Effect of e-learning program for improving nurse knowledge and practice towards managing pressure injuries: A systematic review and meta-analysis.

AIM: The aim of this review was to determine the effectiveness of the e-learning programs for improving the knowledge and professional practices of nursing personnel in managing pressure injuries patients. DESIGN: Systematic review and meta-analysis. METHODS: Systematic search was done in EMBASE, SCOPUS, Cochrane library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov databases until August 2022. Meta-analysis was carried out using random-effects model, and the results were reported as pooled standardized mean differences (SMD), or odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: Eight studies were included in the analysis. Most of the studies had higher risk of bias. The pooled SMD for knowledge score and for the classification skill were 1.40 (95%CI: 0.45-2.35; I2 = 93.1%) and 1.75 (95%CI: 0.94-3.24; I2 = 78.3%) respectively. The pooled OR for the classification skills was 1.75 (95%CI: 0.94-3.24; I2 = 78.3%). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Harmonizing Thickness and Permeability in Bone Tissue Engineering: A Novel Silk Fibroin Membrane Inspired by Spider Silk Dynamics.

Guided bone regeneration gathers significant interest in the realm of bone tissue engineering; however, the interplay between membrane thickness and permeability continues to pose a challenge that can be addressed by the water-collecting mechanism of spider silk, where water droplets efficiently move from smooth filaments to rough conical nodules. Inspired by the natural design of spider silk, an innovative silk fibroin membrane is developed featuring directional fluid transportation via harmoniously integrating a smooth, dense layer with a rough, loose layer; conical microchannels are engineered in the smooth and compact layer. Consequently, double-layered membranes with cone-shaped microporous passageways (CSMP-DSF membrane) are designed for in situ bone repair. Through extensive in vitro testing, it is noted that the CSMP-DSF membrane guides liquid flow from the compact layer's surface to the loose layer, enabling rapid diffusion. Remarkably, the CSMP-DSF membrane demonstrates superior mechanical properties and resistance to bacterial adhesion. When applied in vivo, the CSMP-DSF membrane achieves results on par with the commercial Bio-Gide collagen membranes. This innovative integration of a cross-thickness wetting gradient structure offers a novel solution, harmonizing the often-conflicting requirements of material transport, mechanical strength, and barrier effectiveness, while also addressing issues related to tissue engineering scaffold perfusion.

Assessing measurement invariance of the SEGUE framework among Chinese and Ghanaian patients: A cross-sectional study.

Objective: Measurement invariance assesses the psychometric equivalence of a construct across groups or across time. This study aimed to find out whether the newly modified 5-point Likert scale SEGUE Framework for evaluating doctor's communication skills demonstrates measurement invariance among Chinese and Ghanaian patients. Methods: Measurement invariance tests were conducted using two samples collected from the two cultures respectively (China: N = 598 and Ghana: N = 591). Confirmatory Factor Analysis (CFA) was used to test for the factor structure. Multiple-group CFA was used to test the measurement invariance of the SEGUE between the two samples. Results: The same five-factor model showed acceptable model fit in both Chinese and Ghanaian samples. Cross-cultural measurement invariance tests revealed that scalar invariance was observed across the two samples. Conclusion: Cross-cultural adaptations of instruments should exhibit measurement invariance to ensure that measures are interpreted and used consistently. Findings of our study suggest that the SEGUE Framework is invariant across the two cultures, which increases confidence in data collection and comparison. Innovation: This is the first study to establish measurement invariance among Chinese and Ghanaians using the SEGUE Framework which assesses doctors' communication from patients' perspectives.

The Digital Divide Is Aging: An Intergenerational Investigation of Social Media Engagement in China.

The aging-based digital divide has gained increased research attention in recent years. This research focused on two important aspects of the aging society, the digital divide and the intergenerational differences, with regard to social media usage in China. The data were collected through a household interview, using a nationally representative sample (n= 3790) from 58 cities in mainland China. The present study investigated the association between differentiated social media usage with demographic characteristics, social economic status, physical and mental health, and social media perceptions. The results show a significant digital divide and generational differences. The existing socio-economic inequalities and demographic variance largely explained older adults' social media access and diversity of social media engagement. Social media perceptions play more essential roles in the intensity of social media engagement for each generation group. This study contributes a better understanding of the manner in which different factors are associated with different generations' social media engagement. A discussion is included regarding the necessity to close the aging-based digital gap in order to cope with the issue of rapid aging.

