Effectiveness of Problem-Based Learning on Development of Nursing Students' Critical Thinking Skills: A Systematic Review and Meta-analysis.

BACKGROUND: Problem-based learning (PBL) is a student-centered approach to teaching that has been applied in medical and nursing education. The effectiveness of PBL in promoting critical thinking in nursing students has been studied extensively with mixed results. PURPOSE: The meta-analysis aimed to investigate the impact of PBL interventions on critical thinking skills of nursing students. METHODS: PubMed, Embase, Cochrane, and CINAHL databases were electronically searched. Methodological quality was examined using the Newcastle-Ottawa Scale and version 2 of the Cochrane risk-of-bias tool. Data were analyzed with 95% confidence intervals based on random-effect models. RESULTS: Nineteen studies involving 1996 nursing students were included in the analysis. The results of the analysis demonstrated greater improvement in critical thinking skills compared with the control group (overall critical thinking scores: standardized mean difference [SMD] = 0.47, 95% CI = 0.33-0.61, P < .01). CONCLUSIONS: The meta-analysis indicates that PBL can help nursing students to improve their critical thinking.

Development of a novel multi-epitope vaccine based on capsid and envelope protein against Chikungunya virus.

Chikungunya virus (CHIKV), a type A virus borne by mosquitoes that can cause major clinical manifestations including rash, fever and debilitating arthritis, grown into a reemerging serious public health issue. Currently, there is no licensed therapy or vaccine available for CHIKV, although the most promising form of treatment appears to be immunotherapy. Neutralizing antibodies for CHIKV can provide high protection for all CHIKV strains, as well as other alphaviruses. Development of a protective vaccine may be an effective strategy to prevent the outbreak of CHIKV and provide protection for travelers. In this study, we designed a multi-epitope vaccine with a 543-amino-acid structure based on the E1, E2 and capsid proteins of CHIKV, including 6 CTL epitopes, 6 HTL epitopes, 12 linear B epitopes, along with the adjuvant ß-defensin III. All T-cell epitopes were docked with their corresponding MHC alleles to validate their effect on inducing immune responses, and the vaccine's sequence was proven to have acceptable physicochemical properties. Further, the developed vaccine was docked with TLR3 and TLR8, both of which play an important role in recognizing RNA viruses. Basic analyses of the docked complexes and molecular dynamic simulations revealed that the vaccine interacted strongly with TLRs. Immunological simulations indicated that the vaccine could induce both cellular and humoral immunity. Hopefully, this proposed vaccine structure can serve as a viable candidate against CHIKV infection.Communicated by Ramaswamy H. Sarma.

Design of a multi-epitope vaccine against six Nocardia species based on reverse vaccinology combined with immunoinformatics.

Background: Nocardia genus, a complex group of species classified to be aerobic actinomycete, can lead to severe concurrent infection as well as disseminated infection, typically in immunocompromised patients. With the expansion of the susceptible population, the incidence of Nocardia has been gradually growing, accompanied by increased resistance of the pathogen to existing therapeutics. However, there is no effective vaccine against this pathogen yet. In this study, a multi-epitope vaccine was designed against the Nocardia infection using reverse vaccinology combined with immunoinformatics approaches. Methods: First, the proteomes of 6 Nocardia subspecies Nocardia subspecies (Nocardia farcinica, Nocardia cyriacigeorgica, Nocardia abscessus, Nocardia otitidiscaviarum, Nocardia brasiliensis and Nocardia nova) were download NCBI (National Center for Biotechnology Information) database on May 1st, 2022 for the target proteins selection. The essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome proteins were selected for epitope identification. The shortlisted T-cell and B-cell epitopes were fused with appropriate adjuvants and linkers to construct vaccines. The physicochemical properties of the designed vaccine were predicted using multiple online servers. The Molecular docking and molecular dynamics (MD) simulation were performed to understand the binding pattern and binding stability between the vaccine candidate and Toll-like receptors (TLRs). The immunogenicity of the designed vaccines was evaluated via immune simulation. Results: 3 proteins that are essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome were selected from 218 complete proteome sequences of the 6 Nocardia subspecies epitope identification. After screening, only 4 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes that were antigenic, non-allergenic, and non-toxic were included in the final vaccine construct. The results of molecular docking and MD simulation showed that the vaccine candidate has a strong affinity for TLR2 and TLR4 of the host and the vaccine-TLR complexes were dynamically stable in the natural environment. The results of the immune simulation indicated that the designed vaccine had the potential to induce strong protective immune responses in the host. The codon optimization and cloned analysis showed that the vaccine was available for mass production. Conclusion: The designed vaccine has the potential to stimulate long-lasting immunity in the host, but further studies are required to validate its safety and efficacy.

