The nano-artificial periosteum made of PCL/MgO/AS-IV enhances MC3T3-E1 cell osteogenic differentiation and promotes bone defect repair via the EphB4/EphrinB2 signaling pathway.

Bone regeneration plays a pivotal role in periodontal tissue repair. With advancements in biotechnology materials, the utilization of nanotechnology offers a reliable platform for bone restoration in periodontitis. In this study, we successfully established a long-term bacterial infection model using Porphyromonas gingivalis (P. gingivalis) with MOI = 50. CCK-8 and ROS immunofluorescence results demonstrated that the combined effect of Mg2+ and AS-IV significantly enhanced cell proliferation and effectively suppressed the inflammatory response during bacterial infection. Alkaline phosphatase and alizarin red staining revealed that the synergistic action of Mg2+ and AS-IV notably promoted osteogenic differentiation of MC3T3-E1 cells under P. gingivalis-infected conditions. Considering the properties of these two biomaterials, we fabricated polycaprolactone (PCL) artificial periosteum loaded with MgO and AS-IV using an electrostatic spinning technique. The findings indicated that PCL/MgO/AS-IV artificial periosteum exhibited excellent biocompatibility and hydrophilicity, thereby substantially enhancing cellular adhesion to its surface as well as augmenting cellular value-added rate. Moreover, efficient drug release from the PCL/MgO/AS-IV artificial bone membrane conferred remarkable antimicrobial activity along with in vitro osteogenic potentiality. The in vivo experiments conducted on animals further substantiated the exceptional properties exhibited by PCL/MgO/AS-IV artificial periosteum in bone defect repair. Additionally, it was observed that PCL/MgO/AS-IV artificial periosteum could modulate EphB4-EphrinB2 signaling to enhance osteogenic differentiation under P.gingivalis-infected conditions.This exciting outcome suggests that PCL/MgO/AS-IV artificial periosteum holds great promise as a biomaterial for treating periodontal bone loss.

Analysis of the mediating effect between ehealth literacy and health self-management of undergraduate nursing students' mental health literacy.

BACKGROUND: Good health self-management positively affects the health of healthcare providers and their ability to manage their patients' health. This study explored the relationship between ehealth literacy, health self-management skills, and mental health literacy among undergraduate nursing students. Some studies have confirmed the correlation between e-health literacy and health self-management skills, while mental health literacy may be correlated with both, and this study aims to explore the relationship between the three. METHODS: A descriptive cross-sectional survey was conducted at a medical university in northwestern China among 385 Chinese undergraduate nursing students. Participants completed the General Information Questionnaire, the Adult Health Self-Management Skills Rating Scale, the Mental Health Literacy Rating Scale, and the eHealth Literacy Scale, and provided valid responses. The IBM SPSS 27.0 statistical software was used for data entry and descriptive analysis, t-test, ANOVA, and Pearson correlation analysis. The IBM Amos 26.0 was used to construct the mediation effect model, and the Bootstrap method was employed to test mediating effects. RESULTS: Mental health literacy, ehealth literacy, and health self-management skills of undergraduate nursing students were at a moderate to high level. Mental health literacy, ehealth literacy, and health self-management were positively correlated. Mental health literacy, particularly, played a partial mediating role of 31.1% ( 95% CI [0.307-1.418] ) between ehealth literacy and health self-management. CONCLUSIONS: Undergraduate nursing students' mental health literacy partially mediates the link between eHealth literacy and health self-management skills. Schools should emphasize the development of nursing students' e-health literacy and mental health literacy in order to improve their health self-management skills, which will not only bring about a better health outcome for the students, but will also benefit the health of the social population.

Silencing FHL2 inhibits bleomycin-induced pulmonary fibrosis through the TGF-ß1/Smad signaling pathway.

