Exploring relationship between emotion and probiotics with knowledge graphs.

Purpose: Researchers have identified gut microbiota that interact with brain regions associated with emotion and mood. Literature reviews of those associations rely on rigorous systematic approaches and labor-intensive investments. Here we explore how knowledge graph, a large scale semantic network consisting of entities and concepts as well as the semantic relationships among them, is incorporated into the emotion-probiotic relationship exploration work. Method: We propose an end-to-end emotion-probiotics relationship exploration method with an integrated medical knowledge graph, which incorporates the text mining output of knowledge graph, concept reasoning and evidence classification. Specifically, a knowledge graph for probiotics is built based on a text-mining analysis of PubMed, and further used to retrieve triples of relationships with reasoning logistics. Then specific relationships are annotated and evidence levels are retrieved to form a new evidence-based emotion-probiotic knowledge graph. Results: Based on the probiotics knowledge graph with 40,442,404 triples, totally 1453 PubMed articles were annotated in both the title level and abstract level, and the evidence levels were incorporated to the visualization of the explored emotion-probiotic relationships. Finally, we got 4131 evidenced emotion-probiotic associations. Conclusions: The evidence-based emotion-probiotic knowledge graph construction work demonstrates an effective reasoning based pipeline of relationship exploration. The annotated relationship associations are supposed be used to help researchers generate scientific hypotheses or create their own semantic graphs for their research interests.

Itraconazole-Induced the Activation of Adenosine 5'-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling.

Itraconazole, an effective broad-spectrum antifungal drug, has been well established for its anticancer activity in cancers including melanoma. However, details concerning its underlying mechanism in melanoma are unclear. This work investigated the function of itraconazole-induced 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα) in melanoma progression through ERK signaling. The AMPKα level in melanoma tissues and cells was assessed by RT-qPCR and western blot. Survival analysis of patients with melanoma based on the AMPKα expression level was performed according to TCGA database. Melanoma cell proliferation, migration, and invasion were examined using CCK-8, colony formation, wound healing, and Transwell assays. A xenograft tumor model was established to examine the effect of itraconazole on tumor growth in vivo. The AMPKα mRNA and protein levels were reduced in melanoma tissues and cells. A low expression of AMPKα indicated a poor prognosis. Functionally, itraconazole restrained melanoma cell proliferation, migration, and invasion by upregulating AMPKα. Itraconazole activated AMPK signaling and inhibited ERK signaling in melanoma cells. Activation of ERK signaling reversed the effect of itraconazole on cellular process in melanoma. Moreover, itraconazole-induced AMPKα inhibited melanoma tumor growth in vivo by inhibiting ERK signaling. Itraconazole-induced AMPKα inhibits the progression of melanoma by inhibition of ERK signaling.

Medical Data Mining Course Development in Postgraduate Medical Education: Web-Based Survey and Case Study.

BACKGROUND: Medical postgraduates' demand for data capabilities is growing, as biomedical research becomes more data driven, integrative, and computational. In the context of the application of big data in health and medicine, the integration of data mining skills into postgraduate medical education becomes important. OBJECTIVE: This study aimed to demonstrate the design and implementation of a medical data mining course for medical postgraduates with diverse backgrounds in a medical school. METHODS: We developed a medical data mining course called "Practical Techniques of Medical Data Mining" for postgraduate medical education and taught the course online at Peking Union Medical College (PUMC). To identify the background knowledge, programming skills, and expectations of targeted learners, we conducted a web-based questionnaire survey. After determining the instructional methods to be used in the course, three technical platforms-Rain Classroom, Tencent Meeting, and WeChat-were chosen for online teaching. A medical data mining platform called Medical Data Mining - R Programming Hub (MedHub) was developed for self-learning, which could support the development and comprehensive testing of data mining algorithms. Finally, we carried out a postcourse survey and a case study to demonstrate that our online course could accommodate a diverse group of medical students with a wide range of academic backgrounds and programming experience. RESULTS: In total, 200 postgraduates from 30 disciplines participated in the precourse survey. Based on the analysis of students' characteristics and expectations, we designed an optimized course structured into nine logical teaching units (one 4-hour unit per week for 9 weeks). The course covered basic knowledge of R programming, machine learning models, clinical data mining, and omics data mining, among other topics, as well as diversified health care analysis scenarios. Finally, this 9-week course was successfully implemented in an online format from May to July in the spring semester of 2020 at PUMC. A total of 6 faculty members and 317 students participated in the course. Postcourse survey data showed that our course was considered to be very practical (83/83, 100% indicated "very positive" or "positive"), and MedHub received the best feedback, both in function (80/83, 96% chose "satisfied") and teaching effect (80/83, 96% chose "satisfied"). The case study showed that our course was able to fill the gap between student expectations and learning outcomes. CONCLUSIONS: We developed content for a data mining course, with online instructional methods to accommodate the diversified characteristics of students. Our optimized course could improve the data mining skills of medical students with a wide range of academic backgrounds and programming experience.