Development of a novel circular mRNA vaccine of six protein combinations against Staphylococcus aureus.

Staphylococcus aureus is an extraordinarily versatile pathogen, which is currently the most common cause of nosocomial and community infections. Considering that increased antibiotic resistance may hasten the spread of S. aureus, developing an effective vaccine can possibly aid in its control. The RNA vaccine coding immunodominance epitopes from bacteria provide a potential method to induce T and B cell immune responses by translating them into cells. Furthermore, using bioinformatics to create circular RNA vaccines can ensure that the translation of the vaccine is potent and durable. In this study, 7 cytotoxic T lymphocyte (CTL) epitopes, 4 helper T lymphocyte (HTL) epitopes, and 15 B cell epitopes from 6 proteins that are closely associated with the S. aureus virulence and invasion and critical to natural immune responses were mapped. To verify their interactions, all epitopes were docked with the corresponding MHC alleles. The final vaccine was composed of 26 epitopes and the adjuvant ß-defencin, and a disulfide bond was also introduced to improve its stability. After the prediction of structure and characteristics, the developed vaccine was docked with TLR2 and TLR4, which induce immunological responses in S. aureus infection. According to the molecular dynamic simulation, the vaccine might interact strongly with TLRs. Meanwhile, it performed well in immunological simulation and population coverage prediction. Finally, the vaccine was converted into a circular RNA using a series of helper sequences to aid in vaccine circulation translation. Hopefully, this proposed structure will be proven to serve a viable vaccine against S. aureus.Communicated by Ramaswamy H. Sarma.

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus.

Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants ß-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine's efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.

Identification of Molecular Subtypes and a Novel Prognostic Model of Sepsis Based on Ferroptosis-Associated Gene Signature.

Ferroptosis has recently been associated with immunological changes in sepsis. However, the clinical significance of ferroptosis-associated genes (FAGs) remains unknown. In this paper, a FAG-based prognostic model was constructed for sepsis patients using an integrated machine learning approach. The prognosis model was composed of 14 FAGs that classify the patients as high or low risk. Based on immunological study, it was found that the immune status differed between the high-risk and low-risk clusters. Cox regression analysis revealed that FAGs were independent risk factors for the overall survival of sepsis patients. ROC curves and nomograms revealed that the FAG-based model was robust for prognosis prediction. Lastly, NEDD4L was identified from the 14 FAGs as a potential hub gene for sepsis prediction.

MiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis.

Alveolar epithelial cell damage is an important determinant of the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms of alveolar epithelial death during the development of ALI/ARDS remain unclear. In this study, we explore the role of miR-29a-3p in ALI/ARDS and its molecular mechanism. Plasma samples were collected from healthy controls and ARDS patients. Mice were intratracheally instilled with lipopolysaccharide (LPS) to establish acute lung injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, cell viability assay, quantitative real-time polymerase chain reaction, and western blotting were performed. We found that miR-29a-3p was down-regulated in plasma of ARDS patients and lung tissue of ALI model mice, and miR-29a-3p agomir injection down-regulated the levels of the inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the lungs, reducing alveolar epithelial cell PANoptosis as evaluated by the downregulation of Z-DNA binding protein 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, and mixed lineage kinase domain-like protein (MLKL), ultimately improving lung injury in the ALI model mice. Mechanism studies demonstrated that the knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of miR-29a-3p and reduced miR-29a-3p expression. Our findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.

Enrichment of heavy metals from spent printed circuit boards by microwave pyrolysis.

This study reports the enrichment behaviors of heavy metals, including copper, tin, lead and zinc, in the process of microwave pyrolysis of spent printed circuit boards (SPCBs). The SPCB had good microwave absorptivity. Under the optimal conditions of microwave power of 700 W, pyrolysis temperature of 400 °C, dwell time of 5 min, N2 gas flow rate of 1.2 L/min, and load mass of 5 g, the yield of pyrolyzed SPCB was 79.16%. The contents of copper, tin, lead, and zinc in the pyrolyzed SPCB were increased to 28.52 wt%, 7.15 wt%, 1.31 wt%, and 1.13 wt%, respectively, with the corresponding retention percentages of 99.98%, 85.89%, 92.59% and 82.06%. The loss of metals was attributed to volatilization of the elements, which was affected by metal discharge due to excitation of electrons in the metals under microwave irradiation. Little copper loss was found because of the difficult reaction between copper and hydrogen bromide and the very high temperature required by the volatilization of copper. Tin, lead and zinc were mainly volatilized in the form of their metal bromides, including SnBr4, ZnBr2, and PbBr2. By controlling the pyrolysis conditions and metal discharge induced in the microwave field, the metals could be effectively enriched for subsequent treatment with high efficiency.