OBJECTIVE: This study aimed to investigate the inhibiting effects of FHL2 and Arbutin on cell fibrosis and their possible mechanisms. METHODS: The mRNA expression of FHL2 in pulmonary fibrosis tissues was analyzed by bioinformatics. TGF⁃ß1 induced fibrosis of mouse lung fibroblast (Mlg) and mouse primary pulmonary fibroblast (PPF) in rat's lung fibroblasts. FHL2 siRNA was transfected into Mlg and mouse PPF cells to inhibit FHL2. FHL2, α-smooth muscle actin (α-SMA), collagen 1 (Col I), and Fibronectin (Fn) were detected by qRT-PCR. Western blot expression levels of Smad3, p-Smad3, Smad2, and p-Smad2 proteins in cells. High-throughput drug screening for FHL2 inhibitors and the inhibitory effect of Arbutin on pulmonary fibrosis were validated in cellular and animal models of pulmonary fibrosis. RESULTS: The mRNA expression of FHL2 in lung fiber tissue was increased. Meanwhile, the decrease of FHL2 expression significantly inhibited the cellular fibrosis morphological changes of rat's lung fibroblasts (Mlgs) and primary lung fibroblasts (PPFs). The expression levels of α⁃SMA, Col I, and Fn were decreased. High-throughput screening showed that Arbutin targeted FHL2. Arbutin alleviated bleomycin (BLM)-induced pulmonary fibrosis in rats by inhibiting FHL2 and then the TGF-ß1/Smad signaling pathway. CONCLUSION: Inhibition of FHL2 can effectively reduce the fibrosis process induced by TGF⁃ß1 and bleomycin, and then inhibit the fibrosis.

Symptoms and experiences of frailty in lung cancer patients with chemotherapy: A mixed-method approach.

Objective: The aim of this study was to explore the symptoms and experiences of frailty in lung cancer patients treated with chemotherapy. Methods: Quantitative and qualitative research methods were implemented. A total of 302 patients aged > 18 years were recruited by convenience sampling method. Quantitative data were collected through the General Demographic Characteristics questionnaire, the Frailty Phenotype scale, the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Fourteen patients with a score of Frailty Phenotype scale ≥ 3 were drawn and their interviews were thematically analyzed. Results: The mean Frailty Phenotype score was (1.63±1.35), suggesting that most of the patients were in pre-frailty conditions. A total of 64 (21.2%) patients were non-frail, 168 (55.6%) patients were pre-frail, 70 (23.2%) patients were frail. The mean CFS, HADS scores, and PSQI scores were (26.86±8.93), (15.42±9.73), and (6.18±4.39), respectively. The Number of chemotherapy times was positively associated with frailty. Anxiety fatigue, depression and poor sleep quality positively correlated with frailty. The qualitative research showed four themes. Theme 1: the most reported symptoms of frailty were physical symptoms and psychological symptoms. Physical symptoms included fatigue, low physical activity, weight loss and poor sleep quality. Psychological symptoms included anxiety, depression and low social activities. Theme 2: frailty was mainly related to lung cancer and chemotherapeutic drugs, which can cause decreased appetite, constipation and altered taste. Theme 3: patients used bad coping strategies to manage the symptoms of frailty. Theme 4: the social support of patients was weak, especially regarding emotional support. Conclusion: The most frequent symptoms reported by lung cancer patients treated with chemotherapy were anxiety, fatigue, depression, low physical activity and poor sleep quality. Patients also complained of bad coping strategies and weak support. Medical staff should strengthen the management of frailty, aiming at improving the quality of life in lung cancer patients treated with chemotherapy.

mmu-microRNA-92a-3p attenuates pulmonary fibrosis by modulating Cpeb4-mediated Smad2/3 signaling pathway.