Combination of Hematology Indicators and Oncological Characteristics as a New Promising Prognostic Factor in Localized Clear Cell Renal Cell Carcinoma.

PURPOSE: This study aimed to construct a predictive model for recurrence and metastasis in patients with localized clear cell renal cell carcinoma (ccRCC) based on multiple preoperative blood indexes and oncological characteristics. PATIENTS AND METHODS: Overall, 442 patients with localized ccRCC between 2013 and 2015 were included. Using least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the top three risk factors from the peripheral blood indicators were screened to construct a risk score, and a prognostic model was established. Harrell's concordance index (C-index) was applied to evaluate the predictive accuracy of the model for predicting disease-free survival (DFS) in ccRCC. RESULTS: Out of 38 blood indexes, the top three predictors were fibrinogen (FIB), C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR). The FIB-CRP-NLR (FCN) score (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.21-2.9, P = 0.005) was an independent prognostic factor in multivariate analysis. Furthermore, the FIB-CRP-NLR-T-Grade (FCNTG) risk model combining FCN score, T stage and Furhman grade achieved a higher prognostic accuracy (mean C-index, 0.728) than both the FCN score alone (mean C-index, 0.675) and the stage, size, grade, and necrosis (SSIGN) score (mean C-index, 0.686) in the validation cohort. CONCLUSION: The FCN score combining peripheral blood indicators of inflammation and coagulation is an independent prognostic marker of ccRCC. The FCNTG model, which systemically incorporates preoperative blood indexes to oncological characteristics, shows its advantages of convenience and high prediction efficiency.

Development of a four-gene prognostic model for pancreatic cancer based on transcriptome dysregulation.

We systematically developed a prognostic model for pancreatic cancer that was compatible across different transcriptomic platforms and patient cohorts. After performing quality control measures, we used seven microarray datasets and two RNA sequencing datasets to identify consistently dysregulated genes in pancreatic cancer patients. Weighted gene co-expression network analysis was performed to explore the associations between gene expression patterns and clinical features. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to construct a prognostic model. We tested the predictive power of the model by determining the area under the curve of the risk score for time-dependent survival. Most of the differentially expressed genes in pancreatic cancer were enriched in functions pertaining to the tumor immune microenvironment. The transcriptome profiles were found to be associated with overall survival, and four genes were identified as independent prognostic factors. A prognostic risk score was then proposed, which displayed moderate accuracy in the training and self-validation cohorts. Furthermore, patients in two independent microarray cohorts were successfully stratified into high- and low-risk prognostic groups. Thus, we constructed a reliable prognostic model for pancreatic cancer, which should be beneficial for clinical therapeutic decision-making.

RCorp: a resource for chemical disease semantic extraction in Chinese.

