Physicochemical and digestive properties of corn starch nanoparticles incorporated different polyphenols.

The corn starch nanoparticles were prepared by incorporating three kinds of polyphenols, including quercetin, proanthocyanidins and tannin acid. The physicochemical and digestive properties of corn starch nanoparticles were researched. The quercetin showed a higher complexation index than proanthocyanidins and tannin acid when they complexed with corn starch. The mean size of corn starch quercetin, proanthocyanidins and tannin acid were 168.5 nm, 179.1 nm and 188.6 nm, respectively. XRD results indicated that all the corn starch-polyphenols complex showed V-type crystalline structure, the crystallinity of corn starch-quercetin complex was 19.31 %, which showed more formation of amylose-quercetin single helical formed than the other two starch-polyphenol complexes. In vitro digestion revealed that polyphenols could resist digestion and quercetin increased the content of resistant starch from 23.32 % to 35.24 % and polyphenols can form complexes with starch through hydrophobic interactions or hydrogen bonding. This study indicated the hydrophobic polyphenols had a more significant effect on the digestibility of corn starch. And the cell toxicity assessments demonstrated that all nanoparticles were nontoxic and biocompatible.

A sensitive fluorescence nanoplatform for monitoring benzoyl peroxide in food using carbon dots coupled with glutathione capped gold nanoparticles as FRET probe.

Herein, a sensitive fluorescence nanoplatform for benzoyl peroxide (BPO) detection is constructed from carbon dots (CDs) and glutathione capped gold nanoparticles (GSH-AuNPs). The fluorescence of CDs is first quenched due to the fluorescence resonance energy transfer (FRET) effect in the presence of GSH-AuNPs, and then effectively recovered when adding BPO. The detection mechanism lies in the aggregation of AuNPs in a high salt background due to oxidation of GSH caused by BPO, thus the amount of BPO is reflected by the variations of the recovered signals. The linear range and detection limit in this detection system is found to be 0.05-200 µM (R2 = 0.994) and 0.1 µg g-1 (3σ/K), respectively. Several possible interferents with high concentration show little influence on BPO detection. The proposed assay exhibits good performance for BPO determination in wheat flour and noodles, demonstrating its applicability for facile monitoring BPO additive amount in real foods.

Effectiveness of precise and quantitative rapid pulmonary rehabilitation nursing program for elderly patients with lung cancer during the perioperative period: A randomized controlled trial.

Objective: Preoperative rehabilitation should improve the functional condition of patients. Improvements in metabolism, lung mechanics, cardiovascular function, and muscle-function can be achieved by pulmonary rehabilitation. Hence, we focused on elderly patients with lung cancer undergoing surgery, and assessed the effectiveness of a rapid and precise pulmonary rehabilitation nursing program during the perioperative period. Methods: This randomized controlled trial at the department of thoracic surgery; Shanghai pulmonary hospital, China during 2021 was conducted amongst 218 elderly patients with lung cancer treated by surgical operation into either a precision quantitative nursing model nursing group (experimental group) or a perioperative routine nursing group (control group). After individual planning of the pulmonary rehabilitation nursing outpatient clinic, nurses distributed breathing trainers, instructed the patients in breathing training, and supervised the patients after the operation. For our evaluation we considered pulmonary function tests, postoperative thoracic drainage tube indwelling times, postoperative hospital stays, postoperative complication rates, and postoperative quality of life results. Result: The experimental group showed better pulmonary function, length of hospital stay, and quality of life outcomes than the control group, but the differences were not statistically significant. However, we found a significantly higher postoperative complications rate in the control group (11.9%) than in the experimental group (3.7%; p=0.02). Conclusion: Strengthening pulmonary rehabilitation nursing interventions for elderly patients with lung cancer during the perioperative period can reduce their postoperative complications and promote their rapid recovery. Clinical Trial: Registration Number - ChiCTR2100042916.].

A sandwich-type electrochemical immunosensor based on spherical nucleic acids-templated Ag nanoclusters for ultrasensitive detection of tumor biomarker.