Pulmonary fibrosis (PF) is a chronic lung disorder, in which the mechanism of mmu-microRNA (miR)-92a-3p is not elucidated clearly. The present work was proposed to disclose mmu-miR-92a-3p-focused mechanism in PF with cytoplasmic polyadenylation element-binding protein 4 (Cpeb4)/Smad2/3 axis. PF was induced in mice by the intratracheal injection of bleomycin (BLM). Then, the BLM-treated mice were injected with mmu-miR-92a-3p- and/or Cpeb4-related adenovirus vectors. mmu-miR-92a-3p, Cpeb4, and Smad2/3 expression in lung tissues were examined. Alveolar cell apoptosis and collagen deposition in lung tissues and inflammatory factors in serum were observed. The interaction between mmu-miR-92a-3p and Cpeb4 was explored. Lowly expressed mmu-miR-92a-3p and highly expressed Cpeb4 and Smad2/3 were manifested in BLM-induced PF mice. BLM-induced PF mice exhibited enhanced inflammation, alveolar cell apoptosis, and collagen deposition, which would be attenuated by upregulating mmu-miR-92a-3p or downregulating Cpeb4. mmu-miR-92a-3p targeted Cpeb4. Upregulating mmu-miR-92a-3p or downregulating Cpeb4 inactivated the Smad2/3 signaling pathway in BLM-induced PF mice. It is elaborated that mmu-miR-92a-3p attenuates the process of PF by modulating Cpeb4-mediated Smad2/3 signaling pathway, renewing the molecular mechanism of PF.

Reliability and Validity of the Chinese Version of the Scale for Assessing the Stigma of Mental Illness in Nursing.

Background: The prevalence of mental illness continues to increase in China, but research on stigma is still in its infancy, and there are even fewer studies on stigma among nurses. A comprehensive, effective and reliable tool is needed to assess stigma in nursing so that it can be reduced or eliminated to improve nursing quality. This study aimed to translate a 20-item scale for assessing the stigma of mental illness in nursing into Chinese and evaluate its reliability and validity. Methods: An improved Brislin translation model was used to translate the nursing mental illness stigma assessment scale into Chinese. Content and face validity were determined by a panel of experts. A convenience sample of 501 nursing students was chosen. Confirmatory factor analysis, concurrent validity and known group comparison were used to evaluate the scale's structural validity. The reliability was evaluated based on the internal consistency reliability and 2-week retest reliability. Results: The content validity index was 0.90. Confirmatory factor analysis showed that this study supported the three-factor model. The moderate correlation between the Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing and the Perceived Devaluation Discrimination Scale suggested acceptable concurrent validity. Cronbach's α (0.863) and the retest coefficient (0.839) were indicative of internal consistency. Conclusion: The Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing has acceptable concurrent validity, marginal factor validity, and satisfactory reliability in China. Therefore, the three-factor structure of the Chinese scale should be considered. Relevance to Clinical Practice: The Chinese version of the Scale for Assessing the Stigma of Mental Illness in Nursing can be used to understand the degree of mental illness stigma in nursing.

Changes and Influencing Factors of Cognitive Impairment in Patients with Breast Cancer.

OBJECTIVE: To investigate the changes in cognitive function and its influencing factors in patients with breast cancer after chemotherapy, to provide a scientific basis for further cognitive correction therapy. METHODS: In this study, general information on age, marital status, and chemotherapy regimen was collected from 172 breast cancer chemotherapy patients. 172 patients with breast cancer undergoing chemotherapy were investigated by convenience sampling method, and the subjects were tested one-on-one using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) computer system. RESULTS: The mean value of standardized t-value of cognitive function and its abnormal dimensions in breast cancer patients undergoing chemotherapy were MCCB total cognition (66.3%, 36.99 ± 13.06, abnormal), working memory (73.3%, 36.84 ± 10.25), attention and alertness (70.3%, 37.20 ± 12.50), social cognition (65.1%, 39.54 ± 10.17), and visual memory (61.6%, 42.19 ± 9.38). A comparison of cognitive function among breast cancer chemotherapy patients with different demographic characteristics showed that differences in place of residence, educational level, monthly income, timing of chemotherapy, chemotherapy regimen, and chemotherapy times may be associated with abnormal cognitive function. Further multiple linear regression analysis was performed and the results showed that there was a linear regression between literacy, number of chemotherapy sessions, monthly personal income, and cognitive function. CONCLUSION: Cognitive impairment is common in patients with breast cancer after chemotherapy. Nurses should pay attention to the cognitive function changes and intervention of patients with breast cancer after chemotherapy, to prevent the changes of cognitive function and promote the rehabilitation of patients.

