Octacalcium phosphate, a promising bone substitute material: a narrative review.

Biomaterials have been used to supplement and restore function and structure by replacing or restoring parts of damaged tissues and organs. In ancient times, the medical use of biomaterials was limited owing to infection during surgery and poor surgical techniques. However, in modern times, the medical applications of biomaterials are diversifying owing to great developments in material science and medical technology. In this paper, we introduce biomaterials, focusing on calcium phosphate ceramics, including octacalcium phosphate, which has recently attracted attention as a bone graft material.

Study Protocol for a Hospital-to-Home Transitional Care for Older Adults Hospitalized with Chronic Obstructive Pulmonary Disease in South Korea: A Randomized Controlled Trial.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by persistent inflammation in the airways, resulting in narrowing and obstruction of the air passages. The development of COPD is primarily attributed to long-term exposure to irritants, such as cigarette smoke and environmental pollutants. Among individuals hospitalized for exacerbations of COPD, approximately one in five is readmitted within 30 days of discharge or encounters immediate post-discharge complications, highlighting a lack of adequate preparedness for self-management. To address this inadequate preparedness, transitional care services (TCS) have emerged as a promising approach. Therefore, this study primarily aims to present a detailed protocol for a multi-site, single-blind, randomized, controlled trial (RCT) aimed at enhancing self-management competency and overall quality of life for patients with COPD through the provision of TCS, facilitated by a proficient Clinical Research Coordinator. The RCT intervention commenced in September 2022 and is set to conclude in December 2024, with a total of 362 COPD patients anticipated to be enrolled in the study. The intervention program encompasses various components, including an initial assessment during hospitalization, comprehensive self-management education, facilitation of social welfare connections, post-discharge home visits, and regular telephone monitoring. Furthermore, follow-up evaluations are conducted at both one month and three months after discharge to assess the effectiveness of the intervention in terms of preventing re-hospitalization, reducing acute exacerbations, and enhancing disease awareness among participants. The results of this study are expected to provide a basis for the development of TCS fee payment policies for future health insurance.

Effects of Transitional Care after Hospital Discharge in Patients with Chronic Obstructive Pulmonary Disease: An Updated Systematic Review and Meta-Analysis.

This study aimed to systematically review the effects of transitional care programs on healthcare use and quality of life in patients with chronic obstructive pulmonary disease (COPD). Several databases were searched for randomized controlled trials conducted over the past five years, and their quality was evaluated using the Cochrane Risk of Bias 2.0 tool. For indicators with available statistical information, a meta-analysis was performed using RevMan 5.4, and a narrative review was performed for the rest of the results. In the meta-analysis, no statistically significant difference was observed between the intervention and control groups in the number of readmissions and emergency room visits due to COPD. The relative risk (RR) of readmission for COPD was lower in the intervention group. Respiratory-related quality of life tended to be better in the intervention group, though not significantly. Physical capacity was improved in the intervention group. Considering the characteristics of the complex intervention, the context and factors of cases where the expected results could be obtained and cases where the expected results could not be obtained were reviewed and discussed. Based on the results of the analysis, implications for the development of better protocols were presented.

Development of Cellular Signaling Pathways by Bioceramic Heat Treatment (Sintering) in Osteoblast Cells.

Bioceramics are calcium-phosphate-based materials used in medical and dental implants for replacing or repairing damaged bone tissues; however, the effect of bioceramic sintering on the intracellular signaling pathways remains unknown. In order to address this, we analyzed the impact of sintering on the cell signaling pathways of osteoblast cells using sintered and non-sintered hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP). X-ray diffraction indicated that only the morphology of HA was affected by sintering; however, the sintered bioceramics were found to have elevated the calcium concentrations in relation to the non-sintered variants. Both bioceramics inhibited the JNK signaling pathway; the sintered HA exhibited half the value of the non-sintered variant, while the sintered ß-TCP rarely expressed a p-JNK value. The total Src and Raptor protein concentrations were unaffected by the sintering, while the p-Src concentrations were decreased. The p-EGFR signaling pathway was regulated by the non-sintered bioceramics, while the p-p38 concentrations were reduced by both the sintered ß-TCP and HA. All of the bioceramics attenuated the total AKT concentrations, particularly the non-sintered HA, and the AKT phosphorylation concentration, except for the non-sintered ß-TCP. Thus, the sintering of bioceramics affects several intracellular signaling pathways. These findings may elucidate the bioceramic function and expand their application scope as novel substrates in clinical applications.