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC4) modified Au is chosen to immobilize the secondary antibody (anti-AFP antibody 2, Ab2) through host-guest recognition between Ab2 and pSC4. When AFP is encountered, the immunoreaction signal can be significantly amplified by the electrochemical reduction of AgNCs. Under optimal circumstances, the sandwich-type electrochemical immunosensor exhibits broad limit of linearity from 0.001 to 100 ng mL-1 (R2 = 0.997) and low detection limit of 7.74 fg mL-1 (S/N = 3). The immunosensor possesses excellent repeatability and selectivity, offering a novel method for sensitive clinical diagnosis of tumor markers in human hepatocellular carcinoma.

Lanthanum ions assisted non-enzymatic ratiometric fluorescence probe for monitoring fenthion residues in agro-product samples.

In this work, a La3+ assisted glutathione-capped gold nanoclusters and carbon dots (GSH-Au NCs/CDs) nanoplatform for sensitive detection of fenthion (FEN) is fabricated. The fluorescence response of GSH-Au NCs significantly increases due to aggregation-induced emission enhancement (AIEE) effect induced by La3+, which is further enhanced with adding FEN due to the coordination between La3+ and FEN. Taking the fluorescence intensity of CDs as the signal background, the ratiometric fluorescence of GSH-Au NCs and CDs has a good linear relationship with the FEN concentration from 0.01 to 1.10 µg mL-1, and detecting FEN exhibits a good sensitivity at a low detection limit of 6.74 ng g-1. The La3+ assisted GSH-Au NCs/CDs nanoplatform demonstrates desirable selectivity and applicability for monitoring trace level of FEN in fruit and vegetable samples. The non-enzymatic strategy by taking advantage of successive AIEE of GSH-Au NCs has a great potential for facile screening organophosphate pesticides in agro-products.

Novel triterpenoids from Alisma plantago-aquatica with influence on LDL uptake in HepG2 cells by inhibiting PCSK9.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been regarded as an effective and exciting target in the treatment of atherosclerotic cardiovascular disease since 2003. Only two monoclonal antibodies have been approved in the market which, however, were also criticized for their high cost to $9000 per dose and delivery route. Exploration of natural new effective and cheaper small molecule alternatives with effective PCSK9 inhibition is feasible and desired. PURPOSE: The aim of the study was to explore natural small molecules with anti-hyperlipidemia activity through PCSK9 from Alisma plantago-aquatica. METHOD: A targeted isolation of triterpenoids from A. plantago-aquatica by LC-Orbitrap-QDa was conducted. The isolates were evaluated for their DiI-LDL uptake promoting activity with fluorescence intensity assayed in High-content Imaging System and PCSK9 inhibitory activity by Human PCSK9 Kit or western blot. The LDL uptake and PCSK9 level of target component in different concentrations and their mRNA level were further verified by corresponding kit, qPCR and western blot. RESULTS: Six novel triterpenoids, including three unusual nor-triterpenoids (1-3) and three protostane-type triterpenoids (4-6), along with thirty-four known ones, were isolated from A. plantago-aquatica. Compound 2 had the lowest number of carbon atoms than previous reported nor-PTs in this plant. The 17 triterpenoids showed relatively remarkable activities in promoting LDL uptake with relevant structure-activity relationships. And 6 triterpenoids may improve LDL uptake in HepG2 cells by inhibiting PCSK9, especially for alisol G (28) with PCSK9 inhibition reaching to 55.6%, which demonstrated to increase LDLR mRNA or protein, and simultaneously reduce PCSK9 mRNA or protein significantly. CONCLUSION: The protostane triterpenoids may serve as a new source for PCSK9 inhibitors.

Dysbiosis of the Gut Microbiome Is Associated With Histopathology of Lung Cancer.

