The SIRT3 activator ganoderic acid D regulates airway mucin MUC5AC expression via the NRF2/GPX4 pathway.

PURPOSE: The expression of MUC5AC, a highly prevalent airway mucin, is regulated by stimulatory factors such as oxidative stress. Ganoderic acid D (GAD) activates mitochondrial deacetylase SIRT3. SIRT3 regulates mitochondrial function through deacetylation of mitochondrial proteins, thereby playing a significant role in alleviating oxidative stress-related diseases. Therefore, this study aimed to investigate the mechanisms and rationale underlying the regulation of MUC5AC expression by GAD. METHODS: Human airway epithelial cells (NCI-H292) were exposed to pyocyanin (PCN) to establish an in vitro cell model of airway mucus hypersecretion. The expression of SIRT3, MUC5AC, and NRF2 pathway proteins in cells was assessed. Cellular mitochondrial morphology and oxidative stress markers were analyzed. C57BL/6 mice were induced with Pseudomonas aeruginosa (PA) to establish an in vivo mouse model of airway mucus hypersecretion. The expression of SIRT3 and MUC5AC in the airways was examined. In addition, the differential expression of target genes in the airway epithelial tissues of patients with chronic obstructive pulmonary disease (COPD) was analyzed using publicly available databases. RESULTS: The results revealed a significant upregulation of MUC5AC expression and a significant downregulation of SIRT3 expression in relation to airway mucus hypersecretion. GAD inhibited the overexpression of MUC5AC in PCN-induced NCI-H292 cells and PA-induced mouse airways by upregulating SIRT3. GAD activated the NRF2/GPX4 pathway and inhibited PCN-induced oxidative stress and mitochondrial morphological changes in NCI-H292 cells. However, ML385 inhibited the regulatory effects of GAD on MUC5AC expression. CONCLUSION: The SIRT3 activator GAD downregulated MUC5AC expression, potentially through activation of the NRF2/GPX4 pathway. Accordingly, GAD may be a potential treatment approach for airway mucus hypersecretions.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

BACKGROUND: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported. METHODS: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression. RESULTS: Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation frequency than in MSS. CONCLUSION: The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.

Alterations of commensal microbiota are associated with pancreatic cancer.

BACKGROUND: Dysbiosis commonly occurs in pancreatic cancer, but its specific characteristics and interactions with pancreatic cancer remain obscure. MATERIALS AND METHODS: The 16S rRNA sequencing method was used to analyze multisite (oral and gut) microbiota characteristics of pancreatic cancer, chronic pancreatitis, and healthy controls. Differential analysis was used to identify the pancreatic cancer-associated genera and pathways. A random forest algorithm was adopted to establish the diagnostic models for pancreatic cancer. RESULTS: The chronic pancreatitis group exhibited the lowest microbial diversity, while no significant difference was found between the pancreatic cancer group and healthy controls group. Diagnostic models based on the characteristics of the oral (area under the curve (AUC) 0.916, 95% confidence interval (CI) 0.832-1) or gut (AUC 0.856; 95% CI 0.74, 0.972) microbiota effectively discriminate the pancreatic cancer samples in this study, suggesting saliva as a superior sample type in terms of detection efficiency and clinical compliance. Oral pathogenic genera (Granulicatella, Peptostreptococcus, Alloprevotella, Veillonella, etc.) and gut opportunistic genera (Prevotella, Bifidobacterium, Escherichia/Shigella, Peptostreptococcus, Actinomyces, etc.), were significantly enriched in pancreatic cancer. The 16S function prediction analysis revealed that inflammation, immune suppression, and barrier damage pathways were involved in the course of pancreatic cancer. CONCLUSION: This study comprehensively described the microbiota characteristics of pancreatic cancer and suggested potential microbial markers as non-invasive tools for pancreatic cancer diagnosis.

Extreme enhancement of superconductivity in epitaxial aluminum near the monolayer limit.

BCS theory has been widely successful at describing elemental bulk superconductors. Yet, as the length scales of such superconductors approach the atomic limit, dimensionality as well as the environment of the superconductor can lead to drastically different and unpredictable superconducting behavior. Here, we report a threefold enhancement of the superconducting critical temperature and gap size in ultrathin epitaxial Al films on Si(111), when approaching the 2D limit, based on high-resolution scanning tunneling microscopy/spectroscopy (STM/STS) measurements. Using spatially resolved spectroscopy, we characterize the vortex structure in the presence of a strong Zeeman field and find evidence of a paramagnetic Meissner effect originating from odd-frequency pairing contributions. These results illustrate two notable influences of reduced dimensionality on a BCS superconductor and present a platform to study BCS superconductivity in large magnetic fields.