Effects of High-Frequency Chest Wall Oscillation Expectoration System on Pulmonary Rehabilitation and Cortisol Function in Patients with Severe AECOPD.

Objective: To investigate the effect of high-frequency chest wall oscillatory expectoration system (HFCWO) on pulmonary rehabilitation and cortisol function in patients with severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The 65 severe AECOPD patients admitted to our hospital from January 2019 to May 2020 were divided into group A with 33 cases and group B with 32 cases by random number table method. After 14 days of intervention, the improvement time of clinical symptoms in the two groups was recorded, and blood gas, lung function, inflammatory, and cortisol function-related indicators were evaluated before and after treatment. Results: The remission time of expectoration, pulmonary signs, and hospital stay in group A were significantly shorter than those in group B (P < 0.05). Compared with before treatment, blood oxygen partial pressure (PaO2), forced vital capacity (FVC), forced expiratory volume at 1 s (EFV1), and EFV1/FVC increased significantly; blood carbon dioxide partial pressure (PaCO2), C-reactive protein (CRP), interleukin-6 (IL-6), white blood cell count (WBC), plasma cortisol (COR), and adrenocorticotropic hormone (ACTH) levels were significantly decreased, and the above indicators in group A increased or decreased more significantly than those in group B (P < 0.05); there was no significant difference in tolerance and adverse reactions between the two groups (P > 0.05). Conclusion: HFCWO has good pulmonary rehabilitation effect in the treatment of severe AECOPD and can significantly improve the blood gas indexes, inflammation, and cortisol function of patients, which is safe and feasible.

Characterization of Mesenchymal Stem Cells Derived from Bisphosphonate-Related Osteonecrosis of the Jaw Patients' Gingiva.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition that specifically occurs in the oral cavity, characterized by retarded wound healing in oral mucosa accelerating the exposure of bone. Moreover, the pathological mechanism remains poorly understood. Gingival mesenchymal stem cells (GMSCs) play a critical role in gingival healing and soft tissue regeneration. Although previous studies have showed that bisphosphonates (BPs) are highly toxic to healthy GMSC, there is overall lack of direct evidence demonstrating the characterization of GMSCs derived from BRONJ patients. In present study, we isolated GMSCs for the first time from the central area of BRONJ patients' gingiva (center-BRONJ GMSCs) and the peripheral area (peri-BRONJ GMSCs), and found that they exhibited decreased proliferation, adhesion, migration capacities and underwent early apoptosis in vitro compared control GMSCs. Notably, the central and peripheral BRONJ GMSCs transplantation in a mice excisional skin model also displayed lower cell survival rate and poor healing effects than that of controls. Mechanistically, TGF-ß1 signaling pathway was suppressed not only in BRONJ patients' gingival lesions but also in BRONJ GMSCs transplantation animal model. The results above suggested that under the microenvironment of BRONJ patients, the dysfunction of GMSCs and the suppressed TGF-ß1 signaling pathway may be the vital factors in impaired gingival healing, thus contributing to persistent exposure of underlying bone and development of BRONJ. This study provides new insights into the prevention for BRONJ by improving the functions of GMSCs and upregulating TGF-ß1 in accelerating gingival wound healing. Schematic illustration of the dysfunction of BRONJ GMSCs in vitro and BRONJ GMSCs transplantation in a mice skin model delaying cutaneous wound healing mainly via suppressing TGF-ß1 signaling pathway.

A single-cell interactome of human tooth germ from growing third molar elucidates signaling networks regulating dental development.

BACKGROUND: Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) pathways. However, an intact network of the intercellular regulation is still lacking. RESULT: To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the growing third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via Transforming growth factor-ß, Tumor necrosis factor (TNF) and Interleukin-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that Colony Stimulating Factor 1 secreted from pericyte and TNF Superfamily Member 11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. CONCLUSIONS: We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology.

Quantitative Segmentation Analysis of the Radiological Changes by Using ITK-SNAP: Risk Assessment of the Severity and Recurrence of Medication-related Osteonecrosis of the Jaw.

