Attenuative effects of collagen peptide from milkfish (Chanos chanos) scales on ovariectomy-induced osteoporosis.

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

The impact of surgical learning curve on short-term outcomes after bilateral lung transplantation: results from a multidisciplinary surgical team.

OBJECTIVES: The aim of this study was to examine the impact of surgical learning curve on short-term clinical outcomes of patients after bilateral lung transplantation (LTx) performed by a surgical multidisciplinary team (MDT). METHODS: Forty-two patients underwent double LTx from December 2016 to October 2021. All procedures were performed by a surgical MDT in a newly established LTx program. The time required for bronchial, left atrial cuff and pulmonary artery anastomoses was the main end point to assess surgical proficiency. The associations between the surgeon's experience and procedural duration were examined by linear regression analysis. We employed the simple moving average technique to generate learning curves and evaluated short-term outcomes before and after achieving surgical proficiency. RESULTS: Both total operating time and total anastomosis time were inversely associated with the surgeon's experience. On analysing the learning curve for bronchial, left atrial cuff and pulmonary artery anastomoses using moving averages, the inflection points occurred at 20, 15 and 10 cases, respectively. To assess the learning curve effect, the study cohort was divided into early (cases 1-20) and late (cases 21-42) groups. Short-term outcomes-including intensive care unit stay, in-hospital stay and severe complications-were significantly more favourable in the late group. Furthermore, there was a notable tendency for patients in the late group to experience a decreased duration of mechanical ventilation along with reduced instances of grade 3 primary graft dysfunction. CONCLUSIONS: A surgical MDT can perform double LTx safely after 20 procedures.

Renoprotective Impacts of Inonotus obliquus Ethanol-Ethyl Acetate Extract on Combined Streptozotocin and Unilateral Nephrectomy-Induced Diabetic Nephropathy in Mice.

Diabetes nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) globally. Medication options to stop or slow the progression of chronic renal disease (CKD) are limited, and patients with DN remain at a high risk of developing renal failure. Inonotus obliquus extracts (IOEs) of Chaga mushroom have been shown to have anti-glycemic, anti-hyperlipidemia, antioxidant, and anti-inflammatory effects against diabetes. In this study, we examined the potential renal protective role of an ethyl acetate layer after water-ethyl acetate separation from Inonotus obliquus ethanol crude extract (EtCE-EA) from Chaga mushrooms in diabetic nephropathy mice after preparation with 1/3 NT + STZ. Our data showed that treatment with EtCE-EA can effectively regulate blood glucose, albumin-creatinine ratio, serum creatinine, and blood urea nitrogen (BUN) levels, and it can improve the renal damage in 1/3 NT + STZ-induced CRF mice with an increase in concentration (100, 300, and 500 mg/kg). In the immunohistochemical staining test, EtCE-EA can effectively reduce the expression of TGF-ß and α-SMA after induction according to the increase in the concentration (100 mg/kg, 300 mg/kg), thereby slowing down the degree of kidney damage. Our findings demonstrate that EtCE-EA could provide renal protection in diabetes nephropathy, possibly due to the decreased expression of transforming growth factor-ß1 and α-smooth muscle actin.

Anti-Inflammatory and Chondro-Protective Effects of Acidic Polysaccharide from Enteromorpha Prolifera in Experimental Models of Osteoarthritis In-Vitro and In-Vivo.

OBJECTIVE: Osteoarthritis (OA) progression has been shown to increase the expression of inflammatory cytokines in joints, leading to the destruction of cartilage matrix. Interleukin (IL)-1ß is a potent inflammatory cytokine associated with osteoarthritic synovial fluid. The protective effects of polysaccharides from Enteromorpha prolifera against acute hepatic injury was reported. DESIGN: In this study, we examined the effects of Enteromorpha polysaccharide extracts (EPEs) in the treatment of OA. The effects of the EPEs were assessed using an IL-1ß-stimulated SW1353 and SW982 cells. The expression levels of specific mRNA and proteins were evaluated using semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and western immunoblotting. An OA animal study involving C57BL/6J mice was also conducted to assess the effects on tactile sensitivity and anterior cruciate ligament transection (ACLT). RESULTS: Acidic polysaccharide extract (APE) was shown to significantly reduce cytokine and chemokine mRNA levels in IL-1ß-stimulated SW1353 and SW982 cells and attenuate the expression of proinflammatory cytokines and p38/AP-1 in SW1353 cells. APE was also shown to minimize the effect of osteolytic lesions in the knee joints of ACLT-induced osteoarthritic mice. CONCLUSIONS: APE is a potent inhibitor of joint degeneration associated with OA.