Inflammatory cytokines and their correlations with different left ventricular geometries and functions in PHT patients.

OBJECTIVES: To investigate relationships between hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor -α (TNF-α), interleukin-17A (IL-17A), and interferon -γ (IFN-γ), with left ventricular geometry (LVG) and function in patients with primary hypertension (PHT). METHODS: A total of 396 PHT patients were assigned into four groups: Normal Geometry (NG), Concentric Remodeling (CR), Eccentric Hypertrophy (EH), and Concentric Hypertrophy (CH). The correlation between hs-CRP, TNF-α, IL-17A, IFN-γ, and clinical, biochemical parameters were analyzed by Pearson correlation analysis and Logistic regression. Receiver Operating Characteristic (ROC) curve was used to analyze the clinical values of hs-CRP, TNF-α, IL-17A, and IFN-γ for abnormal LVG prediction. RESULTS: NG, CR, EH, and CH group all presented increasingly higher levels of Hs-CRP, TNF-α, IL-17A, and IFN-γ, and the increase was the most prominent in the CH group. Pearson correlation analysis showed that hs-CRP, IL-17A, and IFN-γ were all positively correlated with LASct. Hs-CRP, TNF-α, and IL-17A were all negatively correlated with GLS, LASr, and LAScd. However, IFN-γ was only negatively correlated with GLS and LAScd. Logistic regression analysis showed that hs-CRP and IL-17A were independently correlated with CR; hs-CRP, TNF-α, IFN-γ, and IL-17A were independently correlated with EH and CH. ROC curve analysis showed that the area under the curve (AUC) of hs-CRP was 0.816. When the optimal diagnostic threshold of hs-CRP was 3.04 mg/L, the sensitivity and specificity of the abnormal LVG were 72.1% and 81.5%, respectively. CONCLUSION: In PHT patients, hs-CRP, TNF-α, IL-17A, and IFN-γ were correlated with abnormal LVG and left ventricular function, suggesting that inflammatory cytokines may be involved in the process of PHT-induced abnormal left ventricular structure and function. In addition, hs-CRP can be used as a health screening index for patients at high risk of abnormal LVG.

Manipulating the Electronic and Magnetic Properties of Coordinated Nickel Atoms in Metal-Organic Frameworks by Hydrogenation.

In the pursuit of manipulating the properties of single atoms, the surface-supported metal-organic frameworks (MOFs) provide us opportunities to individually address the electronic and magnetic properties of coordinated metal atoms by scanning tunneling microscopy. Recently, we have synthesized Ni-TPyP (TPyP = 5,10,15,20-tetra-(4-pyridyl) porphyrin) networks with dinuclear Ni centers on a Au(111) surface, in which the top-Ni atoms are sitting above the molecular plane. Here, we investigate the top-Ni atoms and their hydrogenated derivatives by low-temperature scanning tunneling microscopy and spectroscopy, and show that the electronic and magnetic states of top-Ni atoms can be manipulated by hydrogen adsorption. Specifically, by fitting the spin-flip spectra in vertical magnetic field, we find the spin state of top-Ni atoms is tuned from S = 1/2 to S = 1 by attaching one H atom and S = 3/2 by attaching two H atoms. Our work demonstrates atomic-scale control over the electronic and magnetic properties of coordinated metal atoms in a surface-supported MOF.

Risk Score Based on Two microRNAs as a Prognostic Marker of Hepatocellular Carcinoma and the Corresponding Competitive Endogenous RNA Network.

PURPOSE: Liver transplantation (LT) currently yields the best outcomes for hepatocellular carcinoma (HCC). However, tumor recurrence still occurs in some patients. Identifying markers that predict HCC recurrence after LT is an unmet medical need. METHODS: In this study, differential expression analysis was used to identify differentially expressed microRNAs (DEmiRs) between HCC and liver tissues in the The Cancer Genome Atlas database and in data from patients with recurrent or non-recurrent HCC in the GSE64989 dataset. The expression profiles of the overlap DEmiRs were used to construct an miRNA-based risk score to predict prognosis using Cox regression analysis. The target genes of the miRNAs of interest were predicted, and they were analyzed for functional enrichment. Furthermore, we used the miRNAs of interest to construct a competitive endogenous RNA (ceRNA) network of long non-coding RNAs (lncRNAs), miRs and mRNAs. RESULTS: Four up-regulated and three down-regulated miRNAs in HCC and recurrent HCC after LT were considered as candidate miRs. MiR-3200-3p and miR-3690 were selected to construct the miR-based risk score, which was found to be associated with poor overall survival and progression-free survival. Furthermore, it proved to be an independent prognostic factor after adjusting for other clinicopathological factors. The corresponding ceRNA networks of these two miRs that we constructed may help to understand their regulatory mechanisms in HCC. CONCLUSION: We propose a risk score based on miR-3200-3p and miR-3690 that may be useful as a prognostic marker to predict HCC recurrence after LT. We generated a ceRNA network involving these miRNAs, which may help reveal their regulatory roles in HCC.