BACKGROUND: To robustly identify synergistic combinations of drugs, high-throughput screenings are desirable. It will be of great help to automatically identify the relations in the published papers with machine learning based tools. To support the chemical disease semantic relation extraction especially for chronic diseases, a chronic disease specific corpus for combination therapy discovery in Chinese (RCorp) is manually annotated. METHODS: In this study, we extracted abstracts from a Chinese medical literature server and followed the annotation framework of the BioCreative CDR corpus, with the guidelines modified to make the combination therapy related relations available. An annotation tool was incorporated to the standard annotation process. RESULTS: The resulting RCorp consists of 339 Chinese biomedical articles with 2367 annotated chemicals, 2113 diseases, 237 symptoms, 164 chemical-induce-disease relations, 163 chemical-induce-symptom relations, and 805 chemical-treat-disease relations. Each annotation includes both the mention text spans and normalized concept identifiers. The corpus gets an inter-annotator agreement score of 0.883 for chemical entities, 0.791 for disease entities which are measured by F score. And the F score for chemical-treat-disease relations gets 0.788 after unifying the entity mentions. CONCLUSIONS: We extracted and manually annotated a chronic disease specific corpus for combination therapy discovery in Chinese. The result analysis of the corpus proves its quality for the combination therapy related knowledge discovery task. Our annotated corpus would be a useful resource for the modelling of entity recognition and relation extraction tools. In the future, an evaluation based on the corpus will be held.

Imprinting disorder in donor cells is detrimental to the development of cloned embryos in pigs.

Imprinting disorder during somatic cell nuclear transfer usually leads to the abnormality of cloned animals and low cloning efficiency. However, little is known about the role of donor cell imprinting in the development of cloned embryos. Here, we demonstrated that the imprinting (H19/Igf2) in porcine fetus fibroblasts derived from the morphologically abnormal cloned fetuses (the abnormal imprinting group) was more hypomethylated, and accordingly, significantly higher H19 transcription and lower Igf2 expression occurred in comparison with those in fibroblasts derived from morphologically normal cloned fetuses (the normal imprinting group) or donor fetus fibroblasts (the control group). When these fibroblasts were used as donor cells, the abnormal imprinting group displayed an even lower imprinting methylation level, in correspondence to the significantly downregulated expression of Dnmt1, Dnmt3a and Zfp57, and a markedly reduced blastocyst rate, while the normal imprinting group took on the similar patterns of imprinting, gene expression and embryo development to the control group. When 5-aza-dC was applied to reduce the fibroblasts imprinting methylation level in the normal imprinting group, cloned embryos displayed the more severely impaired imprinting and significantly lower blastocyst rate. While the upregulated H19 transcription in the abnormal imprinting group was knocked down, the imprinting statuses were partly rescued, and the cleavage and blastocyst rates significantly increased in cloned embryos. In all, donor cell imprinting disorder reduced the developmental efficiency of cloned embryos. This work provides a new insight into understanding the molecular mechanism of donor cells regulating the cloned embryo development.

Identifying Chemical-Disease Relationship in Biomedical Text Using a Multiple Kernel Learning-Boosting Method.

Chemical-induced disease relations (CID) are crucial in various biomedical tasks. In the CID task of Biocreative V, no classifiers with multiple kernels have been developed. In this study, a multiple kernel learning-boosting (MKLB) method is proposed. Different kernel functions according to different types of features were constucted and boosted, each of which were learned with multiple kernels. Our multiple kernel learning-boosting (MKLB) method achieved a F1 score of 0.5068 without incorporating knowledge bases.

BioCreative V CDR task corpus: a resource for chemical disease relation extraction.