Oxidative Stress Suppresses Cellular Autophagy in Corneal Epithelium.

Purpose: Oxidative stress is a major pathogenesis of certain ocular surface diseases. This study investigated the association of oxidative stress and cellular autophagy in corneal epithelium. Methods: We applied hydrogen peroxide (H2O2) to induce oxidative damage to cultured human corneal epithelial (HCE) cells and rat corneas. Cell viability, Western blotting of caspase 8, and TUNEL staining were conducted to measure the cellular injury. The production of reactive oxygen species (ROS) was measured and the levels of the following marker and key factors of ROS were also measured to detect oxidative stress: 3-nitrotyrosine, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), superoxide dismutase, catalase, and glutathione S-transferase P. The following key factors of autophagy were measured: LC3, beclin 1, Atg 12, and P62. We also applied an agonist of autophagy, rapamycin, in the experiment. Results: Cellular injury and oxidant damage were induced after exposure to H2O2 in HCE cells and rat corneas, such as increases of cell death and production of ROS; upregulation of a ROS generation enzyme, NOX4; and downregulation of degradation factors of ROS, superoxide dismutase, catalase, and glutathione S-transferase P. However, the process of cellular autophagy was suppressed by the measurements of LC3, beclin 1, Atg 12, and P62. Furthermore, application of rapamycin antagonized the cellular and oxidant injury induced by H2O2 but increased the level of autophagy in HCE cells. Conclusions: The oxidative stress of corneal epithelium is associated with the inhibition of cellular autophagy.

SERPINA3K Ameliorates the Corneal Oxidative Injury Induced by 4-Hydroxynonenal.

Purpose: We previously demonstrated that SERPINA3K has anti-inflammatory, antiangiogenic, and antioxidant effects in corneas. Here we further investigated the effects of SERPINA3K on the corneal oxidant injury setting recently developed and induced by 4-hydroxynonenal (4-HNE). Methods: We applied the 4-HNE-induced corneal oxidant stress in cultured human corneal epithelial (HCE) cells in vitro and to the cornea of rats in vivo. The following experiments were conducted: cell counting kit 8 assay to detect cell viability; quantitative real-time PCR assay; Western blotting and immunofluorescent staining to measure gene expressions or protein levels of key reactive oxygen species (ROS)-associated factors (3-nitrotyrosine [3-NT]; nicotinamide adenine dinucleotide phosphate [NADPH]-oxidase 4 [NOX4]; superoxide dismutase [SOD]); catalase and nuclear factor [erythroid-derived 2]-like 2 [NRF2]); as well as main factors of the Wnt/ß-catenin signaling pathway (p-LRP6, ß-catenin and transcription factor 4 [TCF4]); histologic staining; and TUNEL staining to examine sections of rat corneas. Results: We found that SERPINA3K concentration dependently protected cell viability, decreased levels of ROS marker 3-NT, suppressed NOX4, and upregulated SOD and catalase. Furthermore, SERPINA3K inhibited the activation of the ROS pathway NRF2 and its downstream factors, NAD(P)H dehydrogenase (quinone) 1 (NQO1) and heme oxygenase 1 (HO1), and also suppressed the activation of the Wnt signaling pathway p-LRP6, ß-catenin, and TCF4 in HCE cells treated with 4-HNE. Meanwhile, SERPINA3K ameliorated the oxidant injury of rat corneas induced by 4-HNE and downregulated ROS systems and the Wnt/ß-catenin pathway. Conclusions: Our findings show that SERPINA3K protected the oxidant damage induced by 4-HNE in the cornea and its underlying mechanism was through suppression of the ROS system and inhibition of the activated Wnt/ß-catenin signaling pathway.

