

Department of Orthopedics, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, P.R.China.

Objective: To simulate and validate the performance, accuracy, and safety of the Yuanhua robotic-assisted total knee arthroplasty system (YUANHUA-TKA) through cadaver-based experiment, thus optimizing the robotic system for the future human clinical application.

Methods: Six unilateral adult cadaver specimens of the lower limbs were scanned by three-dimensional CT before the experiment, and then the three-dimensional models of femur and tibia were obtained by using the preoperative software of YUANHUA-TKA system, so as to plan the type of prosthesis implant, the osteotomy volume and osteotomy angles [hip-knee-ankle angle (HKA), coronal frontal femoral component (FFC) and frontal tibial component (FTC)], the ideal value of HKA was set to 180°, and of FFC and FTC were set to 90°, respectively. The operator could further confirm the osteotomy plan according to the intraoperative situation before osteotomy, and then install the prosthesis after completing the osteotomy in each plane with the assistance of YUANHUA-TKA system. At last, the X-ray films of hip joint, knee joint, and ankle joint were taken and stitched into the full length X-ray film of the lower limb, and HKA, coronal FFC and FTC were measured.

Results: During the experiment, YUANHUA-TKA system ran stably. All sections of femur and tibia were smooth and no ligament injury was found. After operation, the HKA was 177.1°-179.7°, FFC was 87.9°-91.4°, and FTC was 87.3°-91.4°, which were within ±3° from the ideal values of preoperative planning.

Conclusion: The YUANHUA-TKA system can assist the surgeon to carry out precise osteotomy according to the preoperative planned value, which has a good auxiliary effect for total knee arthroplasty. It is expected to assist joint surgeons to improve the surgical accuracy in clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7507/1002-1892.202010021DOI Listing
April 2021

Current Knowledge of and Perspectives about the Pathogenesis of Blood Blister-like Aneurysms of the Internal Carotid Artery: A Review of the Literature.

Int J Med Sci 2021 3;18(9):2017-2022. Epub 2021 Mar 3.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Blood blister-like aneurysms (BBAs) are rare and usually appear at nonbranching sites in the supraclinoid portion of the internal carotid artery (ICA). Because it is difficult to obtain histological specimens of the aneurysm wall and because experimental models are challenging to establish, the pathogenesis of BBAs remains uncertain. In this paper, we reviewed the diagnostic, radiological, and pathophysiological characteristics of patients with BBAs. We also summarized the existing evidence and potential mechanisms related to the causes of BBAs. Current evidence indicates that atherosclerosis and dissection are the main prerequisites for the formation of BBAs. Hemodynamics may play a role in the process of BBA formation due to the unique vascular anatomy of the supraclinoid ICA. Further research on histopathology and hemodynamics is warranted in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.53154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040398PMC
March 2021

Autophagy of the mA mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis.

Nat Commun 2021 04 12;12(1):2183. Epub 2021 Apr 12.

Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA.

Here we show that FTO as an N-methyladenosine (mA) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while mA RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated mA RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We identified NEDD4L as the mA-modified gene target of FTO. Finally, arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO upregulation can in turn inhibit autophagy, leading to a positive feedback loop to maintain FTO accumulation. Our study reveals FTO-mediated dysregulation of mRNA mA methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22469-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041927PMC
April 2021

QSER1 protects DNA methylation valleys from de novo methylation.

Science 2021 04;372(6538)

Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.

DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators. The top screen hit was an uncharacterized gene, , which proved to be a key guardian of bivalent promoters and poised enhancers of developmental genes, especially those residing in DNA methylation valleys (or canyons). We further demonstrate genetic and biochemical interactions of QSER1 and TET1, supporting their cooperation to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abd0875DOI Listing
April 2021

Catalytic Asymmetric Synthesis of Silicon-Stereogenic Dihydrodibenzosilines: Silicon-Central to Axial Chirality Relay.

Angew Chem Int Ed Engl 2021 Apr 8. Epub 2021 Apr 8.

Southern University of Science and Technology, Chemistry, CHINA.