Mn-vacancy birnessite for photo-assisted elimination of formaldehyde at ambient condition.

Visible light-assisted catalysis has recently attracted considerable attention because it is efficient, cost effective, and does not cause indoor air pollution. Several birnessite-type MnO2 catalysts with different numbers of manganese vacancies (MVs) were synthesized in this study and used for photo-assisted catalytic oxidation of HCHO. Under visible light irradiation, MVs act as trapping centers to accelerate electrons transport and produce abundant reactive radicals to boost the activation of molecular oxygen, thereby improving the catalytic HCHO oxidation. The birnessite with the highest number of MVs exhibits remarkable oxidation activity with 80 ppm of HCHO (42% HCHO conversion was attained at ambient temperature) and a corresponding gas hourly space velocity (GHSV) of 60 L/(g·h) in a dynamic experiment. Moreover, it mineralizes 80 ppm of HCHO within 160 min in a static experiment, whereas it only takes 90 min under the same conditions with the visible light irradiation. The activity factor of birnessite with the highest MV content under visible light irradiation is 2.2 times that observed under dark conditions. Overall, this study elucidates the photothermal catalytic oxidation of HCHO, and concludes that the birnessite comprising MVs is a promising material for air purification applications.

Transition metal ions-modified birnessite toward highly efficiency photocatalytic formaldehyde oxidation under visible light irradiation.

Accelerating the interfacial charge transfer process (ICTS) of the catalysts can immensely improve the photocatalytic efficiency. Doping transition metal ions not only promote the ICTS, but also boost multielectron reduction reactions of oxygen. Herein, birnessite-type MnO2 have been modified by different transition metal ions (TM = Zn2+, Cu2+, and Fe3+) in this work. Post-doping, Fe-Birnessite was featured by the highest photocatalytic HCHO oxidation activity with 80 ppm of HCHO which presented complete removal of HCHO for 80 min, while K-, Cu-, and Zn-Birnessite took 105, 135, and 170 min, respectively. In detail, the photoexcited electrons were caught by Fe (III) and then generated Fe (II),which could continue to capture photoexcited electrons to produce Fe (I) under visible light; on the other hand, the Fe (I) could be oxidized by O2 to obtain Fe (II) and then recover to Fe (III). This process tremendously improved the ICTS.

Association of thyroid hormones and thyroid-stimulating hormone with mortality in adults admitted to the intensive care unit: A systematic review and meta-analysis.

BACKGROUND: Thyroid hormones (THs) and thyroid-stimulating hormone (TSH) seem to show high potential in predicting the clinical death outcome of patients admitted to the intensive care unit (ICU). However, diverse studies on this topic are conflicting. METHODS: A search was conducted by two investigators involved in this research in the PubMed, Embase, and Cochrane databases (all last launched on July 12, 2021). The quality of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). Subgroup analyses were performed to determine the sources of heterogeneity. Sensitivity and publication bias analyses were also assessed. RESULTS: A total of 27 studies (4970 participants) were included based on the eligibility criteria. Compared with survivors, nonsurvivors were found to have lower levels of THs (T3, T4, fT3, and fT4), whereas no significant difference was found in TSH levels (13 studies for T3: standardized mean differences [SMD], -0.78; 95% CI, -1.36 to -0.20; I2 = 96%; p = 0.008; 11 studies for T4: SMD = -0.79; 95% CI, -1.31 to -0.28; I2 =95%; p = 0.0002; 14 studies for fT3: SMD = -0.76; 95% CI, -1.21 to -0.32; I2 = 95%; p = 0.0008; 17 studies for fT4: SMD = -0.60; 95% CI, -0.99 to -0.22; I2 = 95%; p = 0.002; 20 studies for TSH: SMD = 0.00; 93% CI, -0.29 to 0.29; I2 = 93%; p = 0.98). CONCLUSION: Nonsurvivors were associated with lower levels of THs (T3, T4, fT3, and fT4) than survivors. THs show great application potential in predicting ICU patients' death outcomes and improving already widely used prognostic scores in the ICU (ie, Acute Physiological and Chronic Health Evaluation [APACHE] II and Therapeutic Intervention Scoring System).

Importance of water content in birnessite-type MnO2 catalysts for HCHO oxidation: Mechanistic details and DFT analysis.