The effects of carbon monoxide releasing molecules on paraquat-induced pulmonary interstitial inflammation and fibrosis.

Paraquat, an herbicide used extensively worldwide, can cause severe toxicity in humans and animals, leading to irreversible, lethal lung fibrosis. The potential of CO-releasing molecules (CORMs), substances that release CO (Carbon monoxide) within animal tissues, for treating paraquat-induced ROS generation and inflammation is investigated here. Our results show that the fast CO releaser CORM-3 (4-20 µM) acts as a potential scavenger of free radicals and decreases fibrosis progression by inhibiting paraquat-induced overexpression of connective tissue growth factor and angiotensin II in MRC-5 cells. The slow CO releaser CORM-A1 (5 mg/kg) clearly decreased expression of the lung profibrogenic cytokines COX-2, TNF-α, and α-SMA and serum hydroxyproline, resulting in a lower mortality rate in paraquat-treated mice. Mice treated with higher-dose CORM-A1 (10 mg/kg) had relatively intact lung lobes and fewer fibrotic patches by gross observation, with less collagen deposition, mesangial matrix accumulation, and pulmonary fibrosis resulting from the mitigation of TGF-ß overexpression. In conclusion, our data demonstrate for the first time that CORM-A1 alleviated the development of the fibrotic process and improved survival rate in mice exposed to PQ, would be an attractive therapeutic approach to attenuate the progression of pulmonary fibrosis following PQ exposure.

[Differences in Patient Safety Reporting Attitudes and Knowledge Among Different Hospital Levels].

BACKGROUND: Establishing a positive reporting culture, which helps medical and healthcare workers learn from errors and reduce the risks of future adverse events, is essential to fostering a culture of patient safety. PURPOSE: The objectives of this study were to investigate the differences among the three levels of hospitals in terms of the knowledge and attitudes of hospital staff regarding the patient safety reporting system and to identify the potential factors affecting these differences. METHODS: This cross-sectional study was carried out in six hospitals, including two academic medical centers, two regional hospitals, and two district hospitals. The subjects were physicians, nurses, medical technicians, and administrative staffs. Data were collected using a patient safety reporting questionnaire. RESULTS: Three hundred and forty-eight participants were recruited, with 348 valid questionnaires returned (response rate: 100%). The average score for knowledge of patient safety reporting was 12.76 (total possible score: 14). Age, work position, and work experience were significantly associated with knowledge of patient safety reporting (p < .01). The patient safety reporting attitudes questionnaire comprised 21 items, each of which was scored using a five-point Likert scale. The mean score for each item was 3.92 ± 0.50. Gender, age, work position, work experience, and job discipline were significantly associated with attitude toward reporting (p < .01). The level of hospital was found to significantly impact attitudes toward patient safety reporting (p = .01), with participants working at medical centers scoring the highest. In addition, participants who were older and in more-senior positions scored higher and more positively for both knowledge and attitudes. CONCLUSIONS: The key factors to successfully fostering a strong patient safety reporting culture are staff security, a reliable reporting system, and a user-friendly interface. Improving attitudes toward reporting requires more resources and time than improving knowledge of reporting, which may be improved using education and promotion. Regional hospitals may invest more resources to enhance positive attitudes toward reporting and increase the willingness of staff to report.

Current port maintenance strategies are insufficient: View based on actual presentations of implanted ports.