Community-run, formal evaluations and manually annotated text corpora are critically important for advancing biomedical text-mining research. Recently in BioCreative V, a new challenge was organized for the tasks of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. Given the nature of both tasks, a test collection is required to contain both disease/chemical annotations and relation annotations in the same set of articles. Despite previous efforts in biomedical corpus construction, none was found to be sufficient for the task. Thus, we developed our own corpus called BC5CDR during the challenge by inviting a team of Medical Subject Headings (MeSH) indexers for disease/chemical entity annotation and Comparative Toxicogenomics Database (CTD) curators for CID relation annotation. To ensure high annotation quality and productivity, detailed annotation guidelines and automatic annotation tools were provided. The resulting BC5CDR corpus consists of 1500 PubMed articles with 4409 annotated chemicals, 5818 diseases and 3116 chemical-disease interactions. Each entity annotation includes both the mention text spans and normalized concept identifiers, using MeSH as the controlled vocabulary. To ensure accuracy, the entities were first captured independently by two annotators followed by a consensus annotation: The average inter-annotator agreement (IAA) scores were 87.49% and 96.05% for the disease and chemicals, respectively, in the test set according to the Jaccard similarity coefficient. Our corpus was successfully used for the BioCreative V challenge tasks and should serve as a valuable resource for the text-mining research community.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-3-cdr/.

Characterizing Health Information for Different Target Audiences.

Different groups of audiences in health care: health professionals and health consumers, each have different information needs. Health monographs targeting different audiences are created by leveraging readers' background knowledge. The NCI's Physician Data Query (PDQ®) Cancer Information Summaries provide parallel cancer information and education resources with different target audiences. In this paper, we used targeted audience-specific cancer information PDQs to measure characteristic differences on the element level between audiences. In addition, we compared vocabulary coverage. Results show a significant difference between the professional and patient version of cancer monographs in both content organization and vocabulary. This study provides a new view to assess targeted audience-specific health information, and helps editors to improve the quality and readability of health information.

Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway.

Reactive oxygen species (ROS) can drive the de­differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent studies have demonstrated that hypoxic exposure causes HIF-1-dependent repression of E-cadherin. However, the mechanism by which ROS and/or HIF suppresses E-cadherin expression remains less clear. In the present study, we found that ROS accumulation in ovarian carcinoma cells upregulated HIF-1α expression and subsequent transcriptional induction of lysyl oxidase (LOX) which repressed E-cadherin. Loss of E-cadherin facilitated ovarian cancer (OC) cell migration in vitro and promoted tumor growth in vivo. E-cadherin immunoreactivity correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation and metastasis. Negative E-cadherin expression along with FIGO stage, tumor differentiation and metastasis significantly predicted for a lower 5-year survival rate. These findings suggest that ROS play an important role in the initiation of metastatic growth of OC cells and support a molecular pathway from ROS to aggressive transformation which involves upregulation of HIF-1α and its downstream target LOX to suppress E-cadherin expression leading to an increase in cell motility and invasiveness.

Paired immunoglobulin-like receptor B regulates platelet activation.

Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM) mice had thrombocythemia and significantly higher proportions of megakaryocytes in bone marrow. Agonist-induced aggregation and spreading on immobilized fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in platelet-rich plasma containing PIRB-TM platelets was also increased. Characterization of signaling confirmed that PIRB associated with phosphatases Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP) or on spreading. The results further revealed that the phosphorylation levels of the linker for activation of T cells, SH2 domain-containing leukocyte protein of 76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with CRP. The phosphorylation levels of FAK Y397 and integrin ß3 Y759 were also enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet α-granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2 possess an antithrombotic function by suppressing collagen receptor glycoprotein VI and integrin αIIbß3-mediated signaling.

Platelet P2Y12 is involved in murine pulmonary metastasis.