Lung cancer is a malignancy with high incidence and mortality worldwide. Previous studies have shown that the gut microbiome plays an important role in the development and progression of metabolic cancers. However, data on the characteristics of the gut microbiome with different histopathology types of lung cancer remain scant. We collected stool samples from 28 healthy people (HP) and 61 lung cancer patients. The lung cancer patients were classified into three types according to their histopathology: Atypical Adenomatous Hyperplasia/Adenocarcinoma in situ (AAH/AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). In addition, we employed 16S rRNA gene amplicon sequencing to analyze the characteristics of the gut microbiome in these patients. Our analysis revealed that the categorized cancer patients had unique intestinal flora characteristics, and had lower density and flora diversity compared to healthy people. Besides, the structure of the flora families and genera was more complex, and each group presented specific pathogenic microbiota. The patients in the AAH/AIS group and HP group had relatively similar flora structure compared with the IA and MIA groups. In addition, we identified several flora markers that showed significant changes with the development of lung cancer. Lung cancer gut microbiota showed a decrease in short-chain fatty acids (SCFAs) producing and anti-inflammatory bacteria compared to healthy people, while some pathogenic bacteria such as proinflammatory or tumor-promoting bacteria were more abundant in lung cancer patients. On the other hand, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Group (COG) annotation demonstrated suppression of some dominant metabolism-related pathways in lung cancer. These findings provide new biomarkers for the diagnosis and prognostic assessment of lung cancer and lay the basis for novel targeted therapeutic strategies for the prevention and treatment of lung cancer. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03244605].

Silver ions involved fluorescence "on-off" responses of gold nanoclusters system for determination of carbendazim residues in fruit samples.

Herein, a fluorescence "on-off" system was developed for monitoring carbendazim (CBZ) residues in fruit samples, based on glutathione-gold nanoclusters (GSH-Au NCs) and silver ions (Ag+). First, the fluorescence intensity of GSH-Au NCs was greatly enhanced (turn on) with aggregation-induced emission enhancement (AIEE) effect in the presence of Ag+, then fluorescence quenching occurred (turn off) with adding CBZ by the chelation between CBZ and Ag+. The quenching degree was well linearly dependent on CBZ concentration covering from 0.5 to 20 µM. Moreover, the GSH-Au NCs-Ag+ system exhibited superior selectivity towards CBZ and was sensitive for the determination of CBZ in apple and orange juices with a low detection limit of 0.12 µM. The recoveries of CBZ spiked in fruit samples ranged from 81.0 % to 111.4% with the relative standard deviations less than 6.6%, demonstrating its great potential for monitoring CBZ residues in fruit samples.

COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation.

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.

Anchoring zinc-doped carbon dots on a paper-based chip for highly sensitive fluorescence detection of copper ions.

In this work, zinc-doped carbon dots (Zn-CDs) were anchored on a three-dimensional wheel type paper-based microfluidic chip, and were decorated with 6-mercaptonicotinic acid (MNA) and L-cysteine (L-Cys) for highly sensitive and rapid fluorescence detection of Cu2+. Zn-CDs were first anchored on paper through the amide bonds between the carboxyl groups of the Zn-CDs and the amino groups of the paper. Afterwards, Zn-CDs were decorated with MNA and L-Cys, effectively preventing the Zn-CDs from aggregation. The nitrogen atom on the pyridine ring and the carboxylic acid groups in MNA and L-Cys coordinated with Cu2+ to form a nonfluorescent ground-state complex, causing the fluorescence quenching of the Zn-CDs. The three-dimensional rotary design could simplify the operation process and achieve simultaneous analysis of multiple samples with different concentrations. Under optimal conditions, the fluorescent sensor exhibits linear response for the determination of Cu2+ in the range from 0.1 to 60 µg L-1 with the detection limit (LOD) of 0.018 µg L-1. The proposed strategy provides a novel way for the highly sensitive detection of Cu2+ in a complex water environment.

The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue Versus Circulating Tumor DNA in Chinese Patients With Non-Small Cell Lung Cancer.