ROS-mediated Different Homeostasis of Murine Corneal Epithelial Progenitor Cell Line under Oxidative Stress.

The role of ROS in stem cell biology has not been fully illustrated and understood. Here we compared the different responses and investigated the mechanism underlying oxidative stress induced by hydrogen peroxide (H2O2) between murine corneal epithelial progenitor cell line (TKE2) and mature murine corneal epithelial cells (MCE). TKE2 showed a different homeostasis and strong resistance to H2O2. TKE2 reduced the production of ROS, inhibited ROS generation enzyme NADPH oxidase 4 (NOX4), and increased dual specificity phosphatase 6 (DUSP6). Furthermore, TKE2 activated nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway, regulated miR-125B1 and miR-29B1, and elevated levels of antioxidants glutathione S-transferase P (GSTP) and superoxide dismutases (SOD). The association with ROS of the cells was also verified by RNA interference approach and pharmacological antagonization. In addition, TKE2 enhanced the autophagy after exposure to H2O2. The novel evidence suggests that TKE2 cells have different homeostasis and strong antioxidant properties against oxidative stress via the regulation of ROS formation and pathway.

Reliability and validity of the Chinese version of the Nutritional Form For the Elderly.

OBJECTIVE: The present study aimed to translate the English version of the Nutritional Form For the Elderly into Simplified Chinese, as well as to test the reliability (homogeneity and stability) and validity (content and construct validity) of the Chinese version of the Nutritional Form For the Elderly (NUFFE-CHI). DESIGN: The study adopted a cross-sectional design. The English version of the NUFFE was translated into Simplified Chinese and a questionnaire survey was conducted. The data were analysed with statistical methods to estimate the homogeneity, stability, content and construct validity. SETTING: Jinzhou City, China. SUBJECTS: A total number of 701 community-dwelling older adults answered the questionnaire, including background variables and the NUFFE-CHI. A small group of the participants (n 50) completed the NUFFE-CHI twice for test-retest reliability. RESULTS: Cronbach's α was 0·65 and the split-half reliability was 0·67. Item-to-total correlation analyses showed that the scale has sufficient internal consistency. The test-retest reliability regarding the total scores of NUFFE-CHI was reflected in an intra-class correlation coefficient of 0·88. The intra-class correlation coefficients between the test and retest of the NUFFE-CHI items varied between 0·43 and 0·98. A content validity index of 0·83 explained good content validity. Construct validity was demonstrated in an exploratory factor analysis with a six-factor solution, explaining 57·65 % of the variance. CONCLUSIONS: This first testing of the NUFFE-CHI indicates sufficient evidence for reliability, content and construct validity. Further testing studies regarding homogeneity, concurrent validity, sensitivity and specificity are required before the NUFFE-CHI can be used as a screening instrument in clinical settings and in research.

Silencing of the glypican-3 gene affects the biological behavior of human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world. The gene glypican-3 (GPC3) is reported to be a potential therapeutic target for HCC. In this study, we use RNA interference with lentiviral vectors to explore the effect of GPC3 silencing on the biological behavior of HCC cells and the potential role of the GPC3 protein in the activation of epithelial-mesenchymal transition (EMT), which relates to HCC cell invasion and migration. Our data suggest that GPC3 silencing leads to a decrease in HCC cell proliferation and to an increase in apoptosis. We demonstrated that GPC3 silencing regulates cell invasion and migration, most probably through the activation of the EMT cellular program. In conclusion, GPC3 is associated with the HCC cell biological behavior, while the relationship between GPC3 and EMT in tumorigenesis of HCC deserves future investigation.

Stable knockdown of protein kinase CK2-alpha (CK2α) inhibits migration and invasion and induces inactivation of hedgehog signaling pathway in hepatocellular carcinoma Hep G2 cells.