The involvement of platelets in tumor progression is well recognized. The depletion of circulating platelets or pharmacologic inhibitors of platelet activation decreases the metastatic potential of circulating tumor cells in metastasis mouse models. The platelet ADP receptor P2Y12 amplifies the initial hemostatic responses activated by a variety of platelet agonists and stabilizes platelet aggregation, playing a crucial role in granule secretion, integrin activation and thrombus formation. However, the relationship between P2Y12 and tumor progression is not clear. In our study, the Lewis Lung Carcinoma (LLC) spontaneous metastatic mouse model was used to evaluate the role of P2Y12 in metastasis. The results demonstrated that P2Y12 deficiency significantly reduced pulmonary metastasis. Further studies indicated that P2Y12 deficiency diminished the ability of LLC cells to induce platelet shape change and release of active TGFß1 by a non-contact dependent mechanism resulting in a diminished, platelet-induced EMT-like transformation of the LLC cells, and that transformation probably is a prerequisite of LLC cell metastasis. Immunohistochemical analyses indicated an obvious P2Y12 deficiency related attenuation of recruitment of VEGFR1+ bone marrow derived cell clusters, and extracellular matrix fibronectin deposition in lungs, which presumably are required for pre-metastatic niche formation. In contrast to the LLC cells, non-epithelial melanoma B16 cells induced platelet aggregation in a cell number and P2Y12-dependent manner. Also, a platelet induced EMT-like transformation of B16 cells is dependent on P2Y12. In agreement with the LLC cell model, platelet P2Y12 deficiency also results in significantly less lung metastasis in the B16 melanoma experimental metastasis model. These results demonstrate that P2Y12 is a safe drug target for anti-thrombotic therapy, and that P2Y12 may serve as a new target for inhibition of tumor metastasis.

Rig-I regulates NF-κB activity through binding to Nf-κb1 3'-UTR mRNA.

Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate antiviral responses through induction of type I IFNs and inflammatory cytokines. However, whether RIG-I interacts with host cellular RNA remains undetermined. Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf-κb1. Rig-I is required for NF-κB activity via regulating Nf-κb1 expression at posttranscriptional levels. It interacts with the multiple binding sites within 3'-UTR of Nf-κb1 mRNA. Further analyses reveal that three distinct tandem motifs enriched in the 3'-UTR fragments can be recognized by Rig-I. The 3'-UTR binding with Rig-I plays a critical role in normal translation of Nf-κb1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13) and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13 significantly reduces Nf-κb1 and 3'-UTR-mediated luciferase expression levels. These findings indicate that Rig-I functions as a positive regulator for NF-κB signaling and is involved in multiple biological processes in addition to host antivirus immunity.

Integrin αIIb-mediated PI3K/Akt activation in platelets.

Integrin αIIbß3 mediated bidirectional signaling plays a critical role in thrombosis and haemostasis. Signaling mediated by the ß3 subunit has been extensively studied, but αIIb mediated signaling has not been characterized. Previously, we reported that platelet granule secretion and TxA2 production induced by αIIb mediated outside-in signaling is negatively regulated by the ß3 cytoplasmic domain residues R(724)KEFAKFEEER(734). In this study, we identified part of the signaling pathway utilized by αIIb mediated outside-in signaling. Platelets from humans and gene deficient mice, and genetically modified CHO cells as well as a variety of kinase inhibitors were used for this work. We found that aggregation of TxA2 production and granule secretion by ß3Δ724 human platelets initiated by αIIb mediated outside-in signaling was inhibited by the Src family kinase inhibitor PP2 and the PI3K inhibitor wortmannin, respectively, but not by the MAPK inhibitor U0126. Also, PP2 and wortmannin, and the palmitoylated ß3 peptide R(724)KEFAKFEEER(734), each inhibited the phosphorylation of Akt residue Ser473 and prevented TxA2 production and storage granule secretion. Similarly, Akt phosphorylation in mouse platelets stimulated by the PAR4 agonist peptide AYPGKF was αIIbß3-dependent, and blocked by PP2, wortmannin and the palmitoylated peptide p-RKEFAKFEEER. Akt was also phosphorylated in response to mAb D3 plus Fg treatment of CHO cells in suspension expressing αIIbß3-Δ724 or αIIbß3E(724)AERKFERKFE(734), but not in cells expressing wild type αIIbß3. In summary, SFK(s) and PI3K/Akt signaling is utilized by αIIb-mediated outside-in signaling to activate platelets even in the absence of all but 8 membrane proximal residues of the ß3 cytoplasmic domain. Our results provide new insight into the signaling pathway used by αIIb-mediated outside-in signaling in platelets.