Background: Circulating tumor DNA (ctDNA) sequence analysis shows great potential in the management of non-small cell lung cancer (NSCLC) and the prediction of drug sensitivity or resistance in many cancers. Here, we drew and compared the somatic mutational profile using ctDNA and tumor tissue sequence analysis in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), and assess its potential clinical value. Methods: In this study, 221 tumor tissues and 174 plasma samples from NSCLC patients were analyzed by hybridization capture-based next-generation sequencing (NGS) panel including 95 cancer-associated genes. Tumor response assessments were applied to 137 patients with advanced-stage (III and IV) NSCLC who first received targeted agents. Results: Twenty significantly mutated genes were identified such as TP53, EGFR, RB1, KRAS, PIK3CA, CD3EAP, CTNNB1, ERBB2, APC, BRAF, TERT, FBXW7, and HRAS. Among them, TP53 was the most frequently mutated gene and had a higher mutation probability in male (p = 0.00124) and smoking (p < 0.0001) patients. A total of 48.35% (191/395) of NSCLC patients possessed at least one actionable alteration according to the OncoKB database. Although the sensitivity of genomic profiling from ctDNA was lower than that from tumor tissue DNA, the mutational landscape of target genes from ctDNA is similar to that from tumor tissue DNA, which led to 61.22% (30/49) of mutational concordance in NSCLC. Additionally, the mutational concordance between tissue DNA and ctDNA in LUAD differs from that in LUSC, which is 63.83% versus 46.67%, indicating that NSCLC subtypes influence the specificity of mutation detection in plasma-derived ctDNA. Lastly, patients with EGFR and TP53 co-alterations showed similar responses to Gefitinib and Icotinib, and the co-occurring TP53 mutation was most likely to be a poor prognostic factor for patients receiving Gefitinib, indicating that the distributions and types of TP53 mutations may contribute to the efficacy and prognosis of molecular targeted therapy. Conclusions: As a promising alternative for tumor genomic profiling, ctDNA analysis is more credible in LUAD than in LUSC. Genomic subtyping has strong potential in prognostication and therapeutic decision-making for NSCLC patients, which indicated the necessity for the utility of target NGS in guiding clinical management.

A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice.

Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes® (MS-AOE®) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.

Comparison of Anthraquinones, Iridoid Glycosides and Triterpenoids in Morinda officinalis and Morinda citrifolia Using UPLC/Q-TOF-MS and Multivariate Statistical Analysis.

Roots of Morinda officinalis and Morinda citrifolia have been interchangeably used in traditional Chinese medicine. However, there is no experimental evidence to support this. In this study, a ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS)-based approach and a multivariate statistical analysis (MSA) were adopted to compare the difference in the chemical compounds present in the root extract of M. officinalis and M. citrifolia. There were 26 anthraquinones, 15 triterpenes, and 8 iridoid glycosides identified in the root extracts of M. officinalis, 30 anthraquinones, 1 triterpene, and 8 iridoid glycosides in the root extracts of M. citrifolia. Among these, 25 compounds presented in both plants. In addition, a principal component analysis (PCA) showed that these two herbs could be separated clearly. Furthermore, an orthogonal partial least squares-discriminant analysis (OPLS-DA) found 9 components that could be used as chemical markers to discrimination the root extracts of M. officinalis and M. citrifolia. In addition, the results of a Cell Counting Kit 8 (CCK-8) assay and cell colony formation assay indicated that methanol root extracts of M. officinalis and M. citrifolia showed no cell cytotoxicity to normal cells, even promoted the proliferation of normal liver cells. To our knowledge, this is the first time that the differences between the root extracts of M. officinalis and M. citrifolia (Hainan province) have been observed systematically at the chemistry level.

Surgery for advanced non-small cell lung cancer patient after epidermal growth factor receptor tyrosine kinase inhibitor neoadjuvant therapy.

BACKGROUND: This study aimed to evaluate the survival of the advanced non-small cell lung cancer (NSCLC) patients underwent salvage surgeries after EGFR-TKI neoadjuvant therapies. METHODS: From 2014 to 2016, 10 patients diagnosed as advanced stage NSCLC (N2 metastasis or great vessels invasion) who responded to EGFR-TKI neoadjuvant therapy were recruited in this study. All patients underwent surgeries and consented the follow-up study. RESULTS: All patients received successful radical surgeries (complete resection of the tumor with systematic lymphadenectomy). Among them, one patient passed away 7 days post-operatively due to respiratory failure. The pathology of the lesions and the lymph nodes suggested the replacement of tumors by fibrotic tissue, and concentration of focal residual tumors limited in areas of fibrous stroma and lymphocyte infiltration. Adjuvant therapy of EGFR inhibitor gefitinib for at least 6 months was applied to each patient. Each of the patients was followed up with contrasted CT scan, ultrasonography, bronchoscope and tumor markers for at least 8 months (8-30 months, median time: 24 months). The progression-free survival of these patients was 14 months since neoadjuvant therapy. CONCLUSIONS: EGFR-TKI neoadjuvant therapy is feasible and effective, along with surgery may improve the surgical rate and survival of advanced NSCLC patients. KEYWORDS: Non-small cell lung cancer (NSCLC); epidermal growth factor receptor tyrosine kinase inhibitor neoadjuvant therapy (EGFR-TKI neoadjuvant therapy); salvage surgery.