Protein kinase CK2-alpha (CK2α), one isoform of the catalytic subunits of serine/threonine kinase CK2, has been indicated to participate in tumorigenesis of various malignancies, including hepatocellular carcinoma (HCC). In the present study, in order to explore the potential role of CK2α in human HCC, we employed short hairpin RNA (shRNA)-mediated RNA interference (RNAi) technology to inhibit the endogenous CK2α expression in HCC cells and established a Hep G2 cell line with stable knockdown of CK2α. Results from wound healing and transwell invasion assays indicated that stable knockdown of CK2α markedly inhibited Hep G2 cell migration and invasion as compared with those transfected with a negative control plasmid. This alteration was accompanied with expression down-regulation of matrix metalloproteinase (MMP)-2, MMP-9, Snail, Slug, Vimentin, and up-regulation of epithelial cadherin (E-cadherin). Moreover, CK2α silencing also induced inactivation of Hedgehog signaling pathway by inhibiting Gli1 and Patched homolog 1 (PTCH1) expressions in HCC cells. Collectively, these results demonstrate that knockdown of CK2α can suppress cell migration and invasion, reduces expression of MMPs, inhibits epithelial-mesenchymal transition (EMT) process and induces inactivation of Hedgehog pathway in HCC cells in vitro. Our study provides in vitro evidence to demonstrate that the pathogenesis of human HCC may be correlated with the high expression of CK2α.

Prevalence of unprotected anal intercourse among men who have sex with men in China: an updated meta-analysis.

OBJECTIVE: The purpose of this review was to assess the prevalence of unprotected anal intercourse (UAI) among men who have sex with men (MSM) in China. METHODS: A comprehensive search was conducted including online databases like "Wanfang", Chinese National Knowledge Infrastructure, PubMed and manual searches. Analyses using random-effects models were performed to estimate the prevalence of UAI among MSM in China. RESULTS: Sixty-two articles reporting eighty-two studies were selected. The pooled prevalence rates of UAI with any male partner, with regular male partners, with non-regular male partners, with casual male partners, and with commercial male partners among MSM were 53%(95%CI: 51-56%), 45%(95%CI: 39-51%), 34%(95%CI: 24-45%), 33%(95%CI: 30-36%), 12% (95%CI: 5-26%), respectively. A cumulative meta-analysis found that the pooled UAI prevalence decreased over time. CONCLUSIONS: Although the prevalence of UAI with male partners among MSM in China presents a decreasing trend over the past decade, the concomitant rise in HIV prevalence and incidence indicates that current prevention intervention efforts are insufficient to effectively contain the spread of HIV. Therefore, the persistently high prevalence of risky sexual behaviors underscores the need for innovative and effective prevention strategies among MSM.

Nicotinamide-mediated inhibition of SIRT1 deacetylase is associated with the viability of cancer cells exposed to antitumor agents and apoptosis.

Silent mating-type information regulation 2, homolog 1 (SIRT1) represents an NAD+-dependent deacetylase that regulates the processes of stress response and cell survival. However, the functions of SIRT1 in stress- and drug-induced apoptosis remain elusive. The present study was designed to determine the effects of SIRT1 in tumor cells subjected to antitumor agent treatment and to identify the underlying mechanisms during the stress response. Several of the most commonly used antitumor medications [arsenic trioxide (As2O3), Taxol and doxorubicin (doxo)] were selected to treat MCF-7 human breast cancer cells with or without nicotinamide (NAM) inhibition. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) was used to test cell viability. SIRT1 expression was tested by immunoblot analysis. The typical hallmarks of apoptosis (chromatin condensation, apoptotic bodies, sub G1 change and Annexin V+/PI- stained cells) were detected by Hoechst 33342 staining, flow cytometry and Annexin V+/PI- staining following NAM treatment. The cleavage of poly(ADP-ribose) polymerase (PARP) and caspases 9, 6 and 7 was detected through immunoblot analysis. Augmented SIRT1 expression was observed only at low concentrations (>80% cell viability) and the inhibition of SIRT1 deacetylase by NAM decreased the viability of the cancer cells exposed to low concentrations of antitumor agents. NAM induced typical apoptosis in the MCF-7 tumor cells, accompanied by the activation of the caspase cascade. SIRT1 promotes cellular survival at certain stress levels by its deacetylase function. The SIRT1 deacetylase inhibitor, NAM, triggers the activation of the caspase cascade and induces typical apoptosis in MCF-7 cells.