Evaluation of the Alpha-Fetoprotein Model for Predicting Recurrence and Survival in Patients With Hepatitis B Virus (HBV)-Related Cirrhosis Who Received Liver Transplantation for Hepatocellular Carcinoma.

Introduction: The alpha-fetoprotein (AFP) model is superior to the Milan criteria in predicting the recurrence of hepatocellular carcinoma (HCC) after liver transplantation in European and Latin American populations. The purpose of this study was to determine the predictive value of the AFP model in Chinese hepatitis B virus (HBV)-related cirrhosis HCC patients. Methods: A total of 189 patients with HBV-related cirrhotic HCC were included. The recurrence rate and survival rate were estimated, and predictability was assessed by the Net Reclassification Improvement (NRI) method. Results: Of the 189 patients, patients with an AFP score >2 had a higher recurrence rate at 5 years (48.94 vs. 13.53%, p < 0.05) and lower survival rate (43.96 vs. 68.97%, p < 0.05). Considering patients within the Milan criteria, a higher 5-year recurrence rate and lower survival rate were observed in patients with an AFP model score >2 points compared to patients with a score of ≤ 2 points (recurrence rate: 58.75 vs. 12.98%, p < 0.05; survival rate: 28.57 vs. 67.41%, p = 0.047). NRI analysis showed that the AFP model exhibited superior predictability as compared to the Milan criteria. Conclusions: The AFP model may be used as a selection tool for Chinese HBV patients who require liver transplantation due to HCC.

Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma.

The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.

Primary pulmonary epithelioid angiosarcoma: A case report and literature review.

Primary pulmonary epithelioid angiosarcoma is an extremely rare malignancy. Herein, we report the case of an elderly Chinese patient with primary pulmonary epithelioid angiosarcoma. The 72-year-old man presented with a 1-month history of persistent hemoptysis and left chest pain and weight loss of 3 kg. A chest computed tomography (CT) scan revealed two masses (maximum size 3.0 cm × 2.0 cm and 0.8 cm × 0.5 cm) in right lower lobe. We performed a left thoracotomy for tumor resection. Pathological examination showed that there was a significant amount of hemorrhage, fibrinous exudates, degeneration, and necrosis. With immunohistochemical analysis, tumor cells had strong expression of CD34, FLI-1, vimentin. Morphological and immunohistochemical findings supported the diagnosis of epithelioid angiosarcoma.

[The diagnosis and treatment of late acute rejection after adult orthotopic liver transplantation].

OBJECTIVE: To explore the diagnosis, treatment and long-term outcome of late acute rejection (LAR) following adult orthotropic liver transplantation (OLT). METHODS: A total of 398 consecutive adult patients who underwent OLT in Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University between January 2007 and December 2012 were reviewed retrospectively. There were 48 patients (12. 1%) developed to LAR, including 43 male patients and 5 female patients, with an average age of (52 ± 13) years(18 - 70 years). The mean body mass index was (22.1 ± 4. 5) kg/m2 (15. 4 - 30. 4 kg/m2). The indications of the liver transplantation recipients included 16 cases of end-staged liver cirrhosis after hepatitis B or C(33. 3%), 14 cases with severe hepatitis (29. 2%), 9 cases of primary liver cancer(18. 5%), 5 cases of alcoholic liver cirrhosis (10. 4%), 1 case with autoimmune liver disease (2. 1%) , the other 3 cases (6. 3%). They were followed up by outpatient service, telephone and other means. Survival curves were generated with the Kaplan-Meier method and Cox proportional hazards modeling was used for predictors of mortality. Statistically significant variables found by single factor regression analysis were put into the Cox proportional hazards regression model of multivariate analysis. RESULTS: The time-to-event was 23. 6 months after OLT which were more common in the first year to the third year post-transplant (26/48,52. 4%). Thirty-five cases were assessed as mild, 11 cases were assessed as moderate, and 2 cases were assessed as severe ,based on the Banff schema. After adjustment to the immunosuppressive regimen, the overall recovery rate reached to 81. 3%. The rate of steroid-resistant acute rejection was 11. 8% (4/34). Inadequate immunosuppression and steroid pulsation were two independent risk factors affecting the prognosis of LAR (P = 0. 008, P = 0. 003, respectively). CONCLUSIONS: LAR is an uncommon complication after OLT. Inadequate immunosuppression and steroid pulsation are the major risk factors for prognosis of LAR. Improving patient compliance and strengthening blood concentration surveillance can increase the patient survival.