Water is featured in an indispensable role during the process of catalytic oxidation of HCHO. In this work, a rich water-containing birnessite-type MnO2 was synthesized, and its water content was adjusted through calcination. Phase structure and texture properties of the prepared birnessite were characterized. It was revealed that three types of water (namely absorbed water, molecular water, and structural hydroxyl) existed in birnessite. With the loss of water content, the interlayer distance of samples had decreased which changed the structure of birnessite to cryptomelane. This converted the morphology from an initial layered shape to a rod-like shape. Besides, the underlying mechanism for this effect on HCHO catalytic oxidation was elucidated. Results indicated that hydroxyl groups could slowly and sequentially oxidize HCHO to DOM, formate, and carbonate species. The hydroxyl groups also promoted the formation of oxygen vacancy which could activate O2 to O- 2 and O-. The hydroxyl groups which were consumed had originally been supplied by the reaction between O- 2, O-, and H2O (absorbed and interlayer water in birnessite) which was then replenished from air stream. Clearly, water is favorable to the catalytic reaction. It is the main reason why birnessite can continuously decompose HCHO.

Toward environmentally friendly direct reduced iron production: A novel route of comprehensive utilization of blast furnace dust and electric arc furnace dust.

In this study, a novel method for producing direct reduced iron (DRI) powders based on microwave-assisted self-reduction of core-shell composite pellets composed of blast furnace (BF) dust and hazardous electric arc furnace (EAF) dust followed by magnetic separation was reported. The proper core-shell structure of the composite pellets was designed according to the rule of impedance matching and properties of BF dust and EAF dust by adjusting the thickness of shell (i.e., thickness of impedance matching layer) via controlling the C/O molar ratio of the raw materials from 0.55 to 0.70. The results showed that the EAF dust with high content of CaO was beneficial to the mechanical strength of green, dried, and metallized pellets (collected after reduction), while the BF dust with high content of carbon enabled sufficient microwave-assisted reduction of the pellets, facilitating subsequent magnetic separation and also the removal of zinc from EAF dust. By reduction of the core-shell BF dust-EAF dust composite pellets with the C/O molar ratio of 0.65 at 1050 °C for 15 min, the resulting metallized pellets showed superior reduction and magnetic separation indexes with higher removal percentages of zinc and lead, in comparison with conventional metallized pellets. The DRI powders obtained after magnetic separation had total iron content of 91.2 wt%, iron metallization degree of 95.8%, yield of 68.1%, and iron recovery of 88.0%. This study provided a good example for efficient and environmentally friendly comprehensive utilization of typical and hazardous wastes in the iron and steel industry.

Partial substitution of anthracite for coke breeze in iron ore sintering.

In the sintering of iron ores, the partial substitution of anthracite for coke breeze has been considered to be an effective way of reducing pollutant emissions and production cost. In this study, the basic characteristics of anthracite and coke breeze were compared and the sintering performance at different substitution ratios of anthracite for coke breeze was investigated. The porosity of anthracite is lower than that of coke breeze, but its density and combustion reactivity are higher. The substitution of anthracite for coke breeze has no influence on the granulation effect of the sintering blend. As the anthracite proportion increased, the sintering speed and productivity increased and the sintering yield and tumbler index decreased. As the substitution ratio increased from 0 to 60%, the melting temperature duration and the melt quantity index decreased from 2.59 to 2.03 min and from 3218.28 to 2405.75 °C·min, respectively, leading to insufficient sintering mineralization and bad sintering indexes. For an anthracite substitution ratio of 40%, the sintering speed, sintering productivity, sintering yield and tumbler index were 22.34 mm min-1, 1.49 t·(m2 h)-1, 71.65% and 63.59%, respectively, which entirely satisfies the production requirements. Furthermore, hematite (Fe2O3), calcium ferrite (CaO-Fe2O3), and compound calcium ferrite (CaO-SiO2-Fe2O3) were the major mineral phases, which were embedded with an interwoven structure.

DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors.