Recombinant mammaglobin A adenovirus-infected dendritic cells induce mammaglobin A-specific CD8+ cytotoxic T lymphocytes against breast cancer cells in vitro.

Mammaglobin A (MGBA) is a novel breast cancer-associated antigen almost exclusively over-expressed in primary and metastatic human breast cancers, making it a potential therapeutic target for breast cancer. The development of dendritic cell (DC)-induced tumor antigen specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. In this study we constructed recombinant replication-defective adenoviral (Ad) vectors encoding MGBA and evaluated their ability to trigger anti-tumor immunity in vitro. DCs were isolated from the human peripheral blood monocyte cells (PBMCs) of two HLA-A33(+) healthy female volunteers, and infected with adenovirus carrying MGBA cDNA (Ad-MGBA). After that, the Ad-MGBA-infected DCs were used to stimulate CD8(+) CTLs in vitro and the latter was used for co-culture with breast cancer cell lines. The data revealed that infection with Ad-MGBA improved DC maturation and up-regulated the expression of co-stimulatory molecules and the secretion of interleukin-12 (IL-12), but down-regulated interleukin-10 (IL-10) secretion from DCs. Ad-MGBA-infected DC-stimulated CD8(+)CTLs displayed the highest cytotoxicity towards HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells compared with other CD8(+)CTL populations, and compared with the cytotoxicity towards HLA-A33(-)/MGBA(+) breast cancer HBL-100 cells and HLA-A33(-)/MGBA(-) breast cancer MDA-MB 231 cells. In addition, Ad-MGBA-infected DC-stimulated CD8(+) CTLs showed a high level of IFNγ secretion when stimulated with HLA-A33(+)/MGBA(+) breast cancer MDA-MB-415 cells, but not when stimulated with HLA-A33(-)/MGBA(+) HBL-100 and HLA-A33(-)/MGBA(-)MDA-MB-231 cells. In addition, killing of CD8(+)CTLs against breast cancer was in a major histocompability complex (MHC)-limited pattern. Finally, the data also determined the importance of TNF-α in activating DCs and T cells. These data together suggest that MGBA recombinant adenovirus-infected DCs could induce specific anti-tumor immunity against MGBA(+) breast cancers, which could provide a novel strategy in the immunotherapy of breast cancer.

Effects of bortezomib in sensitizing human prostate cancer cell lines to NK-mediated cytotoxicity.

The proteasome inhibitor, bortezomib, has been demonstrated to sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Natural killer (NK) cells represent potent antitumor effector cells. They also express TRAIL. Therefore, we investigated whether bortezomib could sensitize tumor cells to NK cell-mediated killing, and have the same effect in human prostate cancer cell lines (LNCaP and DU145). We found that bortezomib strongly inhibits proliferation in both cell lines. Furthermore, compared with LNCaP cells, DU145 cells are more sensitive to bortezomib-induced apoptosis. However, bortezomib is unable to sensitize these two cell lines to NK cell-mediated killing in short-term assays. In long-term assays, we found that killing mediated by activated NK cells following bortezomib treatment leads to greater antitumor effects than either treatment alone. In addition, treatment with bortezomib causes these cells to upregulate apoptosis-related mRNA as well as death receptors and downregulate the major histocompatibility class (MHC)-I molecule on the cell surface of DU145 cells. In contrast, LNCaP cells are not sensitized by this treatment. Death receptors and the MHC-I molecule did not change in this cell line. These data suggest that bortezomib can be used to sensitize prostate cancer cells to NK cell-mediated killing and improve current cancer therapies. This therapeutic strategy may be more effective in patients with androgen-insensitive prostate cancer.