Chiral Supramolecular Multiblock Copolymerization Accompanying Chirality Transfer in Heterostructures via Living Chain Growth.

We report the unique synthesis of chiral supramolecular tri- and penta-BCPs with controllable chirality using kinetically adjusted seeded supramolecular copolymerization in THF and DMSO (99 : 1, v/v). Tetraphenylethylene (d- and l-TPE) derivatives bearing d- and l-alanine side chains formed thermodynamically favored chiral products via a kinetically trapped in monomeric state with a long lag phase. In contrast, achiral TPE-G containing glycine moieties did not form a supramolecular polymer owing to the energy barrier in its kinetically trapped state. We show that the copolymerization of the metastable states of TPE-G not only enables the generation of supramolecular BCPs by the seeded living growth method, but also transfers chirality at the seed ends. This research demonstrates the generation of chiral supramolecular tri- and penta-BCPs with B-A-B, A-B-A-B-A, and C-B-A-B-C block patterns accompanying chirality transfer via seeded living polymerization.

Effects of Client-Centered Occupational Therapy on Behavioral Psychological Symptoms, Social Interaction, Occupational Performance, Quality of Life, and Caregiver Burden among the Individuals with Dementia.

This study aimed to verify the effects of client-centered occupational therapy on individuals with dementia. Twenty participants were randomly assigned to an experimental group (client-centered occupational therapy) and a control group (general occupational therapy). A pretest, post-test, and follow-up tests were used to compare the effects of the intervention. The experimental group had significant changes in all variables, and the control group showed significant differences in verbal social interaction, quality of life, and burden of caregivers (p < 0.05). As a result of repeated measurement variance analysis, it was found that there was a significant effect within the group except for the NPI-Q distress items (p < 0.05), but the effect was not verified in all areas between the groups. Client-centered customized occupational therapy can be more effective than general occupational therapy in problem behavior, social interaction, quality of life, caregiver burden, and occupational performance of individuals with dementia.

An exploratory study on the role of occupational therapists in home-based rehabilitation team in South Korea.

Introduction: Cooperation among rehabilitation team members is essential in the home-based rehabilitation setting. Q-methodology that can quantitatively analyze the subjectivity of members of the rehabilitation team was used to explore the role of occupational therapists (OTs) in home-based rehabilitation. Methods: The Q-methodology process was implemented in five steps: Step 1 - Representative statements about the role of OTs were collected through in-depth interviews, open questionnaires, and literature reviews (Q-sample); Step 2 - A total of 34 rehabilitation team members (physical therapists, OTs, social workers, nutritionists) were recruited (P-sample); Step 3 - The statements were classified according to their subjective perspective (Q-sort); Step 4 - Factor analysis was performed based on the correlation among the responses from the participants (Q-factor analysis); Step 5 - The awareness factor for roles was interpreted (Interpretation of awareness factors). Results: The roles of OTs perceived by members of the home-based rehabilitation team were formed into five factors (A) Adaptation within home environments; (B) Professional development; (C) Reliable service execution; (D) Client needs resolution; and (E) Focus on activity participation. In all factors, perspectives on the role of OTs in helping clients participate in their roles and activities at home were included. These factors included issues and directions addressed in prior literature on the development of occupational therapy. Conclusions: In home-based rehabilitation, OTs must play a professional role in ensuring clients live fully at home, and cooperate with team members for an effective rehabilitation approach.

Exploring bacterioplankton communities and their temporal dynamics in the rearing water of a biofloc-based shrimp (Litopenaeus vannamei) aquaculture system.