Effective immobilization of Au nanoparticles on TiO2 loaded graphene for a novel sandwich-type immunosensor.

A novel and sensitive sandwich immunosensor for amperometric determination of carcinoembryonic antigen (CEA) was designed using Au nanoparticles-titanium dioxide-graphene (AuNPs-TiO2-graphene) nanocomposites. Dopamine-functionalized graphene was firstly prepared by π-stacking interaction, and TiO2 was then attached to the surface of dopamine-graphene by the specificity and high affinity of enediol ligands to Ti (IV). Afterwards, AuNPs-TiO2-graphene nanocomposites were synthesized with photo-reduction approach under ultraviolet irradiation. The morphology and conductivity of the as-prepared nanocomposites were characterized by transmission electron microscopy, Fourier transform infrared spectra, X-ray powder diffraction, cyclic voltammetry and electrochemical impedance spectroscopy. Taking the advantage of large specific surface area and excellent biocompatibility, AuNPs could covalently link horseradish peroxidase labeled secondary antibody (HRP-Ab2) through the interaction between AuNPs and mercapto or primary amine groups of HRP-Ab2 for sandwich-type immunosensor construction. Under optimum conditions, the modified electrode exhibited a linear current response to CEA concentration in a wide range of 0.005-200ngmL-1 (R2 = 0.994) with low detection limit of 3.33pgmL-1 (S/N = 3).

Prevalence and genotype distribution of human papillomavirus infection in asymptomatic women in Liaoning province, China.

Infection by human papillomavirus (HPV) is a necessary cause of cervical cancer. The purpose of this study was to investigate the prevalence and genotype distribution of HPV infection in Chinese women who were asymptomatic for cervical diseases. Cervical cytology samples were collected from 6479 asymptomatic Chinese women of Liaoning province, and tested for various HPV genotypes using a chip hybridization assay. HPV was found in 10.3% of all the asymptomatic women studied, with the prevalence of high risk HPV (HR HPV) and low risk HPV (LR HPV) being 9.5% and 1.1%, respectively. HPV genotypes 16, 52, and 58 were found the most frequently genotypes in the HR HPV positive women, and were present in 26.2%, 19.4% and 13.8%, respectively. A graph of HR HPV positive infection rates as a function of age is U-shaped, with a peak in women less than 30 years old and a second peak among women older than 50 years. Nearly half of the women infected with either HR HPV or LR HPV presented a normal looking cervix upon visual examination. The current study demonstrates that the epidemiology of HPV infection in asymptomatic Chinese women in Liaoning province is different from that in women from other regions, even from patients with cervical lesions in the same region. These findings could be used to guide the generation and design of an HPV vaccine for this population.

Clinical and immunologic results of local hyperthermia at 44 °C for extensive genital warts in patients with diabetes mellitus.

BACKGROUND: Genital warts are more extensive and difficult to treat in patients with diabetes mellitus due to defective immune responses. PURPOSE: Our aim was to confirm the suitability of local hyperthermia for the treatment of genital warts in patients with diabetes mellitus and to investigate the immune cells in lesional areas at different time intervals after treatment. METHODS: We treated three diabetic patients with extensive genital warts by local hyperthermia at 44 °C for 30 min a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical clearance. Immunohistochemical profile was described on serial biopsies from a patient with confluent plaques. RESULTS: The warty lesions in the patients resolved in 6, 4 and 9 weeks, respectively. Immunohistochemical staining in the regressing warts revealed abundant infiltrating CD4+ T and CD8+ T lymphocytes (P < 0.01), as well as macrophages and CD1a+ dendritic cells. CONCLUSIONS: This preliminary study suggested that local hyperthermia was a safe and effective single modality in the treatment of genital warts in diabetic patients and could induce a rapid immune response in lesional skin.

Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation.

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.