Nursing staff play a crucial role in maintaining a functional port. Nursing guidelines recommend standard maintenance with 10 ml irrigation without consideration for variations among patients and individual nursing staff. The aim of this study is to identify the efficacy of the current maintenance strategy and analyze the correlation between complications and actual port presentations, based on disassembled intravenous ports after removal from patients. We attempt to organize the information and propose a definite maintenance strategy.After treatment completion, or due to complications, 434 implanted intravenous ports were removed from patients. All ports were deconstructed to observe their actual presentations and were then analyzed in conjunction with medical records. The correlation between complications and actual presentations was analyzed.From March 2012 to December 2017, 434 implanted intravenous ports were removed from oncology patients after completion of treatment or catheter related complications. From the view of maintenance related presentations, injection chamber blood clot was highly correlated with chemotherapy completion (P < .001) and malfunction (P = .005), while tip blood clot (P = .043) was related with chemotherapy completion and catheter fibrin (P = .015) was related to malfunction. From the view of structure related presentations, broken catheter integrity was correlated to chemotherapy completion (P = .007), fracture (P < .001), and malfunction (P = .008). Compression groove was related to chemotherapy completion (P = .03) and broken catheter at protruding stud was related to fracture (P = .04), while diaphragm rupture was correlated to chemotherapy completion (P = .048) and malfunction. (P < .001).Current port maintenance is insufficient for ideal port maintenance, whereby maintenance-related presentations, including tip clot, catheter fibrin, and injection chamber blood clot were identified. We propose a recommended maintenance strategy based on our findings. Structure-related presentations, including broken catheter integrity, broken catheter at protruding stud and diaphragm rupture were seen in patients with longer implantation period. Removal of the implanted port may be considered after 5 years if no disease relapse is noted.

Superior Vena Cava Port Catheter Tip Confirmation: Quantified Formula for Intravascular Catheter Length versus Anatomic Landmark Reference.

BACKGROUND: Adequate tip location is crucial for intravenous port implantation because it can minimize catheter-related complications. Adequate tip location cannot be observed directly and needs to be confirmed by imaging tools. A quantified intravascular catheter length formula has been proposed and we attempt to compare its clinical effectiveness with anatomic landmark references. METHODS: During the period from March 2012 to February 2013, 503 patients who received port implantation where implanted catheter length depended on carina level as confirmed by intraoperative fluoroscopy were assigned to Group A. From March 2013 to February 2014, 521 patients who received port implantation based on quantified intravascular catheter length formula were assigned to Group B. Clinical outcomes were compared. RESULTS: Catheter tip location of Group A, as revealed by intraoperative fluoroscopy and postoperative chest film, was 1.18 ± 0.51 and 1.1 ± 1.3 cm below carina, respectively. Catheter tip location of Group B, as revealed by intraoperative fluoroscopy and postoperative chest film, was 1.25 ± 1.05 and 1.05 ± 1.32 cm below carina, respectively. Similar catheter tip location was identified in both groups. The functional period of implanted ports, complication rate (3.58% and 2.53%), and incidence (0.049 and 0.0506 episodes/1,000 catheter days) were similar in both groups. CONCLUSIONS: The quantified intravascular catheter length formula can predict an adequate catheter length just as well as carina do and results in good catheter tip location. The formula could replace the clinical use of anatomic landmarks and serve as an easy tool for practitioners.

Recommended irrigation volume for an intravenous port: Ex vivo simulation study.

BACKGROUND: An intravenous port, which differs from a central venous catheter, has an injection chamber at the end of the catheter. This structural difference causes the irrigation flow pattern to be quite different from that of the central venous catheter. Furthermore, the intraluminal volume differs due to the size of the injection chamber and implanted catheter length. Hence, the ideal recommended irrigation volume varies because of differences in intraluminal volume, however, the recommended irrigation volume is 10 ml and may be a cause for reported port malfunctions. This study investigates the best irrigation volume for an intravenous port by simulating the clinical scenario ex-vivo to access its usefulness. MATERIALS AND METHODS: This study was composed of two tests. The irrigation volume test attempted to quantify the irrigation volume of an implanted port while the irrigation rate test attempted to simulate daily nursing practice in order to clarify the effect of irrigation flow. The human blood needed for the simulation was donated by volunteers and the total volume was 10 ml per test. The irrigation volume test was done by syringe pump with varying pre-set irrigation volume after the port and connected catheter were filled with volunteer blood. After irrigation with pre-set volume, the retained intraluminal solution was collected and quantified by Bradford assay in order to titrate the best irrigation volume. The irrigation rate test tried to simulate daily maintenance practice in different settings with the quantified irrigation volume as identified by the irrigation volume test. The retained intraluminal solution was collected and quantified by Bradford assay in order to confirm the efficacy of the quantified irrigation volume. RESULTS: In both SVC and IVC ports, we identified the twenty times the intravascular volume as sufficient for a complete wash out of the blood component in the irrigation volume test. The minimal irrigation volume for SVC and IVC port were 10 ml and 15.6 ml respectively. In irrigation rate test, the irrigation for SVC and IVC port was 10 and 20 ml, respectively, for the sake of preparation convenience. We not only identified the importance of preparation, i.e. irrigation of the extension line but also confirmed the efficacy of the recommended irrigation volume. CONCLUSION: The irrigation volume should be varied according to the intraluminal volume. Maintenance should be performed after the extension line has been irrigated. The recommended port irrigation volume for SVC and IVC route were 10 and 20 ml, respectively.