Biofloc technology (BFT) has recently gained considerable attention as a sustainable method in shrimp aquaculture. In a successful BFT system, microbial communities are considered a crucial component in their ability to both improve water quality and control microbial pathogens. Yet, bacterioplankton diversity in rearing water and how bacterioplankton community composition changes with shrimp growth are rarely documented. In this study, the Pacific white shrimp, Litopenaeus vannamei was cultivated in a greenhouse-enclosed BFT system. Rearing water samples were collected on a weekly basis for 5 months (152 days) and water quality variables such as physicochemical parameters and inorganic nutrients were monitored. In parallel, 16S rRNA gene pyrosequencing was employed to investigate the temporal patterns of rearing-water microbiota. The productivity, survival rate, and feed conversion ratio were 3.2-4.4 kg/m3, 74%-89%, and 1.2-1.3, respectively, representing successful super-intensive cultures. The metataxonomic results indicated a highly dynamic bacterioplankton community, with two major shifts over the culture. Members of the phylum Planctomycetes dominated in rearing water during the early stages, while Actinobacteria dominated during the middle stages, and Chloroflexi and TM7 dominated during the late stages of culture. The bacterioplankton community fluctuated more in the beginning but stabilized as the culture progressed. Intriguingly, we observed that certain bacterioplankton groups dominated in a culture-stage-specific manner; these groups include Rhodobacteraceae, Flavobacteriaceae, Actinobacteria, and Chloroflexi, which either contribute to water quality regulation or possess probiotic potential. Altogether, our results indicate that an operationally successful BFT-based aquaculture system favors the growth and dynamics of specific microbial communities in rearing water. Our study expands the scientific understanding of the practical utilization of microbes in sustainable aquaculture. A thorough understanding of rearing-water microbiota and factors influencing their dynamics will help to establish effective management strategies.

Multiple proliferation signaling pathways are modulated by octacalcium phosphate in osteoblasts.

Octacalcium phosphate (OCP), a type of bioactive ceramics, may be associated with dentine, tooth apatite, and especially bone generation, and promotes wound healing after fracture. Recently, commercial bone grafting products containing a large amount of OCP material have been released because OCP can be synthesized in large quantities. It is reported to increase cell proliferation, but the interaction between OCP and cell signaling pathways is still unclear. In this study, first, we demonstrated OCP mediated cell signaling pathways with only purified OCP materials. OCP regulated P38, JNK (c-Jun N-terminal kinase), Src, and AKT (protein kinase B) signaling pathways. OCP crystals appeared in the characteristic ribbon shape but varied by several tens of micrometers in size. The X-ray diffraction pattern was the same as previously reported. We studied two concentrations of OCP (10 mg/ml and 20 mg/ml) to understand whether the effect of OCP on cell signaling pathways is dose dependent. We confirmed that OCP treatment affected cell proliferation and alkaline phosphatase and disrupted Src phosphorylation but did not change the total protein level. P38 phosphorylation was activated with OCP treatment and inhibited by SB203580, but P38 total protein level did not change. OCP inhibited JNK phosphorylation signaling, whereas PD98509 inhibited JNK phosphorylation with or without OCP. Interestingly, the AKT total level decreased after OCP treatment, but AKT phosphorylation increased considerably. Our results demonstrate that OCP materials modulate cell signaling pathways and increase cell proliferation.

Radiographic and Histomorphometric Evaluation of Sinus Floor Augmentation Using Biomimetic Octacalcium Phosphate Alloplasts: A Prospective Pilot Study.

This prospective single-arm clinical study aimed to radiographically and histomorphometrically evaluate the efficacy of the lateral approach for sinus floor elevation (LSFE) using biomimetic octacalcium phosphate (OCP) synthetic bone graft (Bontree®). LSFE using Bontree® was performed on 10 patients (15 implant placement sites) willing to undergo implant surgery, followed by implant placements after 6 months of the healing period. The vertical bone height (VBH) and Hounsfield unit (HU) values at each implant placement site were evaluated radiographically using cone-beam computed tomography at baseline immediately after surgery (T1) and 6 months after surgery (T2). A histomorphometric evaluation of the bone core biopsy specimen was also performed. The mean VBH and HU changes at all sites included a decrease by 0.91 mm and a statistically significant increase by 431.86, respectively, from T1 to T2. The mean ratio of the newly formed bone (23.34% ± 10.63%) was greater than that of the residual bone graft (19.09% ± 8.74%), indicating that Bontree® is effective for new bone formation. This pilot study suggests that Bontree® is a promising bone substitute for LSFE.

Bimetallic Nanocatalysts Immobilized in Nanoporous Hydrogels for Long-Term Robust Continuous Glucose Monitoring of Smart Contact Lens.