A Rh-catalyzed asymmetric synthesis of silicon-stereogenic dihydrodibenzosilines featuring axially chiral 6-member-bridged biaryls is demonstrated. In the presence of Rh(I) catalyst with chiral diphosphine ligand, a wide range of dihydrodibenzosilines containing both silicon-central and axial chiralities are conveniently constructed in excellent enantioselectivities via dehydrogenative Csp3-H silylation. Absolute configuration analysis by single crystal X-ray structures revealed a novel silicon-central to axial chirality relay phenomenon, which we believe will inspire further research in the field of asymmetric catalysis and chiroptical materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202103748DOI Listing
April 2021

A novel method to establish the rabbit model of knee osteoarthritis: intra-articular injection of SDF-1 induces OA.

BMC Musculoskelet Disord 2021 Apr 3;22(1):329. Epub 2021 Apr 3.

Departments of Sports Medicine, The First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, 650032, P.R. China.

Background: Animal model of Knee Osteoarthritis (OA) is the primary testing methodology for studies on pathogenic mechanisms and therapies of human OA disease. Recent major modeling methods are divided into artificially induced and spontaneous. However, these methods have some disadvantages of slow progression, high cost and no correlation with the pathogenesis of OA.

Methods: Our studies attempted to find a rapid, easy, and consistent with the natural pathological process of OA modeling method by intra-articular injection of stromal cell-derived factor 1 (SDF-1) in the rabbit knee. After induction we collected cartilage specimens from the medial femoral condyle to undergo macroscopic, histological, immunohistochemical, and biochemical evaluations. Meanwhile, compared with Hulth surgical method to evaluate its efficacy.

Results: Macroscopic observation and modified Mankin score of histological staining exhibited typical features of middle stage OA cartilage in SDF-1 injected groups. Immunohistochemically, the positive expression of interleukin-1 (IL-1) and tumor necrosis factor α(TNF-α) was earlier and higher in high dose SDF-1 group than the surgical group. The matrix metalloproteinases (MMPs) in synovial fluid and chondrocytes significantly increased, but type II collagen (COLII) and aggrecan (ACAN) protein expressions decreased in SDF-1 injected group following the extension of time and increase of SDF-1 concentration.

Conclusions: Our data indicated intra-articular injection of SDF-1 (40μg/kg, three times for 12 weeks) can induce rabbit knee OA model successfully more rapidly and easily than traditional surgical modeling. The study provided a further option for the establishment of knee OA animal model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-021-04188-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019508PMC
April 2021

Catalytic Enantioselective Dehydrogenative Si-O Coupling to Access Chiroptical Silicon-Stereogenic Siloxanes and Alkoxysilanes.

J Am Chem Soc 2021 Apr 1;143(14):5301-5307. Epub 2021 Apr 1.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

A rhodium-catalyzed enantioselective construction of triorgano-substituted silicon-stereogenic siloxanes and alkoxysilanes is developed. This process undergoes a direct intermolecular dehydrogenative Si-O coupling between dihydrosilanes with silanols or alocohols, giving access to a variety of highly functionalized chiral siloxanes and alkoxysilanes in decent yields with excellent control, that significantly expand the chemical space of the silicon-centered chiral molecules. Further utility of this process was illustrated by the construction of CPL-active (circularly polarized luminescence) silicon-stereogenic alkoxysilane small organic molecules. Optically pure bis-alkoxysilane containing two silicon-stereogenic centers and three pyrene groups displayed a remarkable value with a high fluorescence quantum efficiency ( = 0.011, Φ = 0.55), which could have great potential application prospects in chiral organic optoelectronic materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c01106DOI Listing
April 2021

Paired-like homeodomain transcription factor 2 strengthens chemoresistance in colorectal cancer by activating the Wnt/β-catenin axis.

Neoplasma 2021 Mar 30. Epub 2021 Mar 30.

Department of Gastroenterology, Jiangxi Cancer Hospital, Nanchang, Jiangxi , China.