Single-crystal-conjugated polymers with extremely high electron sensitivity through template-assisted in situ polymerization.

Single-crystal-conjugated polymer (SCCP) arrays are prepared successfully via a simple method, which is a combination of the contact thermochemical reaction and solvent-free in situ polymerization. The dramatic X-ray diffraction and selective-area electron diffraction results show the high crystallinity of the SCCP arrays. These SCCP arrays display unique physical properties and show great potential in flexible electronics.

Total alkaloids of Tripterygium hypoglaucum (levl.) Hutch inhibits tumor growth both in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (levl.) Hutch (Celastraceae) (THH) root is a traditional Chinese medicinal herb commonly used for treating autoimmune diseases and cancer. Alkaloid is one of the most bioactive components of THH extract. To evaluate the in vitro and in vivo antitumor properties of the total alkaloids of THH (THHta). MATERIALS AND METHODS: THHta was extracted in pilot-scale. HCT116 cells were chose to establish human colon cancer xenograft model. The in vitro anti-tumor activity of THHta was tested by Cell malignant transformation test, Soft agar colony formation assay and MTT assay. The in vivo anti-tumor effect of THHta was confirmed by xenograft mouse model. THHta-induced apoptosis was examined by flow cytometry. The levels of apoptosis-related proteins were investigated by Western blot. RESULTS: TPA-induced cell transformation was significantly inhibited by THHta in JB6 Cl41 cells. THHta inhibits the growth of colon cancer cells in vitro in a significant dose-dependent manner. Compared to the control set, i.p. administration of THHta to xenograft mice significantly reduced both tumor weight and volume. Apoptosis induction of THHta was mediated by activation of caspase-3, PARP and inhibiting of Bcl-2, Bcl-xL and XIAP. CONCLUSION: THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent.

A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation.

Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

Crystalline structural intermediates of a breathing metal-organic framework that functions as a luminescent sensor and gas reservoir.

A rod-packing, breathing MOF (1), with two crystalline structural intermediates (1 a and 1 b; H(2) btca = benzotriazole-5-carboxylic acid) has been investigated. An underlying net approach for analyzing possible breathing MOFs, and a set of geometric parameters that can quantitatively describe such a breathing structural feature, are suggested. The 3D luminescent MOF is a promising candidate for specific sensors with exceptional sorption capacity.

High-spin versus spin-crossover versus low-spin: geometry intervention in cooperativity in a 3D polymorphic iron(II)-tetrazole MOFs system.

Reported here are three 3D metal-organic framework (MOF) polymorphs with the chemical formula [Fe(2)(H(0.67)bdt)(3)]·xH(2)O (H(2)bdt = 5,5'-(1,4-phenylene)bis(1H-tetrazole)), all of which are constructed from similar Fe(II)-tetrazole rod secondary building units (SBUs) via covalent links, but exhibit diverse spin states regulated by inter-chain cooperativity.

1,4-Diselenophene-1,4-diketone triggers caspase-dependent apoptosis in human melanoma A375 cells through induction of mitochondrial dysfunction.

Epidemiological, preclinical and clinical studies have supported the role of selenocompounds as potential cancer chemopreventive and chemotherapeutic agents. In this study, a novel selenophene-based compound, 1,4-diselenophene-1,4-diketone (DSeD), has been synthesized by Double Friedel-Crafts reaction and identified as a potent antiproliferative agent against a panel of six human caner cell lines. Despite this potency, DSeD was relatively nontoxic toward human normal cells, HS68 fibroblasts and HK-2 kidney cells. These results suggest that DSeD possesses great selectivity between cancer and normal cells. Induction of apoptosis in human melanoma A375 cells by DSeD was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Activation of caspase-9 and depletion of mitochondrial membrane potential indicated the initiation of the mitochondria-mediated apoptosis pathway. Pretreatment of cells with general caspase inhibitor z-VAD-fmk and caspase-9 inhibitor z-LEHD-fmk significantly suppressed the cell apoptosis, demonstrating the important roles of caspase and mitochondria in DSeD-induced apoptotic cell death. Furthermore, DSeD-induced apoptosis was found independent of reactive oxygen species generation. Taken together, our results suggest that DSeD induces caspase-dependent apoptosis in A375 cells through activation of mitochondria-mediated apoptosis pathway.