Smart contact lenses for continuous glucose monitoring (CGM) have great potential for huge clinical impact. To date, their development has been limited by challenges in accurate detection of glucose without hysteresis for tear glucose monitoring to track the blood glucose levels. Here, long-term robust CGM in diabetic rabbits is demonstrated by using bimetallic nanocatalysts immobilized in nanoporous hydrogels in smart contact lenses. After redox reaction of glucose oxidase, the nanocatalysts facilitate rapid decomposition of hydrogen peroxide and nanoparticle-mediated charge transfer with drastically improved diffusion via rapid swelling of nanoporous hydrogels. The ocular glucose sensors result in high sensitivity, fast response time, low detection limit, low hysteresis, and rapid sensor warming-up time. In diabetic rabbits, smart contact lens can detect tear glucose levels consistent with blood glucose levels measured by a glucometer and a CGM device, reflecting rapid concentration changes without hysteresis. The CGM in a human demonstrates the feasibility of smart contact lenses for further clinical applications.

Smart Wireless Near-Infrared Light Emitting Contact Lens for the Treatment of Diabetic Retinopathy.

Diabetic retinopathy is currently treated by highly invasive repeated therapeutic injections and surgical interventions without complete vision recovery. Here, a noninvasive smart wireless far red/near-infrared (NIR) light emitting contact lens developed successfully for the repeated treatment of diabetic retinopathy with significantly improved compliance. A far red/NIR light emitting diode (LED) is connected with an application-specific integrated circuit chip, wireless power, and communication systems on a PET film, which is embedded in a silicone elastomer contact lens by thermal crosslinking. After in vitro characterization, it is confirmed that the retinal vascular hyper-permeability induced by diabetic retinopathy in rabbits is reduced to a statistically significant level by simply repeated wearing of smart far red/NIR LED contact lens for 8 weeks with 120 µW light irradiation for 15 min thrice a week. Histological analysis exhibits the safety and feasibility of LED contact lenses for treating diabetic retinopathy. This platform technology for smart LED contact lens would be harnessed for various biomedical photonic applications.

Effects of assistive technology-based occupational therapy on community-dwelling people recovering from stroke.

PURPOSE: The purpose of this study was to investigate the effect of assistive technology-based occupational therapy on occupational performance, satisfaction, and psychosocial impacts of community-dwelling people recovering from stroke. METHODS: A total of eleven community-dwelling people recovering from stroke participated in an occupational therapy intervention based on the core concepts of the Human Activity Assistive Technology (HAAT) model. The intervention involved the adoption of assistive technology devices (ATDs) to perform individual goal activities in the daily lives of people recovering from stroke. The intervention was conducted weekly as a 30-min session for a total of 4 weeks, in the home where each participant actually resided. RESULTS: All participants in the intervention showed statistically significant improvements in occupational performance, satisfaction, and goal attainment level with regard to the individually meaningful activities, between pretest, posttest, and follow-up. User satisfaction with the ATDs and associated services was generally 'satisfactory,' and the mean score significantly increased from post-intervention to follow-up. The psychosocial impact of assistive technologies significantly improved from post-intervention to follow-up evaluation. CONCLUSION: Interventions involving concepts, processes, and strategies based on the HAAT model should be continuously performed to select and adopt appropriate interventions involving assistive technologies.

Biomimetic Octacalcium Phosphate Bone Has Superior Bone Regeneration Ability Compared to Xenogeneic or Synthetic Bone.

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations on OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 µm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p < 0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralization), as well as providing additional space for new bone formation by rapid resorption.

A Deep Learning Algorithm to Predict Hazardous Drinkers and the Severity of Alcohol-Related Problems Using K-NHANES.

Purpose: The number of patients with alcohol-related problems is steadily increasing. A large-scale survey of alcohol-related problems has been conducted. However, studies that predict hazardous drinkers and identify which factors contribute to the prediction are limited. Thus, the purpose of this study was to predict hazardous drinkers and the severity of alcohol-related problems of patients using a deep learning algorithm based on a large-scale survey data. Materials and Methods: Datasets of National Health and Nutrition Examination Survey of South Korea (K-NHANES), a nationally representative survey for the entire South Korean population, were used to train deep learning and conventional machine learning algorithms. Datasets from 69,187 and 45,672 participants were used to predict hazardous drinkers and the severity of alcohol-related problems, respectively. Based on the degree of contribution of each variable to deep learning, it was possible to determine which variable contributed significantly to the prediction of hazardous drinkers. Results: Deep learning showed the higher performance than conventional machine learning algorithms. It predicted hazardous drinkers with an AUC (Area under the receiver operating characteristic curve) of 0.870 (Logistic regression: 0.858, Linear SVM: 0.849, Random forest classifier: 0.810, K-nearest neighbors: 0.740). Among 325 variables for predicting hazardous drinkers, energy intake was a factor showing the greatest contribution to the prediction, followed by carbohydrate intake. Participants were classified into Zone I, Zone II, Zone III, and Zone IV based on the degree of alcohol-related problems, showing AUCs of 0.881, 0.774, 0.853, and 0.879, respectively. Conclusion: Hazardous drinking groups could be effectively predicted and individuals could be classified according to the degree of alcohol-related problems using a deep learning algorithm. This algorithm could be used to screen people who need treatment for alcohol-related problems among the general population or hospital visitors.