Roles of purinergic receptor P2Y, G protein-coupled 12 in the development of atherosclerosis in apolipoprotein E-deficient mice.

OBJECTIVE: The aim of the study was to evaluate the role of purinergic receptor P2Y, G protein-coupled 12 (P2Y12), an ADP receptor, in the development of atherosclerotic lesions. METHODS AND RESULTS: Apolipoprotein E-null mice were crossed with P2y12(-/-) mice to generate double knockout mice. The double knockout mice and the control apolipoprotein E-null mice were fed a high-fat diet for 20 weeks. Assessment of the atherosclerotic lesions in the control and double knockout mice demonstrated that P2Y12 deficiency caused a diminished lesion area, an increased fibrous content at the plaque site, and decreased monocyte/macrophage infiltration of the lesions. Polymerase chain reaction studies revealed that white blood cells do not express significant levels of P2Y12. Bone marrow transplantation experiments confirmed that P2Y12 expressed on platelets is a key factor responsible for atherosclerosis, but do not exclude a role of smooth muscle cell P2Y12. Supernatant fluid from activated P2y12(+/+) but not P2y12(-/-) platelets was capable of causing monocyte migration. In vitro studies showed that platelet P2Y12 deficiency suppressed platelet factor 4 secretion and P-selectin expression. Further work demonstrated that platelet P2Y12, through inhibition of the cAMP/protein kinase A pathway, critically regulates the release of platelet factor 4, and thereby affects monocyte recruitment and infiltration. CONCLUSIONS: These results demonstrate that P2Y12 modulates atherogenesis, at least in part by augmenting inflammatory cell recruitment via regulation of platelet α-granule release.

Emodin potentiates the anticancer effect of cisplatin on gallbladder cancer cells through the generation of reactive oxygen species and the inhibition of survivin expression.

Gallbladder carcinoma is known to be an aggressive malignancy and non-sensitive to routine chemotherapy; its prognosis is quite poor. In this study, we show that emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component from Chinese medicinal herbs, can enhance apoptosis of gallbladder cancer cells induced by cisplatin (CDDP) in a reactive oxygen species (ROS)-dependent manner. The expression of survivin, which is involved in the inhibition of apoptosis, was measured after drug treatment and it was found that this could be suppressed by CDDP. Co-treatment with emodin additively inhibited survivin expression in a ROS-dependent manner. Further experiments proved that emodin potentiated the antitumor effects of CDDP in vivo by downregulating the expression of survivin without causing detectable toxic effects on normal tissues.

SUMO2 and SUMO3 transcription is differentially regulated by oxidative stress in an Sp1-dependent manner.

Protein SUMOylation (SUMO is small ubiquitin-related modifier) is a dynamic process that is strictly regulated under physiological and pathological conditions. However, little is known about how various intra- or extra-cellular stimuli regulate expression levels of components in the SUMO system. SUMO isoforms SUMO2 and SUMO3 can rapidly convert to be conjugated in response to a variety of cellular stresses. Owing to the limitations of sequence homology, SUMO2 and SUMO3 cannot be differentiated between and are thus referred to as SUMO2/3. Whether these two isoforms are regulated in distinct manners has never been addressed. In the present paper we report that the expression of SUMO3, but not SUMO2, can be down-regulated at the transcription level by cellular oxidative stress. In the present study, we checked SUMO2 and SUMO3 mRNA levels in cells exposed to various doses of H2O2 and in cells bearing different levels of ROS (reactive oxygen species). We found an inverse relationship between SUMO3 transcription and ROS levels. We characterized a promoter region specific for the mouse Sumo3 gene that is bound by the redox-sensitive transcription factor Sp1 (specificity protein 1) and demonstrated oxidation of Sp1, as well as suppression of Sp1-DNA binding upon oxidative stress. This revealed for the first time that the expression of SUMO2 and SUMO3 is regulated differently by ROS. These findings may enhance our understanding about the regulation of SUMOylation and also shed light on the functions of Sp1.