Initial experiences with a new design for a preattached intravenous port device.

All available conventional ports share a common design, including catheter, locking nut, and port body, and all share two sites of structural weakness. One site is the junction between the locking nut and the proximal end of the catheter. The other site is the catheter fixation site between the locking nut and the protruding stud of the connecting tube. To overcome these shortcomings, we designed a new type of intravenous port which combines the connecting tube into one piece. The aims of this study were to test the mechanical characteristics of the new design and assess its safety in animal study. The prototype of the preattached port was manufactured from biocompatible materials, including PEEK, silicone and polyurethane. All components were assembled with biocompatible glue and mechanical and safety tests were performed to determine the mechanical strength, and tissue reaction of surrounding soft tissue and entry vessels. The mechanical tests showed the new design would not lead to catheter fracture in the oscillation test. The traction test showed significant peak load (18.75 ± 3.29 vs. 26.61 ± 1.75 N; p = 0.036) because of the difference in catheter extension capacity (26.57 ± 4.28 vs. 47.93 ± 2.45 mm; p = 0.012). Significantly smaller endurable injection pressure was identified in the prototype. (90 ± 20 vs. 177.5± 9.48 psi; p = 0.01) The safety test showed good tolerance in beagle dogs and led to no intravascular thrombus and minimal reaction in surrounding tissues. The new prototype preattached port showed good mechanical strength and overcame two potential structural weakness points. The integrated fixation design not only reduced the dimensions of the port device but also provided a greater injection area compared to current designs. It did not cause intravascular thrombosis and produced minimal tissue reaction in surrounding soft tissue, as identified by autopsy. The new design of the fixation device could serve as the basis for the next generation of intravenous ports. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1017-1027, 2018.

Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration.

Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K+ ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP+ increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP+ insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD.

Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice.

BACKGROUND: Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects. METHODS: The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting. RESULTS: XYS/RTSES (300 µg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 µg/mL) or fluoxetine (30 µM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions. CONCLUSION: The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

Effects of Extract from Solid-State Fermented Cordyceps sinensis on Type 2 Diabetes Mellitus.

Diabetes mellitus is the most common chronic disease in the world, and a wide range of drugs, including Chinese herbs, have been evaluated for the treatment of associated metabolic disorders. This study investigated the potential hypoglycemic and renoprotective effects of an extract from the solid-state fermented mycelium of Cordyceps sinensis (CS). We employed the KK/HIJ diabetic mouse model, in which the mice were provided with a high-fat diet for 8 weeks to induce hyperglycemia, followed by the administration of CS or rosiglitazone for 4 consecutive weeks. Several parameters were evaluated, including changes in body weight, plasma lipid profiles, oral glucose tolerance tests, insulin tolerance tests, and plasma insulin concentrations. Our results show that the CS extract significantly elevated HDL/LDL ratios at 4 weeks and decreased body weight gain at 8 weeks. Interestingly, CS treatment did not lead to obvious improvements in hyperglycemia or resistance to insulin, while in vitro MTT assays indicated that CS protects pancreatic beta cells against the toxic effects of STZ. CS also enhanced renal NKA activity and reduced the accumulation of mesangial matrix and collagen deposition. In conclusion, CS extract can potentially preserve ß-cell function and offer renoprotection, which may afford a promising therapy for DM.