sFlt-1/PlGF ratio as a predictive and prognostic marker for preeclampsia.

OBJECTIVE: Preeclampsia is clinically unpredictable and associated with adverse outcomes. Pregnant women with suspected preeclampsia require intensive monitoring or hospitalization for elevated sFlt-1 (soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) ratios before symptoms arise. We aimed to determine the sFlt-1/PlGF ratio's usefulness in predicting adverse pregnancy outcomes in preeclampsia. METHODS: From January 2017 to February 2019, we measured the sFlt-1/PlGF ratio in 73 singleton pregnant women suspected of preeclampsia and classified them into three groups: low-risk (sFlt-1/PlGF ratio < 38, n = 19), intermediate (38 ≤ ratio < 85, n = 9), and high-risk (ratio ≥ 85, n = 32). RESULTS: Although the low- and high-risk groups both experienced weight gain during pregnancy, their body mass index (BMI) differed after pregnancy (p = 0.004). The number of women who had been taking antihypertensive medications for chronic hypertension since early pregnancy was higher in the low-risk group (31.6% vs. 22.2%, 6.7%). The gestational weeks at birth were lower in the high-risk group compared to that of the low-risk group (32.0 weeks vs. 35.79 weeks, p < 0.001). In the high-risk group, the average neonatal weight was significantly lighter (p = 0.021), and the period of stay in the neonatal intensive care unit was longer than that in the low-risk group (p = 0.003). CONCLUSION: The sFlt-1/PlGF ratio is a useful indicator of preeclampsia severity and can be utilized as a prognostic marker.

Effects on the survival rates, hematological parameters, and neurotransmitters in olive flounders, Paralichthys olivaceus, reared in bio-floc and seawater by Streptococcus iniae challenge.

Bacterial infections cause huge losses to aquaculture globally, and increased antibiotic resistance means that alternative methods of reducing mortality from bacterial diseases are required. We compared the resistance of Juvenile olive flounders, Paralichthys olivaceus, to Streptococcus iniae between those reared in biofloc and seawater conditions for ten months. Experimental fish were challenged with S. iniae at concentrations of 0, 3.36 × 106, 3.36 × 107, 3.36 × 108, and 3.36 × 109 colony forming units (CFU)/g fish for 96 h to evaluate the difference in S. iniae susceptibility of flounders reared in biofloc and seawater. The 96 h lethal concentration 50% (LC50) of fish injected with S. iniae was 2.41 × 109 CFU/g fish in biofloc and 1.51 × 108 CFU/g fish in seawater. Hematological parameters such as hemoglobin and hematocrit significantly decreased when fish were challenged by S. iniae. Plasma components such as calcium, glucose, cholesterol, total protein, GOT, GPT, and ALP were significantly altered by S. iniae infection and acetylcholinesterase activity was significantly inhibited. These results indicate that S. iniae infection affects the survival rates, hematological parameters, and neurotransmitter levels of flounders reared in biofloc and seawater, and that S. iniae susceptibility was higher in flounders reared in seawater than those reared in biofloc.

Proposal and Assessment of a De-Identification Strategy to Enhance Anonymity of the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) in a Public Cloud-Computing Environment: Anonymization of Medical Data Using Privacy Models.

BACKGROUND: De-identifying personal information is critical when using personal health data for secondary research. The Observational Medical Outcomes Partnership Common Data Model (CDM), defined by the nonprofit organization Observational Health Data Sciences and Informatics, has been gaining attention for its use in the analysis of patient-level clinical data obtained from various medical institutions. When analyzing such data in a public environment such as a cloud-computing system, an appropriate de-identification strategy is required to protect patient privacy. OBJECTIVE: This study proposes and evaluates a de-identification strategy that is comprised of several rules along with privacy models such as k-anonymity, l-diversity, and t-closeness. The proposed strategy was evaluated using the actual CDM database. METHODS: The CDM database used in this study was constructed by the Anam Hospital of Korea University. Analysis and evaluation were performed using the ARX anonymizing framework in combination with the k-anonymity, l-diversity, and t-closeness privacy models. RESULTS: The CDM database, which was constructed according to the rules established by Observational Health Data Sciences and Informatics, exhibited a low risk of re-identification: The highest re-identifiable record rate (11.3%) in the dataset was exhibited by the DRUG_EXPOSURE table, with a re-identification success rate of 0.03%. However, because all tables include at least one "highest risk" value of 100%, suitable anonymizing techniques are required; moreover, the CDM database preserves the "source values" (raw data), a combination of which could increase the risk of re-identification. Therefore, this study proposes an enhanced strategy to de-identify the source values to significantly reduce not only the highest risk in the k-anonymity, l-diversity, and t-closeness privacy models but also the overall possibility of re-identification. CONCLUSIONS: Our proposed de-identification strategy effectively enhanced the privacy of the CDM database, thereby encouraging clinical research involving multiple centers.

Wireless smart contact lens for diabetic diagnosis and therapy.

A smart contact lens can be used as an excellent interface between the human body and an electronic device for wearable healthcare applications. Despite wide investigations of smart contact lenses for diagnostic applications, there has been no report on electrically controlled drug delivery in combination with real-time biometric analysis. Here, we developed smart contact lenses for both continuous glucose monitoring and treatment of diabetic retinopathy. The smart contact lens device, built on a biocompatible polymer, contains ultrathin, flexible electrical circuits and a microcontroller chip for real-time electrochemical biosensing, on-demand controlled drug delivery, wireless power management, and data communication. In diabetic rabbit models, we could measure tear glucose levels to be validated by the conventional invasive blood glucose tests and trigger drugs to be released from reservoirs for treating diabetic retinopathy. Together, we successfully demonstrated the feasibility of smart contact lenses for noninvasive and continuous diabetic diagnosis and diabetic retinopathy therapy.

Synergistic anticancer effect of combined use of Trichosanthes kirilowii with cisplatin and pemetrexed enhances apoptosis of H1299 non-small-cell lung cancer cells via modulation of ErbB3.

BACKGROUND: Lung cancer is one of the most common malignancies worldwide. To treat lung cancer, various anticancer drugs were developed and tested, but they failed because of drug resistance. In the present study, we tested herbal medicines, such as TK and CuD, as anticancer drugs to decrease side effects and resistance. METHODS: Cell viability was measured by an MTT assay. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by an annexin V-FITC/PI assay. We performed RTK kit analysis. Levels of p-ErbB3, p-STAT3, p-NF-κB, and caspases were measured by western blot analysis. Nuclear staining of ErbB3 was measured by immunocytochemistry. Transcriptional activity of STAT3 and NF-κB was detected by STAT3 and NF-κB luciferase reporter gene assays. RESULTS: We found a synergistic effect of TK with CDDP and PXD in primary culture of human NSCLC tumor cells. The combination of CDDP/PXD and TK or CuD inhibited the proliferation of H1299 cells. The combination of CDDP/PXD and TK or CuD induced sub-G1 and G2/M cell cycle arrest in H1299 cells. The combination of CDDP/PXD and TK or CuD induced apoptosis, regulated apoptotic molecules, caused morphological changes and inhibited colony formation in H1299 cells. We found that TK suppresses p-ErbB3 expression and signaling. The combination of CDDP/PXD and TK or CuD inhibited p-AKT, p-Erk, and p-JNK signaling and suppressed Stat3 and NF-κB transcriptional activity in H1299 cells. More importantly, the combination of CDDP/PXD and TK or CuD inhibited p-ErbB3 and downstream molecules in H1299 cells. The combination of CDDP/PXD and TK or CuD inhibited ErbB2/ErbB3 dimerization. Our results clearly demonstrate that the synergistic effect of CDDP/PXD and TK or CuD inhibits cell growth and induces apoptosis by inhibiting ErbB3 signaling. CONCLUSION: The combination of CDDP/PXD and TK or CuD decreases cell proliferation and induces apoptosis by inhibiting ErbB3 signaling in H1299 lung cancer cells. TK or CuD could be useful as a compound to treat lung cancer. Additionally, targeting ErbB3 may also be useful for treating lung cancer.