[Effect of celecoxib and adriamycin on proliferation and apoptosis of Raji cells and its mechanism].

OBJECTIVE: To assess the effect of celecoxib in combination with adriamycin(ADM) on cell proliferation and apoptosis. METHODS: Cell lines were treated with celecoxib,and cell proliferation was examined by the method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) at different time. The cellular apoptotic rate was analyzed by flow cytometry. RT-PCR was applied to distinguish the level of caspase-9 mRNA expression. Immunohistochemistry was used to detect the caspase-9 protein expression in Raji cells. RESULTS: Celecoxib inhibited the proliferation and increased the apoptosis of Raji cell lines in a dose-dependent and time-dependent manner within 20-100 µmol/L. Compared with the celecoxib alone, the proliferation of Raji cell lines incubated with celecoxib and adriamycin was decreased. Caspase-9 mRNA and protein expression in Raji cells were significantly enhanced after the treatment of celecoxib (P<0.05). CONCLUSION: Celecoxib can inhibit the proliferation of Raji cells in a dose-dependent and time-dependent manner. Celecoxib may lead to the apoptosis of Raji cells by up-regulating activities of caspase-9. Adriamycin could intensify the effect.

[Effect of arsenic trioxide combined with adriamycin on the proliferation and apoptosis of human lymphoma cells].

OBJECTIVE: To determine the effect of arsenic trioxide combined with adriamycin(ADM) on the proliferation and apoptosis of human lymphoma cells. METHODS: Raji cells were divided into an experimental group and a control group, and the experimental group was further divided into 1 micromol/L As(2)O(3) group,2 micromol/L As(2)O(3) group, ADM group,1 micromol/L As(2)O(3) and ADM group,2 micromol/L As(2)O(3) and ADM group. Human lymphoma cells Raji were treated with As(2)O(3) combined with ADM. Wright-Giemsa dying assay was used to observe the apoptosis morphology of lymphoma cells. The proliferation of the cells treated with As(2)O(3) and adriamycin was detected by the method of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT). Flow cytometry(FCM) was used to detect the apoptosis rate of lymphoma and the fluorescene density in the lymphocytes. Effect of arsenic trioxide and adriamycin on the mutant p53 expression in Raji cells was detected by semi-quantitive RT-PCR. RESULTS: Evident apoptotic morphological changes of Raji cells were observed 24 hours after treatment with As(2)O(3) or ADM. Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the inhibition ratio significantly (P<0.05), and the inhibition rate was related to the concentration and action time of As(2)O(3) (P<0.05). Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the apoptosis rate of lymphoma cells with obvious difference (P<0.05). Semi-quantitive and RT-PCR showed that the expression of mutant p53 in As(2)O(3) and ADM alone and combined groups was obviously less than that in the control (P<0.05). After the treatment with 1 micromol/L and 2 micromol/L As(2)O(3), the fluorescene density in the Raji cells was 18.53 and 18.12, 0.056 and 0.023 times increase respectively.There was no difference (P>0.05). CONCLUSION: As(2)O(3) and ADM alone or combined can inhibit the proliferation, induce cell apoptosis, and downregulate the expression of mutant p53 in vitro. As(2)O(3) combined with ADM has synergistic anti-lymphoma cell effect in vitro. As(2)O(3) has no significant effect on the concentration of ADM on the Raji cells, but can enhance the chemosensitivity of Raji cells, and its mechanism may be that it can downregulate the expression of mutant p53.

[Apoptosis of Burkitt's lymphoma Raji cell line induced by bortezomib].

The aim of this study was to clarify whether bortezomib might induce apoptosis in Burkitt's lymphoma Raji cell line and its mechanism. Different concentrations of bortezomib were used to treat Raji cells and its effects of time and dose were observed. Cell morphology was observed under light microscope; flow cytometry was used to analyze cell apoptosis; RT-PCR was used to detect the expressions of NF-kappaB and p53 gene mRNAs. The results showed that the bortezomib could inhibit Raji cell growth within a certain range of treating time and dose. Apoptosis were induced in relation to time and dose. The expression of NF-kappaB mRNA and p53 mRNA decreased after treatment with bortezomib. It is concluded that the bortezomib can induce Raji cell apoptosis, which provides a theoretical basis for clinical treatment. NF-kappaB and p53 gene are supposed to participate in the bortezomib induced apoptosis of Raji cells.