The purpose of this study was to determine the mechanism of paired-like homeodomain transcription factor 2 (PITX2) in the chemoresistance of colorectal cancer (CRC) via the upregulation of the Wnt/β-catenin axis. CRC cells were persistently exposed to increasing 5-fluorouracil (5-FU) concentrations to establish 5-FU-resistant cells. Functional assays were conducted to examine cell viability, proliferation, and cell cycle. After the transfection of small interfering (si)-negative control and si-PITX2 in 5-FU-resistant cells, the effects of PITX2 depletion in these cells were assessed. Notably, expression of PITX2, Wnt-3a, and β-catenin, and the relation between PITX2 and Wnt-3a were verified. Additionally, an inhibitor or an activator of the Wnt/β-catenin axis was added into cells to detect the variance of the 5-FU-resistant cells. Eventually, xenograft transplantation was applied to confirm the effect of PITX2 knockdown on CRC chemoresistance to 5-FU. 5-FU-resistant CRC cells were successfully established, in which CRC cell viability, proliferation, and cell cycle were all enhanced, while PITX2 knockout led to reversed results, indicating that resistance to 5-FU in CRC was restricted. Furthermore, our findings revealed that PITX2 upregulated the Wnt/β-catenin axis. The inactivation of the Wnt/β-catenin axis resulted in the reduction of resistance to 5-FU in CRC cells; while activation of the Wnt/β-catenin axis reversed the reduced resistance to 5-FU in CRC cells caused by PITX2 knockout. Additionally, xenograft transplantation further confirmed that PITX2 knockdown reduced the resistance of HCT116 cells to 5-FU. This study clarified that PITX2 enhanced resistance to 5-FU in CRC upregulating the Wnt/β-catenin axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4149/neo_2021_201031N1156DOI Listing
March 2021

N -methyladenosine modification of lncRNA Pvt1 governs epidermal stemness.

EMBO J 2021 Apr 17;40(8):e106276. Epub 2021 Mar 17.

Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, USA.

Dynamic chemical modifications of RNA represent novel and fundamental mechanisms that regulate stemness and tissue homeostasis. Rejuvenation and wound repair of mammalian skin are sustained by epidermal progenitor cells, which are localized within the basal layer of the skin epidermis. N -methyladenosine (m A) is one of the most abundant modifications found in eukaryotic mRNA and lncRNA (long noncoding RNA). In this report, we survey changes of m A RNA methylomes upon epidermal differentiation and identify Pvt1, a lncRNA whose m A modification is critically involved in sustaining stemness of epidermal progenitor cells. With genome-editing and a mouse genetics approach, we show that ablation of m A methyltransferase or Pvt1 impairs the self-renewal and wound healing capability of skin. Mechanistically, methylation of Pvt1 transcripts enhances its interaction with MYC and stabilizes the MYC protein in epidermal progenitor cells. Our study presents a global view of epitranscriptomic dynamics that occur during epidermal differentiation and identifies the m A modification of Pvt1 as a key signaling event involved in skin tissue homeostasis and wound repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020106276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047438PMC
April 2021

Chromatin and transcriptional regulation by reversible RNA methylation.

Curr Opin Cell Biol 2021 Jun 9;70:109-115. Epub 2021 Mar 9.

Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL, 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL, 60637, USA. Electronic address:

Dynamic RNA modifications have been a burgeoning area in the last decade since the concept of 'RNA epigenetics' was proposed [1]. N-methyladenosine (mA) is the most abundant mRNA modification in eukaryotic cells. It can be installed by 'writers', removed by 'erasers,' recognized by 'readers,' and dynamically regulate the fate of methylated RNA. Until recently, the roles of reversible RNA methylation in chromatin and transcriptional regulation were not adequately studied. We discuss the new discoveries and insights into the chromatin and transcriptional regulation by mA through two pathways: 1) effects of mA on mRNAs encoding histone modifiers and transcriptional factors; 2) mA regulation of chromatin-associated regulatory RNAs. Additionally, we provide an outlook on how the transcriptional regulation by RNA mA could add an additional critical layer to transcriptional regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ceb.2020.11.005DOI Listing
June 2021

N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages.

PLoS Pathog 2021 Mar 10;17(3):e1009421. Epub 2021 Mar 10.

Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.

N6-methyladenosine (m6A) is a prevalent RNA modification that plays a key role in regulating eukaryotic cellular mRNA functions. RNA m6A modification is regulated by two groups of cellular proteins, writers and erasers that add or remove m6A, respectively. HIV-1 RNA contains m6A modifications that modulate viral infection and gene expression in CD4+ T cells. However, it remains unclear whether m6A modifications of HIV-1 RNA modulate innate immune responses in myeloid cells that are important for antiviral immunity. Here we show that m6A modification of HIV-1 RNA suppresses the expression of antiviral cytokine type-I interferon (IFN-I) in differentiated human monocytic cells and primary monocyte-derived macrophages. Transfection of differentiated monocytic U937 cells with HIV-1 RNA fragments containing a single m6A-modification significantly reduced IFN-I mRNA expression relative to their unmodified RNA counterparts. We generated HIV-1 with altered m6A levels of RNA by manipulating the expression of the m6A erasers (FTO and ALKBH5) or pharmacological inhibition of m6A addition in virus-producing cells, or by treating HIV-1 RNA with recombinant FTO in vitro. HIV-1 RNA transfection or viral infection of differentiated U937 cells and primary macrophages demonstrated that HIV-1 RNA with decreased m6A levels enhanced IFN-I expression, whereas HIV-1 RNA with increased m6A modifications had opposite effects. Our mechanistic studies indicated that m6A of HIV-1 RNA escaped retinoic acid-induced gene I (RIG-I)-mediated RNA sensing and activation of the transcription factors IRF3 and IRF7 that drive IFN-I gene expression. Together, these findings suggest that m6A modifications of HIV-1 RNA evade innate immune sensing in myeloid cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984636PMC
March 2021

Modulatory Potential of LncRNA Zfas1 for Inflammation and Neuronal Apoptosis in Temporal Lobe Epilepsy.

Yonsei Med J 2021 Mar;62(3):215-223

Department of Rehabilitation Medicine, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical Univeristy, Suzhou, China.

Purpose: This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE).

Materials And Methods: Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry.

Results: Serum levels of Zfas1 were higher in TLE patients than in healthy controls (<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKβ in neurons (<0.05).

Conclusion: Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2021.62.3.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934098PMC
March 2021

Enantioselective construction of six- and seven-membered triorgano-substituted silicon-stereogenic heterocycles.

Nat Commun 2021 02 23;12(1):1249. Epub 2021 Feb 23.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, China.

The exploitation of chirality at silicon in asymmetric catalysis is one of the most intriguing and challenging tasks in synthetic chemistry. In particular, construction of enantioenriched mediem-sized silicon-stereogenic heterocycles is highly attractive, given the increasing demand for the synthesis of novel functional-materials-oriented silicon-bridged compounds. Here, we report a rhodium-catalyzed enantioselective construction of six- and seven-membered triorgano-substituted silicon-stereogenic heterocycles. This process undergoes a direct dehydrogenative C-H silylation, giving access to a wide range of triorgano-substituted silicon-stereogenic heterocycles in good to excellent yields and enantioselectivities, that significantly enlarge the chemical space of the silicon-centered chiral molecules. Further elaboration of the chiral monohydrosilane product delivers various corresponding tetraorgano-substituted silicon-stereogenic heterocycles without the loss of enantiopurity. These silicon-bridged heterocycles exhibit bright blue fluorescence, which would have potential application prospects in organic optoelectronic materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21489-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902825PMC
February 2021

Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma.

NPJ Genom Med 2021 Feb 11;6(1):11. Epub 2021 Feb 11.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41525-021-00179-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878492PMC
February 2021

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

Clin Epigenetics 2021 Feb 11;13(1):33. Epub 2021 Feb 11.

Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People's Republic of China.

Background: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response.

Methods: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort.

Results: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage.

Conclusions: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-020-00973-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879534PMC
February 2021

Electrochemical Radical Silyl-Oxygenation of Activated Alkenes.

Angew Chem Int Ed Engl 2021 Apr 8;60(16):8744-8749. Epub 2021 Mar 8.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

An efficient electrochemical radical silyl-oxygenation of electron-deficient alkenes is demonstrated, which gives access to a variety of new highly functionalized silicon-containing molecules, including β-silyl-cyanohydrin derivatives in good yields with excellent chemo- and regio-selectivity. This electrochemical radical silylation process conducts under mild conditions without the use of transition metal catalyst or chemical oxidant and exhibits a wide scope of substrate silanes with high functional-group tolerance. The ability to access silyl radicals using electrochemical Si-H activation offers new perspectives for the synthesis of valuable organosilicon compounds in a sustainable and green manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202016620DOI Listing
April 2021

Nonsegmented Negative-Sense RNA Viruses Utilize -Methyladenosine (mA) as a Common Strategy To Evade Host Innate Immunity.

J Virol 2021 04 12;95(9). Epub 2021 Apr 12.

Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA

-Methyladenosine (mA) is the most abundant internal RNA modification catalyzed by host RNA methyltransferases. As obligate intracellular parasites, many viruses acquire mA methylation in their RNAs. However, the biological functions of viral mA methylation are poorly understood. Here, we found that viral mA methylation serves as a molecular marker for host innate immunity to discriminate self from nonself RNA and that this novel biological function of viral mA methylation is universally conserved in several families in nonsegmented negative-sense (NNS) RNA viruses. Using mA methyltransferase (METTL3) knockout cells, we produced mA-deficient virion RNAs from the representative members of the families , , and and found that these mA-deficient viral RNAs triggered significantly higher levels of type I interferon compared to the mA-sufficient viral RNAs, in a RIG-I-dependent manner. Reconstitution of the RIG-I pathway revealed that mA-deficient virion RNA induced higher expression of RIG-I, bound to RIG-I more efficiently, enhanced RIG-I ubiquitination, and facilitated RIG-I conformational rearrangement and oligomerization. Furthermore, the mA binding protein YTHDF2 is essential for suppression of the type I interferon signaling pathway, including by virion RNA. Collectively, our results suggest that several families in NNS RNA viruses acquire mA in viral RNA as a common strategy to evade host innate immunity. The nonsegmented negative-sense (NNS) RNA viruses share many common replication and gene expression strategies. There are no vaccines or antiviral drugs for many of these viruses. We found that representative members of the families , , and among the NNS RNA viruses acquire mA methylation in their genome and antigenome as a means to escape recognition by host innate immunity via a RIG-I-dependent signaling pathway. Viral RNA lacking mA methylation induces a significantly higher type I interferon response than mA-sufficient viral RNA. In addition to uncovering mA methylation as a common mechanism for many NNS RNA viruses to evade host innate immunity, this study discovered a novel strategy to enhance type I interferon responses, which may have important applications in vaccine development, as robust innate immunity will likely promote the subsequent adaptive immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01939-20DOI Listing
April 2021

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific translation in epithelial cells.

Gut 2021 Feb 1. Epub 2021 Feb 1.

Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV-EHU), Leioa, Spain

Objectives: Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5'UTR of in the inflammatory environment characteristic of the coeliac intestinal epithelium.

Design: The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (mA)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD.

Results: Individuals harbouring the risk allele had higher mA methylation in the 5'UTR of RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall mA methylation in humans as well as in in vitro and in vivo models.

Conclusion: We identify a novel mA-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at mA proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2020-322566DOI Listing
February 2021

Asymmetric Synthesis of Silicon-Stereogenic Monohydrosilanes by Dehydrogenative C-H Silylation.

Org Lett 2021 Feb 1;23(4):1367-1372. Epub 2021 Feb 1.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

An asymmetric synthesis of silicon-stereogenic monohydrosilanes by rhodium-catalyzed dehydrogenative C-H silylation is developed. The process is suitable for the synthesis of various asymmetrically trisubstituted 1-benzosiloles and 1-benzosilolometallocenes in good yields with excellent chemo-, regio-, and stereocontrol. These selected silicon-stereogenic 1-benzosilole compounds exhibit bright blue fluorescence and CPL (circular polarized luminescence) signals, which could be attractive to practitioners of materials science.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c00029DOI Listing
February 2021

m A RNA methylation: from mechanisms to therapeutic potential.

Authors:
P Cody He Chuan He

EMBO J 2021 Feb 20;40(3):e105977. Epub 2021 Jan 20.

Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.

RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N -methyladenosine (m A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m A exerts its functions and discuss recent advances that underscore the multifaceted role of m A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m A regulators in disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020105977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849164PMC
February 2021

Malalignment and distal contact of short tapered stems could be associated with postoperative thigh pain in primary total hip arthroplasty.

J Orthop Surg Res 2021 Jan 19;16(1):67. Epub 2021 Jan 19.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.

Purpose: Short tapered stem placement has been extensively employed in total hip arthroplasty (THA). Suboptimal fixation tends to cause postoperative complications, such as thigh pain. However, it remains unclear whether poor seating/alignment of short tapered stems contributes to thigh pain. In this study, we retrospectively examined the factors that might be associated with thigh pain.

Methods: Medical records of 230 patients who had undergone THAs at our hospital were reviewed retrospectively. All patients received the same mediolateral (ML) short tapered femoral stems. The association between thigh pain and patients' demographics, radiographic findings, or the type of fitting of the femoral stems was investigated.

Results: In our cohort, 68 patients (27.8%) presented with thigh pain. Among 203 type I fit patients, 62 (30.5%) developed thigh pain, while only 6 out of 43 (12.2%) type II fit patients had thigh pain, with the differences being statistically significant (x = 6.706, p = 0.01). In addition, hip anteroposterior radiographs exhibited that the stem angulation (mean 2.52°), the variation in angulation (mean 1.32°), and the extent of femoral stem subsidence (mean 0.29 cm) were greater in patients with thigh pain than in their counterparts without thigh pain (all p < 0.05).

Conclusion: Malalignment and improper seating of short tapered stems could be at least one of the reasons for post-THA thigh pain. The distal contact between the stem tip and the medial femoral cortex might result in thigh pain. Our study suggested that distal implant contact should be avoided, and stem alignment should be meticulously performed in the placement of ML short tapered femoral stems for THA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-021-02215-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816452PMC
January 2021

m A deposition is regulated by PRMT1-mediated arginine methylation of METTL14 in its disordered C-terminal region.

EMBO J 2021 Mar 18;40(5):e106309. Epub 2021 Jan 18.

Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA, USA.

The N6-methyladenosine (m A) RNA modification serves crucial functions in RNA metabolism; however, the molecular mechanisms underlying the regulation of m A are not well understood. Here, we establish arginine methylation of METTL14, a component of the m A methyltransferase complex, as a novel pathway that controls m A deposition in mammalian cells. Specifically, protein arginine methyltransferase 1 (PRMT1) interacts with, and methylates the intrinsically disordered C terminus of METTL14, which promotes its interaction with RNA substrates, enhances its RNA methylation activity, and is crucial for its interaction with RNA polymerase II (RNAPII). Mouse embryonic stem cells (mESCs) expressing arginine methylation-deficient METTL14 exhibit significantly reduced global m A levels. Transcriptome-wide m A analysis identified 1,701 METTL14 arginine methylation-dependent m A sites located in 1,290 genes involved in various cellular processes, including stem cell maintenance and DNA repair. These arginine methylation-dependent m A sites are associated with enhanced translation of genes essential for the repair of DNA interstrand crosslinks; thus, METTL14 arginine methylation-deficient mESCs are hypersensitive to DNA crosslinking agents. Collectively, these findings reveal important aspects of m A regulation and new functions of arginine methylation in RNA metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020106309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917551PMC
March 2021

Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19.

bioRxiv 2021 Jan 6. Epub 2021 Jan 6.

COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP-inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.01.05.425478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805436PMC
January 2021

Epigenetic Regulation of Amyloid-beta Metabolism in Alzheimer's Disease.

Curr Med Sci 2020 Dec 11;40(6):1022-1030. Epub 2021 Jan 11.

Hubei University of Chinese Medicine, Wuhan, 430060, China.

Senile plaques (SPs) are one of the pathological features of Alzheimer's disease (AD) and they are formed by the overproduction and aggregation of amyloid-beta (Aβ) peptides derived from the abnormal cleavage of amyloid precursor protein (APP). Thus, understanding the regulatory mechanisms during Aβ metabolism is of great importance to elucidate AD pathogenesis. Recent studies have shown that epigenetic modulation-including DNA methylation, non-coding RNA alterations, and histone modifications-is of great significance in regulating Aβ metabolism. In this article, we review the aberrant epigenetic regulation of Aβ metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11596-020-2283-0DOI Listing
December 2020

A Prognostic Microenvironment-Related Immune Signature ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma.

Front Oncol 2020 7;10:580263. Epub 2020 Dec 7.

Center of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Objective: In the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature ESTIMATE (PROMISE model) for glioma.

Methods: Stromal score (SS) and immune score (IS) were calculated ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model.

Results: We obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells.

Conclusions: The PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.580263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793983PMC
December 2020