Objective: Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer (NSCLC), but no direct Mcl-1 inhibitor is currently available for clinical use. Thus, novel therapeutic strategies are urgently needed to target Mcl-1 and sensitize the anti-NSCLC activity of Bcl-2 inhibitors. Methods: Cell proliferation was measured using sulforhodamine B and colony formation assays, and apoptosis was detected with Annexin V-FITC staining. Gene expression was manipulated using siRNAs and plasmids. Real-time PCR and Western blot were used to measure mRNA and protein levels. Immunoprecipitation and immunofluorescence were used to analyze co-localization of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and Mcl-1. Results: Suppression of DYRK1A resulted in reduced Mcl-1 expression in NSCLC cells, whereas overexpression of DYRK1A significantly increased Mcl-1 expression. Suppression of DYRK1A did not alter Mcl-1 mRNA levels, but did result in an accelerated degradation of Mcl-1 protein in NSCLC cells. Furthermore, DYRK1A mediated proteasome-dependent degradation of Mcl-1 in NSCLC cells, and DYRK1A co-localized with Mcl-1 in NSCLC cells and was co-expressed with Mcl-1 in tumor samples from lung cancer patients, suggesting that Mcl-1 may be a novel DYRK1A substrate. We showed that combined therapy with harmine and Bcl-2 antagonists significantly inhibited cell proliferation and induced apoptosis in NSCLC cell lines as well as primary NSCLC cells. Conclusions: Mcl-1 is a novel DYRK1A substrate, and the role of DYRK1A in promoting Mcl-1 stability makes it an attractive target for decreasing Bcl-2 inhibitor resistance.

Recovering Magnesium from Ferronickel Slag by Vacuum Reduction: Thermodynamic Analysis and Experimental Verification.

The feasibility of recovering magnesium from ferronickel slag by vacuum reduction was evaluated. The thermodynamic calculations indicated that the magnesia in slag can be reduced to gaseous magnesium by Si, FeSi, Al, and C, with the minimum reduction temperatures of 2324, 2530, 1678, and 2580 K at 100 000 Pa, respectively. As the system pressure decreases, the minimum reduction temperatures decline significantly. Si maintains the minimum reduction temperature of 1585-1673 K at the atmospheric pressure of 10-100 Pa, acting as a suitable reducing agent for recovering magnesium. To verify the findings, preliminary vacuum reduction experiments, in which CaO was added to eliminate the adverse impact of SiO2 in slag, were carried out. By reducing slag with additions of 50 wt % Si and 30 wt % CaO at 1573 K for 3 h at 10 Pa, the recovery of magnesium reached 97.74%.

DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild-type NSCLC cells to AZD9291.

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR-sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild-type EGFR remains modest. We showed that DYRK1A repression could enhance the anti-cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild-type NSCLC cells. In addition, harmine could enhance the anti-NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti-cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild-type NSCLC patients.

Harmine suppresses the proliferation of pancreatic cancer cells and sensitizes pancreatic cancer to gemcitabine treatment.

PURPOSE: Pancreatic carcinoma is one of the most deadliest types of cancer, and relatively insensitive to the currently available chemotherapy. Thus, the discovery of novel therapeutic agents to prolong the survival times of patients with pancreatic cancer is urgently required. METHODS: Cell proliferation was assessed using the sulforhodamine B and cell clone formation assay, apoptosis was analyzed through Annexin V/PI staining, analysis of cell cycle distribution was determined by PI staining, and the expression of proteins was detected via Western blotting. RESULTS: Our data showed that harmine exerted an anti-proliferative effect and cell cycle arrest at G2/M in pancreatic cancer cells. Meanwhile, harmine plus gemcitabine showed strong synergy in inhibiting the proliferation of pancreatic cancer cells. Furthermore, harmine induced apoptosis and enhanced the gemcitabine-induced apoptosis in pancreatic cancer cells. The AKT/mTOR pathway is involved in mechanisms of gemcitabine resistance in pancreatic cancer cells, our data demonstrated that harmine plus gemcitabine significantly suppressed the AKT/mTOR signaling pathway. CONCLUSION: Harmine may be a potential candidate for the treatment of pancreatic cancer. Morever, the combination of harmine with gemcitabine appears to be an attractive option for the treatment of patients with pancreatic cancer.

BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3ß activation.

Hepatocellular carcinoma (HCC) is associated with some of the highest cancer-associated mortality rates. Histone deacetylase (HDAC) inhibitors anti-HCC activities have been shown to promote Snail-induced metastasis. In the present study, it was shown that BAY 87-2243, a hypoxia-inducible transcription factor-1α inhibitor, could enhance the anti-HCC effects of HDAC inhibitors, including trichostatin A and vorinostat. In addition, BAY 87-2243 plus HDAC inhibitors exhibited synergistic cytotoxicity and induced significant cell death in Hep3B cells. Additionally, BAY 87-2243 combined with HDAC inhibitors-treated Hep3B cells formed fewer and smaller colonies as compared with either the control or single agent-treated cells. Furthermore, glycogen synthase kinase-3ß might be involved in the enhanced cell death induced by BAY 87-2243 plus HDAC inhibitors. The present data also indicated that BAY 87-2243 combined with HDAC inhibitors could suppress the migration of Hep3B cells, and BAY 87-2243 could reverse the HDAC inhibitor-induced Snail activation in Hep3B cells. In conclusion, BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy.