Publications by authors named "Chao Lu"

719 Publications

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome.

Int Braz J Urol 2021 Jul-Aug;47(4):843-855

Department of Urology, Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.

Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment.

Materials And Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS.

Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained.

Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.1104DOI Listing
December 2020

The interplay between DNA and histone methylation: molecular mechanisms and disease implications.

EMBO Rep 2021 Apr 12:e51803. Epub 2021 Apr 12.

Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.

Methylation of cytosine in CpG dinucleotides and histone lysine and arginine residues is a chromatin modification that critically contributes to the regulation of genome integrity, replication, and accessibility. A strong correlation exists between the genome-wide distribution of DNA and histone methylation, suggesting an intimate relationship between these epigenetic marks. Indeed, accumulating literature reveals complex mechanisms underlying the molecular crosstalk between DNA and histone methylation. These in vitro and in vivo discoveries are further supported by the finding that genes encoding DNA- and histone-modifying enzymes are often mutated in overlapping human diseases. Here, we summarize recent advances in understanding how DNA and histone methylation cooperate to maintain the cellular epigenomic landscape. We will also discuss the potential implication of these insights for understanding the etiology of, and developing biomarkers and therapies for, human congenital disorders and cancers that are driven by chromatin abnormalities.
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http://dx.doi.org/10.15252/embr.202051803DOI Listing
April 2021

Clinical effect of Brisson operation modified by Y-shaped incision for treatment of concealed penis in adolescents.

J Int Med Res 2021 Apr;49(4):3000605211005951

Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.

Objective: To analyze the clinical effect of the Brisson operation modified by a Y-shaped incision in treating adolescent concealed penis.

Methods: We retrospectively analyzed clinical data of 27 adolescents with a concealed penis treated with the Brisson operation modified by a Y-shaped incision in our hospital from January 2017 to March 2020.

Results: The operation went smoothly in all 27 patients. Postoperative foreskin edema occurred in 12 patients and spontaneously resolved within 1 month postoperatively. Two patients developed postoperative retropubic infection. After administering antibiotics and symptomatic treatment, both patients' conditions improved within 1 week. All operations obtained satisfactory results. Postoperatively, when the penis was in a non-erect state, it was clearly exposed without retraction or concealment; thus, demonstrating good surgical results. The prepuce was distributed naturally without obvious accumulation of redundant preputial tissue. The penile scar resembled that after circumcision. The postoperative follow-up period was 6 months, during which no patients developed recurrence.

Conclusion: The Brisson operation modified by a Y-shaped incision is effective for treating a concealed penis in adolescent patients. This technique may relieve the pathological abnormalities and retain the penile skin's integrity to the greatest extent with minimal scarring and a satisfactory appearance.
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http://dx.doi.org/10.1177/03000605211005951DOI Listing
April 2021

Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with CPLANE1 variants.

Mol Genet Genomic Med 2021 Apr 6:e1682. Epub 2021 Apr 6.

National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, China.

Background: Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain-hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available.

Methods: In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral-facial-digital defects and was therefore classified as an oral-facial-digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings.

Results: Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C>T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in CPLANE1 (NM_023073.3).

Conclusion: This study reports that two novel CPLANE1 variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with CPLANE1 variants.
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http://dx.doi.org/10.1002/mgg3.1682DOI Listing
April 2021

Chemiluminescence Resonance Energy Transfer Efficiency and Donor-Acceptor Distance: from Qualitative to Quantitative.

Angew Chem Int Ed Engl 2021 Apr 5. Epub 2021 Apr 5.

Beijing University of Chemical Technology, State Key Laboratory of Chemical Resource Engineering, CHINA.

Since its birth in 1967, the utilization of chemiluminescence resonance energy transfer (CRET) has made substantial progress in a variety of fields for its unique features. However, the quantitative relationship between CRET efficiency and donor-acceptor distance has not yet been determined owing to the difficulty in designing the variable lengths between chemiluminescent donors and acceptors. Herein, we synthesized three kinds of tetraphenylethene (TPE)-anchored cationic surfactants with aggregation-induced emission (AIE) characteristics. For the first time, it is quantitatively demonstrated that the CRET efficiency is inversely proportional to the sixth power of distance between luminol donors and TPE acceptors. The details disclosed in this contribute have provided the solid evidence that CRET follows Förster resonance theory. Our strategy would build a promising platform to control donor-acceptor distance, allowing to the interdisciplinary applications of CRET.
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http://dx.doi.org/10.1002/anie.202102999DOI Listing
April 2021

Decreased NSG3 enhances PD-L1 expression by Erk1/2 pathway to promote pancreatic cancer progress.

Am J Cancer Res 2021 1;11(3):916-929. Epub 2021 Mar 1.

The Second Clinical Medical College, Jingzhou Central Hospital, Yangtze University Jingzhou 434020, China.

Inhibiting the functioning of PD-1/PD-L1 to activate human immune system and improve the prognosis of pancreatic cancer (PC) would provide a significant boost to handling the disease. One research found the expression level of NSG3 was reduced in pediatric pilocytic astrocytoma, so is PC and we found NSG3 could regulate the expression of PD-L1. So NSG3 could become a new target for enhancing the immune response to PC. The GEPIA website was employed to analyze the prognoses in PC patients with different NSG3 levels. Immunohistochemistry (IHC) analysis was applied to detect different levels of NSG3 in para-PC and PC tissues. Cell biological function tests () were performed and a subcutaneous nude mice tumor model () was established to verify the effect of NSG3 on PC. Immunoblotting and RT-qPCR were utilized to demonstrate the inhibiting effect of NSG3 on PD-L1 through regulating Erk1/2 phosphorylation. A subcutaneous C57BL/6 tumor mice model was established to assess the possibility of a synergistic effect of NSG3 expression and the use of an anti-PD-L1 antibody on PC. PC tissues had decreased NSG3 expression levels, which led to poor prognosis. Overexpressing NSG3 suppressed proliferation, invasion and migration capacities of PC cells. On the contrary, knocking-down NSG3 prompted PC malignancy whether or . Importantly, NSG3 prevented Erk1/2 phosphorylation to inhibit PD-L1 expression. Additionally, NSG3 and an immune checkpoint inhibitor anti-PD-1 antibody acted synergistically, which enhanced the efficacy of the inhibitor. NSG3 inhibited PD-L1 expression by suppressing Erk1/2 phosphorylation to improve the immune response to PC. NSG3 is, therefore, a potential new diagnostic and prognostic marker, particularly useful in immune checkpoint blockade therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994162PMC
March 2021

Modular Design of Membrane-Active Antibiotics: From Macromolecular Antimicrobials to Small Scorpionlike Peptidomimetics.

J Med Chem 2021 Apr 1. Epub 2021 Apr 1.

Department of Chemistry, University of South Florida, Tampa, Florida 33620, United States.

Infections caused by multidrug-resistant bacteria have emerged in recent decades, leading to escalating interest in host defense peptides (HDPs) to reverse this dangerous trend. Inspired by the modular design in bioengineering, herein we report a new class of small amphiphilic scorpionlike peptidomimetics based on this strategy. These HDP mimics show potent antimicrobial activity against both Gram-positive and Gram-negative bacteria without drug resistance but with a high therapeutic index. The membrane-compromising action mode was suggested to be their potential bactericidal mechanism. Pharmacodynamic experiments were conducted using a murine abscess model of methicillin-resistant (MRSA) infections. The lead compound showed impressive in vivo therapeutic efficacy with ∼99.998% (4.7log) reduction in skin MRSA burden, a significantly higher bactericidal efficiency than ciprofloxacin, and good biocompatibility. These results highlight the potential of these HDP mimics as novel antibiotic therapeutics.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00312DOI Listing
April 2021

Pattern recognition in distributed fiber-optic acoustic sensor using an intensity and phase stacked convolutional neural network with data augmentation.

Opt Express 2021 Feb;29(3):3269-3283

Distributed acoustic sensors (DASs) have the capability of registering faint vibrations with high spatial resolution along the sensing fiber. Advanced algorithms are important for DAS in many applications since they can help extract and classify the unique signatures of different types of vibration events. Deep convolutional neural networks (CNNs), which have powerful spectro-temporal feature learning capability, are well suited for event classification in DAS. Generally, these data-driven methods are highly dependent on the availability of large quantities of training data for learning a mapping from input to output. In this work, to fully utilize the collected information and maximize the power of CNNs, we propose a method to enlarge the useful dataset for CNNs from two aspects. First, we propose an intensity and phase stacked CNN (IP-CNN) to utilize both the intensity and phase information from a DAS with coherent detection. Second, we propose to use data augmentation to further increase the training dataset size. The influence of different data augmentation methods on the performance of the proposed CNN architecture is thoroughly investigated. The experimental results show that the proposed IP-CNN with data augmentation produces a classification accuracy of 88.2% on our DAS dataset with 1km sensing length. This indicates that the usage of both intensity and phase information together with the enlarged training dataset after data augmentation can greatly improve the classification accuracy, which is useful for DAS pattern recognition in real applications.
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http://dx.doi.org/10.1364/OE.416537DOI Listing
February 2021

MIR-301b-3p Promotes Lung Adenocarcinoma Cell Proliferation, Migration and Invasion by Targeting DLC1.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821990036

Department of Cardiothoracic Surgery, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, Zhejiang China.

Background: miR-301b-3p is reported in various human cancers for its abnormal expression, while the role and molecular mechanisms in lung adenocarcinoma (LUAD) remain unclear, and this is the focus of the present study.

Materials And Methods: TCGA database was consulted to know gene expression in LUAD tissue. CCK-8, colony formation assay and Transwell assay were applied to identify the role of target genes in regulating LUAD cell biological properties. Bioinformatics analysis plus dual-luciferase assay were performed to validate the potential connection between genes.

Results: miR-301b-3p and DLC1 were the target genes of this study and respectively differentially up-regulated and down-regulated in LUAD. Functional experiments indicated that miR-301b-3p contributed to cancer cell proliferation, migration and invasion, while this effect was reversed with overexpressed DLC1 which was identified as a direct target of and regulated by miR-301b-3p.

Conclusions: Collectively, miR-301b-3p was identified to actively function on LUAD malignant progression by suppressing DLC1 expression. This discovery provides a novel therapeutic strategy for LUAD patients, which helps improve the survival of patients.
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http://dx.doi.org/10.1177/1533033821990036DOI Listing
March 2021

Identification of novel catabolic genes involved in 17β-estradiol degradation by Novosphingobium sp. ES2-1.

Environ Microbiol 2021 Mar 22. Epub 2021 Mar 22.

Institute of Organic Contaminant Control and Soil Remediation, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, China.

Novosphingobium sp. ES2-1 is an efficient 17β-estradiol (E2)-degrading bacterium, which can convert E2 to estrone (E1), then to 4-hydroxyestrone (4-OH-E1) for subsequent oxidative cracking. In this study, the molecular bases for this process were elucidated. Two novel monooxygenase systems EstP and EstO were shown to catalyse the oxygenation of E1 and 4-OH-E1, respectively. EstP was a three-component cytochrome P450 monooxygenase system consisting of EstP1 (P450 monooxygenase), EstP2 (ferredoxin) and EstP3 (ferredoxin reductase). Ultraperformance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis revealed that EstP catalysed the 4-hydroxylation of E1 to produce 4-OH-E1. The resultant 4-OH-E1 was further oxidized by a two-component monooxygenase system EstO consisting of EstO1 (flavin-dependent monooxygenases) and EstO2 (flavin reductase). UPLC-HRMS combined with H-nuclear magnetic resonance analysis demonstrated that EstO catalysed the breakage of C9-C10 to yield a ring B-cleavage product. In addition, the oxygenase component genes estP1 and estO1 exhibited contrary inductive behaviours when exposed to different steroids, suggesting that EstP1-mediated 4-hydroxylation was E2-specific, whereas EstO1-mediated monooxygenation might be involved in the degradation of testosterone, androstenedione, progesterone and pregnenolone. This also implied that the mechanisms of the catabolism of different steroids by the same microorganism might be partially interlinked.
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http://dx.doi.org/10.1111/1462-2920.15475DOI Listing
March 2021

Analyzing knowledge entities about COVID-19 using entitymetrics.

Scientometrics 2021 Mar 12:1-19. Epub 2021 Mar 12.

Department of Information Management, Peking University, Beijing, China.

COVID-19 cases have surpassed the 109 + million markers, with deaths tallying up to 2.4 million. Tens of thousands of papers regarding COVID-19 have been published along with countless bibliometric analyses done on COVID-19 literature. Despite this, none of the analyses have focused on domain entities occurring in scientific publications. However, analysis of these bio-entities and the relations among them, a strategy called entity metrics, could offer more insights into knowledge usage and diffusion in specific cases. Thus, this paper presents an entitymetric analysis on COVID-19 literature. We construct an entity-entity co-occurrence network and employ network indicators to analyze the extracted entities. We find that ACE-2 and C-reactive protein are two very important genes and that lopinavir and ritonavir are two very important chemicals, regardless of the results from either ranking.
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http://dx.doi.org/10.1007/s11192-021-03933-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953944PMC
March 2021

CircPVT1 up-regulation attenuates steroid-induced osteonecrosis of the femoral head through regulating miR-21-5p-mediated Smad7/TGFβ signalling pathway.

J Cell Mol Med 2021 Mar 18. Epub 2021 Mar 18.

Shaanxi University of Chinese Medicine, Xi'an, China.

Steroid-induced osteonecrosis of the femoral head (SIONFH) has been a common disease following corticosteroid therapy. Presently, we aim to explore the functions of circular RNA (circ) PVT1 in SIONFH rats and the underlying mechanism. Glucocorticoid (GC) was used to treat SD rats and bone marrow-derived mesenchymal stem cells (BMSCs) to construct SIONFH model in vitro and in vivo, respectively. The pathological injury of the femoral head in the SIONFH rats was detected via haematoxylin-eosin (HE) staining and immunohistochemistry (IHC). The osteogenic differentiation, proliferation and apoptosis of BMSCs were detected. Western blot was used to detect Smad7, Bax, Bcl2 and Smad2/3. The potential targets of circPVT1 and miR-21-5p were validated through luciferase reporter gene assay and RNA pull-down assay, respectively. We found that CircPVT1 was decreased in the femoral head of SIONFH rats and GC-treated BMSCs, while miR-21-5p was markedly up-regulated. Overexpressed circPVT1 attenuated the apoptosis and cell viability inhibition of BMSCs induced by GC, while miR-21-5p up-regulation had the opposite effects. What's more, the in vivo experiments confirmed that up-regulating circPVT1 repressed osteonecrosis in SIONFH rats through repressing apoptosis. Mechanistically, circPVT1 functioned as a ceRNA of miR-21-5p, which targeted at the 3'untranslated region of Smad7. CircPVT1 enhancing Smad7 and mitigating GC activated TGFβ/Smad2/3 pathway through inhibiting miR-21-5p. In conclusion, CircPVT1 exerts protective effects against SIONFH via modulating miR-21-5p-mediated Smad7/TGFβ pathway.
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http://dx.doi.org/10.1111/jcmm.16294DOI Listing
March 2021

Two-dimensional grating coupler on an X-cut lithium niobate thin-film.

Opt Express 2021 Jan;29(2):1289-1295

A two-dimensional grating coupler for coupling light between a standard single-mode fiber and ridge waveguides on an X-cut lithium niobate thin-film is designed and demonstrated. Using circular holes for grating cells, simulated coupling losses reach -3.88 dB at 1550 nm and -5.78 dB at 1563 nm with 1-dB bandwidths of 49 nm and 45 nm for P-polarized and S-polarized light inputs, respectively. Experimentally, peak coupling losses of -5.13 dB at 1561 nm and -7.6 dB at 1568 nm are obtained for P-polarized and S-polarized light inputs, respectively, and corresponding 1 dB bandwidths are about 30 nm. An approach to improve the coupling performance of the grating coupler is also proposed using two crossing ellipses as grating cells as well as a bottom metal reflector. The coupling loss and the polarization dependent loss are decreased to around -3.4 dB and 0.44 dB, respectively.
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http://dx.doi.org/10.1364/OE.413820DOI Listing
January 2021

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity.

Bioact Mater 2021 Oct 11;6(10):3207-3217. Epub 2021 Mar 11.

College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 μg mL), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947718PMC
October 2021

Prevention and Control of Pathogens Based on Big-Data Mining and Visualization Analysis.

Front Mol Biosci 2020 25;7:626595. Epub 2021 Feb 25.

National Research Institute for Family Planning, Beijing, China.

Morbidity and mortality caused by infectious diseases rank first among all human illnesses. Many pathogenic mechanisms remain unclear, while misuse of antibiotics has led to the emergence of drug-resistant strains. Infectious diseases spread rapidly and pathogens mutate quickly, posing new threats to human health. However, with the increasing use of high-throughput screening of pathogen genomes, research based on big data mining and visualization analysis has gradually become a hot topic for studies of infectious disease prevention and control. In this paper, the framework was performed on four infectious pathogens (Fusobacterium, Streptococcus, Neisseria, and Streptococcus salivarius) through five functions: 1) genome annotation, 2) phylogeny analysis based on core genome, 3) analysis of structure differences between genomes, 4) prediction of virulence genes/factors with their pathogenic mechanisms, and 5) prediction of resistance genes/factors with their signaling pathways. The experiments were carried out from three angles: phylogeny (macro perspective), structure differences of genomes (micro perspective), and virulence and drug-resistance characteristics (prediction perspective). Therefore, the framework can not only provide evidence to support the rapid identification of new or unknown pathogens and thus plays a role in the prevention and control of infectious diseases, but also help to recommend the most appropriate strains for clinical and scientific research. This paper presented a new genome information visualization analysis process framework based on big data mining technology with the accommodation of the depth and breadth of pathogens in molecular level research.
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http://dx.doi.org/10.3389/fmolb.2020.626595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947816PMC
February 2021

Vitamin D receptor inhibits EMT via regulation of epithelial mitochondrial function in intestinal fibrosis.

J Biol Chem 2021 Mar 10:100531. Epub 2021 Mar 10.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

We previously showed that vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-to-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestinal-specific VDR-knockout (VDR) mice, and fibroblast cellular models, we showed that the expression of VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic Crohn's disease. Genetic deletion of VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with DSS or TNBS, two experimental colitis inducers. Additionally, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of VDR. Mechanistically, knocking down VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, while VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.
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http://dx.doi.org/10.1016/j.jbc.2021.100531DOI Listing
March 2021

Lateralizing the affected side of hippocampal sclerosis with quantitative high angular resolution diffusion scalars: a preliminary approach validated by diffusion spectrum imaging.

Ann Transl Med 2021 Feb;9(4):297

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

Background: Conflicts in regarding the lateralization of the seizure onset for mesial temporal lobe epilepsy (MTLE) are frequently encountered during presurgical evaluation. As a more elaborate, quantified protocol, indices of diffusion spectrum imaging (DSI) might be sensitive to evaluate the seizure involvement. However, the accuracy was less revealed. Herein, we determined the lateralizing value of the DSI indices among MTLE patients.

Methods: Eleven MTLE patients were enrolled together with 11 matched health contrasts. All the participants underwent a DSI scan and with reconstruction of the diffusion scalar, including quantitative anisotropy (QA), isotropic (ISO), and track density imaging (TDI) values. Statistics of these indices were applied to identify the differences between the healthy and ipsilateral sides, and those between the patients and the controls, with special attention to areas of the crura of fornix (FORX), the parahippocampal radiation of the cingulum (PHCR), the hippocampus (HP), parahippocampus (PHC), amygdala (AM) and entorhinal cortex (EC).

Results: Regarding lateralization, TDI of the FORX and the PHCR reached an AUC value of 0.95 and 0.93, respectively (P<0.05), and QA, ISO, TDI of the PHCR, as well as TDI of the FORX were statistically significant amongst the laterals of the patients (P<0.05). Also, the QA of the PHCR were statistically different in the patients' ipsilateral side relative to the contrasts (P<0.017). The diffusion level on different grey matter structures were significantly decreased including HP, AM and EC in GQI space (P<0.017).

Conclusions: The quantitative diffusion scalars of the DSI, especially TDI of the FORX and the PHCR, are sensitive indices to define the ipsilateral side for MTLE patients. For preliminary exploration, the use of quantitative DSI scalars may help to improve the seizure outcome by increasing the accuracy of localization and lateralization for MTLE.
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http://dx.doi.org/10.21037/atm-20-5719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944293PMC
February 2021

Value of Growth/Differentiation Factor 15 in Diagnosis and the Evaluation of Chemotherapeutic Response in Lung Cancer.

Clin Ther 2021 Mar 7. Epub 2021 Mar 7.

Department of Respiratory Medicine, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, PR China. Electronic address:

Purpose: There is a need for efficient, convenient, and inexpensive methods to accurately diagnose the clinical stage of lung cancer and evaluate the efficacy of chemotherapy in patients with lung cancer. Although growth/differentiation factor 15 (GDF)-15 has great potential as a tumor marker, supporting clinical evidence is still lacking. In this study, we aimed to analyze the relationship between serum GDF15 concentration and the clinical characteristics of patients with lung cancer, and to assess the value of GDF15 in the diagnosis and curative effect of chemotherapy.

Methods: The study comprised 160 participants in total, of whom 88 had lung cancer, 31 had pneumonia, and 41 were control subjects. Among the 88 patients with lung cancer, 64 were willing to participate in follow-up chemotherapy-related studies and meet the inclusion criteria. The serum GDF15 concentration in 288 samples (31 cases, pneumonia group samples; 41 cases, control samples; 88 cases, lung cancer group samples; 64 cases, after 1 chemotherapy cycle; and 64 cases, after 2 chemotherapy cycles) with advanced lung cancer were detected by ELISA. The possible correlations between serum GDF15 level and sex, age, height, weight, body mass index, smoking history, diabetes status, and laboratory findings (hemoglobin, prealbumin, and lactate dehydrogenase) were analyzed using parametric and nonparametric tests. Thereafter, the sensitivity of GDF15 in diagnosing lung cancer was calculated. The serum levels of GDF15, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA) 21-1 were determined in 64 patients with lung cancer, before and after chemotherapy reception. For the evaluation of the efficacy of chemotherapy, receiver operating characteristic curves were plotted.

Findings: Serum GDF15 concentration at baseline was significantly higher in the lung cancer group than were those in the pneumonia and control groups (both, P < 0.001). An increased expression of serum GDF15 was significantly correlated with diabetes, anemia, and clinical stage (tumor size, nodal involvement, and presence/absence of metastasis). After 2 cycles of chemotherapy among the 64 patients who received it, serum GDF15 concentrations were significantly different from baseline in those who had progressive disease (P = 0.003), stable disease (P < 0.001), or partial response (P = 0.039). The AUC of GDF15 was greater than those of CEA, NSE, and CYFRA 21-1 (0.851 vs 0.630, 0.720, and 0.654, respectively).

Implications: GDF15 is complementary to CEA, NSE, and CYFRA 21-1 in diagnosing lung cancer and, when used in combination, it could be of great diagnostic value and may facilitate correct predictions of the efficacy of chemotherapy. Therefore, serum GDF15 concentration is valuable in lung cancer diagnosis and in the evaluation of the efficacy of chemotherapy.
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http://dx.doi.org/10.1016/j.clinthera.2021.02.001DOI Listing
March 2021

How can the accuracy of SEEG be increased? An analysis of the accuracy of multilobe-spanning SEEG electrodes based on a frameless stereotactic robot-assisted system.

Ann Palliat Med 2021 Mar 10. Epub 2021 Mar 10.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China; China International Neuroscience Institute (CHINAINI), Beijing, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China.

Background: A frameless stereotactic robot-assisted system allows stereoelectroencephalography (SEEG) electrodes to span multiple lobes. As the angularity and length are increased, maintaining accuracy of the electrodes becomes more challenging. The goal of this study was to analyze the factors that influence the accuracy of multilobe-spanning SEEG electrodes inserted using a frameless stereotactic robot-assisted system.

Methods: A total of 322 SEEG electrodes were implanted in 39 patients with refractory epilepsy, and sixtyone multilobe-spanning SEEG electrodes were selected to analyze the factors that influenced the accuracy of implantation. The target error, entrance error, depth error, and angular error were calculated by a specialized computer program. Factors including electrode depth, angular deviation, referencing method, head holder choice, and use of a predrill procedure were analyzed to determine their effects on accuracy.

Results: Thirty-nine patients (aged 2-35 years, median: 19 years; 21 females) underwent frameless robotassisted SEEG electrode implantation. The mean distance between the intended target and actual tip location was 2.57±1.70 mm (range, 0.42-9.02 mm). The mean distance between the intended entrance point and the actual location was 2.2±1.29 mm (range, 0.70-6.13 mm). The mean length of the electrodes was 84.63±7.61 mm (range, 70.60-103.99 mm). The depth error was 1.36±1.22 mm (range, 0.03-6.69 mm), and the angular deviation was 1.64±1.12 degrees (range, 0.15-4.93 degrees). Multifactor regression analysis showed that entrance error, electrode depth, depth error, angular deviation, referencing method, and head holder choice could explain 59.5% of the electrode target error. Angular deviation, choice of registration approach and head holder and the use of a predrill procedure could explain 48.1% of the electrode entrance error. Use of a predrill procedure significantly reduced the electrode angular deviation (P<0.05).

Conclusions: Head holder choice, use of a predrill procedure and angular deviation are the primary influencing factors of the accuracy of multilobe-spanning SEEG electrode placement. The Leksell frame and a predrill procedure can be used to increase the accuracy of SEEG electrode placement.
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http://dx.doi.org/10.21037/apm-20-2123DOI Listing
March 2021

Hypoglycemic Efficacy of Rh-aFGF Variants in Treatment of Diabetes in ZDF Rats.

Front Cell Dev Biol 2021 18;9:609383. Epub 2021 Feb 18.

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Acidic fibroblast growth factor (aFGF) is a promising regulator of glucose with no adverse effects of hypoglycemia. Previous researches revealed that aFGF mediated adipose tissue remodeling and insulin sensitivity. These findings supported rh-aFGF would be used as a new candidate for the treatment of insulin resistance and type 2 diabetes. In this study, we aimed to investigate the hypoglycemic efficacy of recombinant human acidic fibroblast growth factor 135 (rh-aFGF) with low mitogenic in type 2 diabetic ZDF rats. ZDF rats were treated with rh-aFGF at a daily dosage of 0.25 and 0.50 mg/kg by tail intravenous injection for 5 weeks. The blood glucose levels, oral glucose tolerance test, insulin tolerance test, HOMA-IR for insulin resistance, serum biochemical parameters, and the histopathological changes of adipose tissue, liver and other organs were detected at designed time point. The glucose uptake activity and anti-insulin resistance effect of rh-aFGF were also detected in HepG2 cells. Results revealed that rh-aFGF exhibited a better hypoglycemic effect compared with vehicle group and without the adverse effect of hypoglycemia in ZDF rats. Compared with vehicle group, rh-aFGF significantly improved the situation of hyperglycemia and insulin resistance. Rh-aFGF decreased ALT, AST, GSP, and FFA levels noticeably compared with vehicle control group ( < 0.01 or < 0.001). After 5 weeks of treatment, high-dosage rh-aFGF could remodel adipose tissue, and has no influence on other organs. H&E staining showed that rh-aFGF reduced the size of adipocytes. In addition, rh-aFGF may improve insulin resistance partly by increasing the protein expression of p-IRS-1 (human Ser 307). As a hypoglycemic drug for long-term treatment, rh-aFGF would be a potentially safe candidate for the therapy of type 2 diabetes.
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http://dx.doi.org/10.3389/fcell.2021.609383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930327PMC
February 2021

Clinicopathological Prognostic Factors and Chemotherapeutic Outcome for Two Histopathological Types of Ampulla of Vater Adenocarcinoma.

Front Oncol 2021 18;11:616108. Epub 2021 Feb 18.

Department of Gastrointestinal-Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China.

Background: Adenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV.

Methods: We retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan-Meier estimate method and a Cox proportional hazards model.

Results: Forty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34-91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors.

Conclusions: Pancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.
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http://dx.doi.org/10.3389/fonc.2021.616108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930557PMC
February 2021

DLC1 inhibits lung adenocarcinoma cell proliferation, migration and invasion via regulating MAPK signaling pathway.

Exp Lung Res 2021 Mar 7:1-10. Epub 2021 Mar 7.

Department of Cardiothoracic Surgery, Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China.

Lung adenocarcinoma (LUAD), one of the most common cancers, is a major threat to people's health due to its high mortality, and the survival of most patients suffering LUAD remains poor. This study aimed to explore the mechanism of Deleted in Liver Cancer 1 (DLC1) as a tumor suppressor underlying the occurrence and progression of LUAD. As revealed by bioinformatics analysis and qRT-PCR, DLC1 was significantly down-regulated in LUAD tumor tissue and cells. A series of cellular experiments including CCK-8, wound healing and Transwell assays were performed to detect the effect of DLC1 on the biological function of LUAD cells. It was found that overexpressing DLC1 significantly inhibited LUAD cell proliferative, migratory and invasive abilities, while knockdown of DLC1 promoted these abilities. Gene Set Enrichment Analysis (GSEA) and dual-luciferase assay were used to explore the downstream signaling pathway of DLC1, finding that DLC1 could remarkably inhibit the activity of mitogen-activated protein kinase (MAPK) signaling pathway. Western blot implemented for MAPK signaling pathway-related proteins further identified that DLC1 restrained the activation of MAPK/ERK signaling pathway. Furthermore, rescue experiments suggested that DLC1 inhibited LUAD cell proliferation and invasion by suppressing the MAPK/ERK signaling pathway. Overall, our study discussed the DLC1-dependent mechanism involved in LUAD. We found that the up-regulation of DLC1 may inhibit the malignant progression of LUAD by suppressing MAPK signaling pathway, which supports the view that DLC1 may serve as a molecular target for the targeted therapy of LUAD patients.
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http://dx.doi.org/10.1080/01902148.2021.1885524DOI Listing
March 2021

[Finite element analysis on stress concentration improvement in patellofemoral joint by releasing lateral patellar retinaculum with stiletto needle based on the theory of Jinshugu()].

Zhongguo Gu Shang 2021 Feb;34(2):126-30

Department of Orthopaedics, Wangjing Hospital of China Academy of Chinese Medicine, Beijing 100102, China.

Objective: To study mechanism of improvement of stress concentration on patellofemoral joint by stiletto needle releasing lateral patellar retinaculum guided by the theory of Jinshugu() and based on the finite element model of knee joint. and to elucidate the biomechanical mechanism of stiletto needle releasing changing patellar trajectory and reducing patellofemoral joint pressure.

Methods: CT data of knee joint from a normal male (aged 29, heighted 171 cm, weighted 58 kg) was selected. Starting with construction of three-dimensional model of knee joint by using finite element software, the finite element model of knee joint with complete tendonand bone structures were established through several steps, such as geometric reconstruction, reverse engineering, meshing, material assignment and loading analysis. The loading condition was set as 500 N load on knee joint, and the average tensile stress of quadriceps femoris tendon was about 200 N. To simulate the release of lateral patellar retinaculum by stiletto needle at 30 and 90 position of knee flexion in finite element model separately, and to compare the improvement of stress concentration of patellofemoral joint by stiletto needle intervention under different knee flexion conditions.

Results: The peak stress of patellofemoral joint and tibiofemoral joint decreased after stiletto needle releasing of patellofemoral lateral retinaculum compared with before intervention, which was(1) knee flexion at 30 degrees:patellar cartilage decreased by 0.498 MPa (decreased 9.06%), femoral trochlea decreased by 0.886 MPa(decreased 16.27%);(2) knee flexion at 90 degrees:patellar cartilage decreased by 0.558 MPa (decreased 8.6%), femoral trochlea decreasedby 0.607 MPa (decreased 9.94%).

Conclusion: Releasing lateral patellofemoral retinaculum with stiletto needle could effectively alleviate the stress concentration of patellofemoral joint and reduce local stress peak value, which it is helpful to improve patellar trajectory and make stress distribution more uniform.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.02.006DOI Listing
February 2021

Imbalance of Th17 and Tregs in thymoma may be a pathological mechanism of myasthenia gravis.

Mol Immunol 2021 May 23;133:67-76. Epub 2021 Feb 23.

Department of Cardiothorcic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. Electronic address:

An imbalance in Th17 cells and Tregs may be an important cause of the pathogenesis of thymoma with myasthenia gravis (MG). In this study, 30 patients with simple thymoma and 30 patients with thymoma with MG were analyzed. Flow cytometry analysis of Th17 and Tregs in peripheral blood revealed that the percentages of Th17 in thymoma were lower than those in thymoma with MG, while the percentages of Tregs were higher than those in simple thymoma. Serum cytokine ELISA assays showed that IL-6 levels in simple thymoma were lower than those in MG patients. Further, Th17 and Tregs levels were detected by immunohistochemical double staining of thymoma tissue; the number of positive Th17 cells in thymoma with MG was higher than that in simple thymoma, while positive Tregs showed the opposite results. RORγt protein and mRNA expression in thymoma with MG were both higher than those in simple thymoma. FOXP3 protein and mRNA expression in the thymoma with MG group were lower than those in simple thymoma. The results of coculture of thymoma cells and CD4 + T cells showed that thymoma cells could promote the differentiation of Th17 cells and inhibit the Tregs. Overall, Th17 cells and related transcription factors and cytokines in thymoma with MG patients were higher than those in thymoma patients, whereas, Tregs showed the opposite results, the mechanism may be that thymoma can secrete IL6 and IL21. These findings indicated that imbalances in Th17/Tregs may account for the pathogeny of thymoma with MG.
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http://dx.doi.org/10.1016/j.molimm.2021.02.011DOI Listing
May 2021

Circular RNA_PDHX Promotes the Proliferation and Invasion of Prostate Cancer by Sponging MiR-378a-3p.

Front Cell Dev Biol 2020 28;8:602707. Epub 2021 Jan 28.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score ( = 0.001) and pathogenic T stage ( = 0.01) and acted as an independent prognostic factor of poor survival ( = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion and , but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.
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http://dx.doi.org/10.3389/fcell.2020.602707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901981PMC
January 2021

Chromatin dysregulation associated with NSD1 mutation in head and neck squamous cell carcinoma.

Cell Rep 2021 Feb;34(8):108769

Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill University Genome Centre, Montreal, QC H3A 0G1, Canada. Electronic address:

Chromatin dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the transcriptomic consequences of mutations in chromatin modifier genes. Recently, mutations in the histone methyltransferase gene nuclear receptor binding SET domain protein 1 (NSD1) have been identified in a subset of common and deadly head and neck squamous cell carcinomas (HNSCCs). Here, we use genome-wide approaches and genome editing to dissect the downstream effects of loss of NSD1 in HNSCC. We demonstrate that NSD1 mutations are responsible for loss of intergenic H3K36me2 domains, followed by loss of DNA methylation and gain of H3K27me3 in the affected genomic regions. In addition, those regions are enriched in cis-regulatory elements, and subsequent loss of H3K27ac correlates with reduced expression of their target genes. Our analysis identifies genes and pathways affected by the loss of NSD1 and paves the way to further understanding the interplay among chromatin modifications in cancer.
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http://dx.doi.org/10.1016/j.celrep.2021.108769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006058PMC
February 2021

Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation.

Proc Natl Acad Sci U S A 2021 Mar;118(9)

Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032;

Hotspot histone H3 mutations have emerged as drivers of oncogenesis in cancers of multiple lineages. Specifically, H3 lysine 36 to methionine (H3K36M) mutations are recurrently identified in chondroblastomas, undifferentiated sarcomas, and head and neck cancers. While the mutation reduces global levels of both H3K36 dimethylation (H3K36me2) and trimethylation (H3K36me3) by dominantly inhibiting their respective specific methyltransferases, the relative contribution of these methylation states to the chromatin and phenotypic changes associated with H3K36M remains unclear. Here, we specifically deplete H3K36me2 or H3K36me3 in mesenchymal cells, using CRISPR-Cas9 to separately knock out the corresponding methyltransferases NSD1/2 or SETD2. By profiling and comparing the epigenomic and transcriptomic landscapes of these cells with cells expressing the H3.3K36M oncohistone, we find that the loss of H3K36me2 could largely recapitulate H3.3K36M's effect on redistribution of H3K27 trimethylation (H3K27me3) and gene expression. Consistently, knockout of , but not , phenocopies the differentiation blockade and hypersensitivity to the DNA-hypomethylating agent induced by H3K36M. Together, our results support a functional divergence between H3K36me2 and H3K36me3 and their nonredundant roles in H3K36M-driven oncogenesis.
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http://dx.doi.org/10.1073/pnas.2021795118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936350PMC
March 2021

Functional interrogation of DNA damage response variants with base editing screens.

Cell 2021 Feb;184(4):1081-1097.e19

Department of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

Mutations in DNA damage response (DDR) genes endanger genome integrity and predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base editing screens, we identify > 2,000 sgRNAs that generate nucleotide variants in 86 DDR genes, resulting in altered cellular fitness upon DNA damage. Among those variants, we discover loss- and gain-of-function mutants in the Tudor domain of the DDR regulator 53BP1 that define a non-canonical surface required for binding the deubiquitinase USP28. Moreover, we characterize variants of the TRAIP ubiquitin ligase that define a domain, whose loss renders cells resistant to topoisomerase I inhibition. Finally, we identify mutations in the ATM kinase with opposing genome stability phenotypes and loss-of-function mutations in the CHK2 kinase previously categorized as variants of uncertain significance for breast cancer. We anticipate that this resource will enable the discovery of additional DDR gene functions and expedite studies of DDR variants in human disease.
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http://dx.doi.org/10.1016/j.cell.2021.01.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018281PMC
February 2021

Decoding the function of an oncogenic transcription factor: finding the first responders.

Authors:
Chao Lu

Mol Cell 2021 02;81(3):418-420

Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:

Transcription factors (TFs) are frequently altered in human diseases. Identifying the direct and immediate target genes of TFs is critical to understanding their role in pathophysiology. Stengel et al. (2020) applied chemogenetic and nascent transcriptome mapping technologies to define the core gene set regulated by AML1-ETO-an oncogenic TF fusion protein frequently found in acute myeloid leukemia (AML).
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http://dx.doi.org/10.1016/j.molcel.2021.01.008DOI Listing
February 2021

Identifying the Potential Differentially Expressed miRNAs and mRNAs in Osteonecrosis of the Femoral Head Based on Integrated Analysis.

Clin Interv Aging 2021 28;16:187-202. Epub 2021 Jan 28.

Department of Osteonecrosis and Joint Reconstruction, Honghui Hospital Xian Jiao Tong University Health Science Center, Xian, Shaanxi 710068, People's Republic of China.

Purpose: Osteonecrosis of the femoral head is a common disease of the hip that leads to severe pain or joint disability. We aimed to identify potential differentially expressed miRNAs and mRNAs in osteonecrosis of the femoral head.

Methods: The data of miRNA and mRNA were firstly downloaded from the database. Secondly, the regulatory network of miRNAs-mRNAs was constructed, followed by function annotation of mRNAs. Thirdly, an in vitro experiment was applied to validate the expression of miRNAs and targeted mRNAs. Finally, GSE123568 dataset was used for electronic validation and diagnostic analysis of targeted mRNAs.

Results: Several regulatory interaction pairs between miRNA and mRNAs were identified, such as hsa-miR-378c-WNT3A/DACT1/CSF1, hsa-let-7a-5p-RCAN2/IL9R, hsa-miR-28-5p-RELA, hsa-miR-3200-5p-RELN, and hsa-miR-532-5p-CLDN18/CLDN10. Interestingly, CLDN10, CLDN18, CSF1, DACT1, IL9R, RCAN2, RELN, and WNT3A had the diagnostic value for osteonecrosis of the femoral head. Wnt signaling pathway (involved WNT3A), chemokine signaling pathway (involved RELA), focal adhesion and ECM-receptor interaction (involved RELN), cell adhesion molecules (CAMs) (involved CLDN18 and CLDN10), cytokine-cytokine receptor interaction, and hematopoietic cell lineage (involved CSF1 and IL9R) were identified.

Conclusion: The identified differentially expressed miRNAs and mRNAs may be involved in the pathology of osteonecrosis of the femoral head.
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http://dx.doi.org/10.2147/CIA.S289479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851582PMC
January 2021