Applying HFMEA to prevent chemotherapy errors.

To evaluate risk and vulnerability in the chemotherapy process using a proactive risk analysis method. Healthcare failure mode and effect analysis (HFMEA) was adopted to identify potential chemotherapy process failures. A multidisciplinary team is formed to identify, evaluate, and prioritize potential failure modes based on a chemotherapy process flowchart. Subsequently, a decision tree is used to locate potential failure modes requiring urgent improvement. Finally, some recommended actions are generated and executed to eliminate possible risks. A total of 11 failure modes were identified with high hazard scores in both inpatient and outpatient processes. Computerized physician order entry was adopted to eliminate potential risks in chemotherapy processes. Chemotherapy prescription errors significantly decreased from 3.34% to 0.40%. Chemotherapy is regarded as a high-risk process. Multiple errors can occur during ordering, preparing, compounding, dispensing, and administering medications. Subsequently, these can lead to serious consequences. HFMEA is a useful tool to evaluate potential risk in healthcare processes.

Macrophage mediated anti-proliferation effects of Anthodia camphorata non-polysaccharide based extracts on human hepatoma cells.

It has been reported that medicinal mushrooms might induce different types of immune responses. Anthodia camphorata (A. camphorata) has attracted much attention for its therapeutic effects in treating hepatoma. We tested this anti-tumor effects using immunomodulation of macrophages and extracts of A. camphorata. We evaluated the anti-proliferation effects of various extracts of A. camphorata from fruiting bodies (AC-FB), mycelium of solid-state cultures (AC-SS), liquid-state cultures (AC-LS) and polyaccharide extracts from liquid-state cultures (AC-PS), and extracts of A. camphorata stimulated RAW 264.7 macrophage cell-conditioned mediums (MC-CMs). We measured cell proliferation and, did migration assays by cell cycle analysis and by observing apoptosis-related proteins (AKT, PARP-1, and NF-κB) and the mRNA expression of cytokines (TNF-α and IL-1ß) of macrophages in human hepatoma cell lines. Our results revealed that two of the extracts (AC-FB and AC-SS) had better anti-proliferation effects, implying an immunomodulatory role the macrophages might play. This outcome is consistent with findings that AC-FB and AC-SS increase mRNA expression of TNF-α and the corresponding expression of apoptosis-related proteins on activation of MC-CMs, while A. camphorata polysaccharides induce macrophage-derived anti-tumor activities in human hepatoma cells via IL-1ß and Akt activation. These results indicate that anti-tumor effects exerted by modulation of macrophage activation of A. camphorate may be influenced by the other constituents which (contained little or no polysaccharide) of A. camphorata.

Antitumor effect of BPR-DC-2, a novel synthetic cyclic cyanoguanidine derivative, involving the inhibition of MDR-1 expression and down-regulation of p-AKT and PARP-1 in lung cancer.

In our previous study, a series of novel cyclic cyanoguanidine compounds, eg. 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4- pyrimidinone derivatives have been successfully synthesized and showed remarkable cytotoxicity in several cancer cell lines. In this present study, it is our aim to screen more potential candidates among the cyclic pyridyl cyanoguanidine compounds (BPR-DC-1, 2, 3) by in vitro and in vivo studies for the therapy of lung cancer, alternatively. Our results showed that BPR-DC-2 significantly inhibited proliferation of tumor cells with an IC50 of 3.60 ± 1.27 and 14.81 ± 4.23 µM in human lung carcinoma cells, H69 and A549, respectively by the MTT assay at 48 hr; BPR-DC-2 also obviously suppressed the tumor proliferation and MDR-1 gene expression, even induced cell apoptosis in the ex vivo histocultured lung tumor. We further demonstrated that, in the nude mouse model of metastatic lung cancer, BPR-DC-2 could diminish the tumor mass, retard the progression of metastasis, and prolong the survival time. In addition, it was found that BPR-DC-2 exerted its anti-tumor effects through the inhibition of MDR-1 gene expression and down-regulation of tumor anti-apoptosis signals (activated p-AKT and over-expression of PARP-1) by western blotting analysis. In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic cyanoguanidine compounds, has proved its potential as an anti-tumor drug candidate in treating lung cancer.