Background and purpose: Medication-related osteonecrosis of the jaw (MRONJ) severely impairs patients' quality of life and is remarkably refractory to treatment. There are lots of studies about identification of the radiographic features of MRONJ, yet reports about quantitative radiographic analysis for the risk assessment of the severity and recurrence of MRONJ are rarely heard. The aim of this study was to investigate the volumes of osteolytic lesions and radiodensity values of osteosclerotic lesions in MRONJ patients by using ITK-SNAP for severity prediction and prognosis evaluation. Materials and methods: Of 78 MRONJ patients (78 lesions) involved in this retrospective study, 53 were presented as osteolytic lesions and 25 were presented as osteosclerotic changes alone. Comprehensive CBCT images, demographics and clinical data of patients were investigated. The volumetric analysis and radiodensity measurement were performed by ITK-SNAP. SPSS 25.0 were used for statistical analysis. Results: The osteolytic lesion volumes in MRONJ patients receiving intravenous bisphosphonates (P=0.004) and patients without osteoporosis (P=0.027) were significantly large. No significant correlation between the volumes and bisphosphonates duration was found (P=0.094). The radiodensity values of osteosclerotic lesions was significantly correlated with bisphosphonates duration (P=0.040). The surrounding area of post-surgical lesions in MRONJ patients with recurrence showed significantly great radiodensity values (P=0.025). No significant correlation between the radiodensity values and the transformation from osteosclerotic lesions to osteolytic lesions was observed (P=0.507). Conclusion: MRONJ patients receiving intravenous bisphosphonates develop into large volumes of osteolytic lesions more easily. Long-term bisphosphonates duration is possibly related with higher bone density of osteosclerotic lesions, while higher density is not associated with the transformation from osteosclerotic lesions to osteolytic lesions. A rise of bone mineral density nearby post-surgical lesions is probably a predictor for MRONJ recurrence.

The effects of CPBL + SBAR teaching mode among the nursing students.

OBJECTIVE: To investigate the effect of CPBL (Problem Based Learning on Case) combined with SBAR (Situation, Background, Assessment and Recommendation) mode in clinical teaching for nursing students. BACKGROUND: Clinical internship training is the key step for the nursing education. The clinical thinking ability of Chinese nurses is mostly at the middle or low level. To improve clinical thinking ability, especially critical thinking, is of great significance to the nursing practice education. METHODS: 102 nursing students of the Third Xiangya Hospital, Central South University were selected as the participants from June 2018 to September 2019. We applied the CPBL + SBAR mode to the participants during the practice teaching, and conducted questionnaires and semi-structured interview pre- and post-intervention. RESULTS: After intervention, the nursing students' scores of critical thinking ability (311.47 ± 22.67) were higher than those before intervention (289.75 ± 19.94); the total score (69.84 ± 6.217) and scores in four dimensions of positive problem orientation (RPO), negative problem orientation (NPO), avoidance style (AS) and impulse neglect style (ICS) were all lower than that before intervention (75.53 ± 6.09); the score of rational problem solving (RPS) (18.38 ± 2.714) was higher comparing to the that of pre-intervention (17.11 ± 2.20); the difference was statistically significant (P < 0.05). The approval rate of nursing students to the positive effect of CPBL + SBAR teaching mode was from 78.43% to 93.13%. The semi-structured interview suggested that the model was worth promoting, but the implementation duration was limited. CONCLUSION: CPBL + SBAR teaching mode could improve the nursing students' critical thinking and problem-solving ability. The nursing students and teachers' satisfaction to the new teaching mode was high.

Activation of mesenchymal stem cells promotes new bone formation within dentigerous cyst.

BACKGROUND: Dentigerous cyst (DC) is a bone destructive disease and remains a challenge for clinicians. Marsupialization enables the bone to regenerate with capsule maintaining, making it a preferred therapeutic means for DC adjacent to vital anatomical structures. Given that capsules of DC are derived from odontogenic epithelium remnants at the embryonic stage, we investigated whether there were mesenchymal stem cells (MSCs) located in DC capsules and the role that they played in the bone regeneration after marsupialization. METHODS: Samples obtained before and after marsupialization were used for histological detection and cell culture. The stemness of cells isolated from fresh tissues was analyzed by morphology, surface marker, and multi-differentiation assays. Comparison of proliferation ability between MSCs isolated from DC capsules before (Bm-DCSCs) and after (Am-DCSCs) marsupialization was evaluated by Cell Counting Kit-8 (CCK-8), fibroblast colony-forming units (CFU-F), and 5'-ethynyl-2'-deoxyuridine (EdU) assay. Their osteogenic capacity in vitro was detected by alkaline phosphatase (ALP) and Alizarin Red staining (ARS), combined with real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF) staining. Subcutaneous ectopic osteogenesis as well as cranial bone defect model in nude mice was performed to detect their bone regeneration and bone defect repairability. RESULTS: Bone tissue and strong ALP activity were detected in the capsule of DC after marsupialization. Two types of MSCs were isolated from fibrous capsules of DC both before (Bm-DCSCs) and after (Am-DCSCs) marsupialization. These fibroblast-like, colony-forming cells expressed MSC markers (CD44+, CD90+, CD31-, CD34-, CD45-), and they could differentiate into osteoblast-, adipocyte-, and chondrocyte-like cells under induction. Notably, Am-DCSCs performed better in cell proliferation and self-renewal. Moreover, Am-DCSCs showed a greater osteogenic capacity both in vitro and in vivo compared with Bm-DCSCs. CONCLUSIONS: There are MSCs residing in capsules of DC, and the cell viability as well as the osteogenic capacity of them is largely enhanced after marsupialization. Our findings suggested that MSCs might play a crucial role in the healing process of DC after marsupialization, thus providing new insight into the treatment for DC by promoting the osteogenic differentiation of MSCs inside capsules.

How we assess the perioperative anxiety of surgical patients with pulmonary nodules: the revision of state-trait anxiety inventory.

PURPOSE: The aim of the study was to develop a short form of State-Trait Anxiety Inventory (STAI) and calculate the norms for the assessment of anxiety in surgical patients in mainland China. METHODS: Patients who were scheduled to carry out pulmonary surgery in our department were included. The sinicized 40-item STAI Form-Y was used to assess the anxiety on the surgery eve. Then the coefficient of variation, coefficient of correlation, stepwise regression analysis, principal component analysis, and structural equation model were successively to filter the items. The reliability and validity of the revised STAI was estimated and the norms were computed. RESULTS: 445 intact replies were collected. A 13-item STAI with 6 items in state subscale and 7 items in trait subscale produced similar scores with the full version of STAI. The Cronbach alpha coefficients for the state and trait subscales were 0.924 and 0.936, respectively. The determinant coefficients were 0.781 and 0.822, respectively. Moreover, the norms of both state subscale and trait subscale are provided according to the age and gender. CONCLUSIONS: The revised short form of STAI has good reliability and validity. It is likely to be more acceptable by reducing the fatigue effects, and is suitable for follow-up study on the assessment and intervention of perioperative anxiety of surgical patients with pulmonary nodules.

Combined Administration of Bisphosphonates, Chemotherapeutic Agents, and/or Targeted Drugs Increases the Risk for Stage 3 Medication-Related Osteonecrosis of the Jaw: A 4-Year Retrospective Study.

OBJECTIVES: Patients with stage 3 medication-related osteonecrosis of the jaw (MRONJ) suffer from severe complications. Chemotherapeutic agents and targeted drugs are considered to be associated with the development of MRONJ. However, little is known regarding the association of those agents with stage 3 MRONJ. The purpose of this study is to analyze the comprehensive medication history of patients with advanced-stage MRONJ (stage 2 and stage 3) and evaluate the possible risk factors for stage 3 MRONJ. Patients and Methods. Sixty patients with advanced-stage MRONJ were involved in this retrospective study. Patients with developmental maxillofacial anomalies, previous radiation in the head and neck areas, and jaw bone tumors were excluded from the study. All patients were divided into two groups by their MRONJ stage (stage 2 or stage 3). Demographic and clinical characteristics, comprehensive medication data (bisphosphonates, chemotherapeutic agents, targeted drugs, and immunosuppressive agents), and results of serological biomarkers were recorded and compared between two groups. Univariate and multivariate logistic regressions were performed by SPSS 25.0 for evaluating risk factors of stage 3 MRONJ. RESULTS: Our results indicate that chemotherapy (adjusted OR = 3.43; 95% CI: 1.03 to 11.38), targeted drugs (adjusted OR = 3.69; 95% CI: 1.06 to 12.80), and maxillary lesions (adjusted OR = 4.26; 95% CI: 1.19 to 15.23) increase the risk of stage 3 MRONJ. CONCLUSION: The outcome of this study justifies that chemotherapeutic agents and targeted drugs are probably risk factors for stage 3 MRONJ. In addition, the osteonecrosis in maxilla is more easily to develop into stage 3 MRONJ. Intense clinical observation is recommended in MRONJ patients with maxillary osteonecrosis and in those who concurrently administered bisphosphonates, chemotherapeutic agents, and/or targeted drugs. This trial is registered with ChiCTR2000032428.

Stress response in periodontal ligament stem cells may contribute to bisphosphonate­associated osteonecrosis of the jaw: A gene expression array analysis.

Gene expression alterations in periodontal ligament stem cells (PDLSCs) during bisphosphonate (BP) usage and the transcriptomic mechanism underlying BP­related osteonecrosis of the jaw have not been fully elucidated. In the present study, human PDLSCs were isolated from adults with no history of periodontal disease, and subsequently incubated and treated with zoledronate on days 3 and 5. Subsequently, PDLSCs from all timepoints were screened using an Affymetrix Gene Expression Array. Limma differential expression analysis was performed on a normalized gene expression matrix, followed by cluster analysis, pathway and network analyses. Overall, 906 genes (352 upregulated and 554 downregulated) exhibited differential expression levels between days 0 and 5, and these were termed slow­response genes. These slow­response genes were enriched in cellular stress response signaling pathways (upregulated genes), as well as proliferation­ and ossification­associated signaling pathways (downregulated genes). Furthermore, 168 (day 3 vs. 0) and 105 (day 5 vs. 3) genes were differentially expressed between adjacent timepoints. These genes were also enriched in stress response­ and proliferation­associated signaling pathways, but not in ossification­associated signaling pathways. Poly(ADP­ribose) polymerase 1 (PARP1) and CYLD lysine 63 deubiquitinase (CYLD) had the most protein­protein interaction partners among the slow­response genes and were connected with both stress­ (e.g. caspase­1) and ossification­associated genes [e.g. secreted phosphoprotein 1 and collagen type I α1 chain (COL1A1)]. BP treatment induced stress response­like transcriptional alterations in PDLSCs, followed by inhibition of proliferation and ossification. These alterations may contribute to the onset of jaw osteonecrosis. PARP1 and CYLD may be two key genes involved in this pathological procedure.

Clinical Comparison of Airway Stent Placement in Intervention Room and Operating Room.

BACKGROUND: Airway stent placement is the effective regimen for central airway obstruction (CAO), while its application scenarios varied. This study aimed to make clinical comparison of airway stent placement in the intervention room and operating room. METHODS: Patients underwent airway stent placement between 2014 and 2018 were included in this retrospective case-control study. Clinical performance of airway stent placement in intervention room and operating room were compared. RESULTS: 82 patients were included in this study, including 39 in the intervention room and 43 in the operating room. Patients treated in the intervention room had lower Charlson comorbidity index (CCI) (P=0.018) and received less Y-shaped stents (P<0.001). Better clinical response (P=0.026), more stents placed (P<0.001) and longer length of stent (P<0.001) were observed in operating room, while there was no significantly statistical difference of stent-related complications and post-stent survival rate between the two groups. Extracorporeal membrane oxygenation (ECMO) supported airway stent placement procedures were performed in the operating room, which provided definitive safety support for high-risk intervention. CONCLUSIONS: Patients with CAO could benefit from the operating room scenario, and airway stent placement in the operating room is more suitable for patients with higher CCI scores and receiving more complicated procedures.

Decreased Osteogenic Ability of Periodontal Ligament Stem Cells Leading to Impaired Periodontal Tissue Repair in BRONJ Patients.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe adverse reaction, which results in progressive bone destruction in the maxillofacial region of patients. To date, the pathological mechanisms remain largely unclear. Recently, we found that BRONJ patient had significantly deep periodontal pockets and severe periodontal bone defects before the exposed necrotic bone. Human periodontal ligament stem cells (hPDLSCs) play key roles in physiological maintenance and regeneration of periodontal tissues. However, the activities of hPDLSCs derived from BRONJ lesions and the role of hPDLSCs in BRONJ periodontal defect repair remain poorly understood. The aim of the present study was to elucidate the role of hPDLSCs in BRONJ. In this study, we found that the capacities of cell proliferation, adhesion, and migration of hPDLSCs derived from BRONJ lesions (BRONJ-hPDLSCs) were significantly decreased compared with control-hPDLSCs. BRONJ-hPDLSCs underwent early apoptosis compared with control-hPDLSCs. Importantly, we first demonstrated that BRONJ-hPDLSCs exhibited impaired osteogenic differentiation abilities in ectopic osteogenesis of nude mice. The above results suggested that the impaired BRONJ-hPDLSCs may be an important factor in deficient periodontal repair of BRONJ lesions and provide new insight into the underlying mechanism of BRONJ.

A switchable electrochromism and electrochemiluminescence bifunctional sensor based on the electro-triggered isomerization of spiropyran/layered double hydroxides.

A bifunctional ultrathin film (UTF) electrode was fabricated based on layered double hydroxides (LDHs) and spiropyran (SP), which exhibited electrochromism and electrochemiluminescence (ECL) sensing behavior toward temperature and Zn2+ ions.

Autocrine TNF-α-mediated NF-κB activation is a determinant for evasion of CD40-induced cytotoxicity in cancer cells.

Activation of CD40 by CD40L results in diverse effects on different malignant cells, causing either promotion of survival, growth and resistance to chemotherapy, or induction of cytostasis and apoptosis. The molecular mechanisms underlying CD40-mediated growth regulation and apoptosis induction in cancer cell are not fully understood. In this study, we investigated the role of NF-κB activation in CD40-mediated cytotoxicity in cancer cells. The results show that activation of CD40 by recombinant soluble CD40 ligand (rsCD40L) readily induced NF-κB activation and blocking NF-κB significantly enhanced rsCD40L-induced apoptosis in cancer cells. Importantly, autocrine of TNF-α induced by rsCD40L was indispensable for both NF-κB activation and cytotoxicity induction, establishing a dual role of autocrine TNF-α that constitutes both pro-apoptotic and anti-apoptotic arms of CD40 signaling. Our results indicate that autocrine TNF-α-mediated NF-κB activation is a determinant for cancer cells' evasion of CD40L-induced cytotoxicity and blocking NF-κB may have potential for improve the value of CD40 as an anticancer agent.

Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins.

Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with other agents is a promising strategy to overcome TRAIL resistance in malignant cells. Wogonin, a flavonoid originated from Scutellaria baicalensis Georgi, has been shown to enhance TRAIL-induced apoptosis in malignant cells in in vitro studies. However, whether wogonin enhances TRAIL's antitumor activity in vivo has never been studied. In this study, the effect of combination of TRAIL and wogonin was tested in a non-small-cell lung cancer xenografted tumor model in nude mice. Consistent with the in vitro study showing that wogonin sensitized A549 cells to TRAIL-induced apoptosis, wogonin greatly enhanced TRAIL-induced suppression of tumor growth, accompanied with increased apoptosis in tumor tissues as determined by TUNEL assay. The expression levels of antiapoptotic proteins including long form of cellular FLICE-like inhibitory protein (cFLIPL), X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) were markedly reduced in both cultured cells and xenografted tumor tissues after co-treatment with wogonin and TRAIL. The down-regulation of these antiapoptotic proteins was likely mediated by proteasomal degradation that involved intracellular reactive oxygen species (ROS), because wogonin robustly induced ROS accumulation and ROS scavengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) and the proteasome inhibitor MG132 restored the expression of these antiapoptotic proteins in cells co-treated with wogonin and TRAIL. These results show for the first time that wogonin enhances TRAIL's antitumor activity in vivo, suggesting this strategy has an application potential for clinical anticancer therapy.

[Recombinant soluble CD40 ligand enhances Wogonin-induced antitumor activity].

OBJECTIVE: To investigate the effect of recombinant soluble CD40 ligand (rsCD40L) on Wogonin mediated antitumor activity in cancer cells and the underlying molecular mechanisms. METHODS: Cell death was detected based on the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. For morphological study of cell death, cells were stained with 50 microg/mL of acridine orange and 50 microg/mL of ethidium bromide and observed and photographed under a fluorescence microscope. Activation of apoptosis pathway was evaluated by Western blot. The effects of pan-caspase inhibitor Z-VAD-FMK and tumor necrosis factor alpha (TNF-alpha) neutralizing antibody on cell death induced by rsCD40L and Wogonin co-treatment were also investigated. RESULTS: rsCD40L significantly enhanced Wogonin-induced cell death of ovarian cancer cells SKOV3. A dose-dependent synergism was found with a fixed rsCD40L dose (1 microg/mL) and increased concentrations of Wogonin (5 micromol/L-15 micromol/L). rsCD40L and Wogonin co-treated cells showed typical apoptotic morphologies and enhanced activation of caspases pathway. As expected, the pan-caspase inhibitor Z-VAD-FMK inhibited synergistic cell death of rsCD40L and Wogonin co-treated SKOV3 cells. Interestingly, the TNF-alpha neutralizing antibody that blocks TNF-alpha binding to its receptor also significantly suppressed the cell death enhancing effect, indicating that autocrine TNF-alpha played a role of sensitization. CONCLUSION: rscCD40L sensitizes cancer cells to wogonin-mediated apoptosis, which may involve autocrine of TNF-alpha, and the combination of rsCD40L and Wogonin may have a potential for cancer therapy.