Knock down of APE1 suppressed gastric cancer metastasis via improving immune disorders caused by myeloid-derived suppressor cells.

Gastric cancer is a highly immunogenic malignancy. Immune tolerance facilitated by myeloid-derived suppressor cells (MDSCs) has been implicated in gastric cancer resistance mechanisms. The potential role of APE1 in regulating gastric cancer metastasis by targeting MDSCs remains uncertain. In this study, the plasmid Plxpsp-mGM-CSF was used to induce high expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in GES-1 cells. For tumor transplantation experiments, AGS, AGS+GM-CSF and AGS+GM-CSF-siAPE1 cell lines were established by transfection, followed by subcutaneous implantation of tumor cells. MDSCs, Treg cells, IgG, CD3 and CD8 levels were assessed. Transfection with siAPE1 significantly inhibited tumor growth compared to the AGS+GM-CSF group. APE1 gene knockdown modulated the immune system in gastric cancer mice, characterized by a decrease in MDSCs and an increase in Treg cells, IgG, CD3 and CD8. In addition, APE1 gene knockdown resulted in decreased levels of pro-MDSC cytokines (HGF, CCL5, IL-6, CCL12). Furthermore, APE1 gene knockdown inhibited proliferation, migration and invasion of AGS and MKN45 cells. AGS-GM-CSF cell transplantation increased MDSC levels and accelerated tumor growth, whereas APE1 knockdown reduced MDSC levels, inhibited tumor growth and attenuated inflammatory infiltration in gastric cancer tissues. Strategies targeting the APE1/MDSC axis offer a promising approach to the prevention and treatment of gastric cancer, providing new insights into its management.

A systematic review of cost-effectiveness analysis of different screening strategies for familial hypercholesterolemia.

AIMS: Diagnosis rate of familial hypercholesterolemia (FH) remained less than 10 % globally and the economic evaluation results of different FH screening strategies varied. This study aimed to systematically review the methodology and results of cost effectiveness analysis (CEA) of FH screening, which will provide evidence support for health-related decision-making. METHODS: The Medline/PubMed, Embase, Cochrane Library, Web of science, National Health Service Economic Evaluation Database (NHSEED) and CEA Registry databases were electronically searched to collect full economic evaluation from the establishment of the databases to June 30, 2022. The quality of included studies was evaluated by the Consolidated Health Economic Evaluation Reporting Standards statement 2022 (CHEERS 2022) checklist. RESULTS: Among 232 retrieved studies, 18 economic evaluations were included and all of them are from developed countries, with an average quality score of 0.73. The decision tree model and/or Markov model were constructed by thirteen articles (72 %). Twelve studies (67 %) adopted the healthcare perspective and the lifetime horizon to compare the costs and health outcome of different screening strategies. The results of eight studies indicated that cascade screening was a cost-effective strategy compared with no screening, which was more pronounced in younger adults. Universal screening in young adults aged 16 years or 18-40 years (n=3) and in children aged 1-2 years combined with reverse cascade screening (n=3) are both cost-effective. The probability of being cost-effective for cascade screening (n=6) and universal screening (n=1) of young aged 18-40 years were greater than 95 %. CONCLUSIONS: Our review demonstrated the economic advantages of cascade screening, universal screening of young adults, and universal screening of newborns combined with reverse cascade screening. Further health economic evaluation is needed in children and in low- and middle-income countries.

Machine learning algorithm integrates bulk and single-cell transcriptome sequencing to reveal immune-related personalized therapy prediction features for pancreatic cancer.

Pancreatic cancer (PC) is a digestive malignancy with worse overall survival. Tumor immune environment (TIME) alters the progression and proliferation of various solid tumors. Hence, we aimed to detect the TIME-related classifier to facilitate the personalized treatment of PC. Based on the 1612 immune-related genes (IRGs), we classified patients into Immune_rich and Immune_desert subgroups via consensus clustering. Patients in distinct subtypes exhibited a difference in sensitivity to immune checkpoint blockers (ICB). Next, the immune-related signature (IRS) model was established based on 8 IRGs (SYT12, TNNT1, TRIM46, SMPD3, ANLN, AFF3, CXCL9 and RP1L1) and validated its predictive efficiency in multiple cohorts. RT-qPCR experiments demonstrated the differential expression of 8 IRGs between tumor and normal cell lines. Patients who gained lower IRS score tended to be more sensitive to chemotherapy and immunotherapy, and obtained better overall survival compared to those with higher IRS scores. Moreover, scRNA-seq analysis revealed that fibroblast and ductal cells might affect malignant tumor cells via MIF-(CD74+CD44) and SPP1-CD44 axis. Eventually, we identified eight therapeutic targets and one agent for IRS high patients. Our study screened out the specific regulation pattern of TIME in PC, and shed light on the precise treatment of PC.

Modelling the impact of treatment adherence on the transmission of HIV drug resistance.

INTRODUCTION: A lower adherence rate (percentage of individuals taking drugs as prescribed) to ART may increase the risk of emergence and transmission of HIV drug resistance, decrease treatment efficacy, and increase mortality rate. Exploring the impact of ART adherence on the transmission of drug resistance could provide insights in controlling the HIV epidemic. METHODS: We proposed a dynamic transmission model incorporating the CD4 cell count-dependent rates of diagnosis, treatment and adherence with transmitted drug resistance (TDR) and acquired drug resistance. This model was calibrated and validated by 2008-2018 HIV/AIDS surveillance data and prevalence of TDR among newly diagnosed treatment-naive individuals from Guangxi, China, respectively. We aimed to identify the impact of adherence on drug resistance and deaths during expanding ART. RESULTS: In the base case (ART at 90% adherence and 79% coverage), we projected the cumulative total new infections, new drug-resistant infections, and HIV-related deaths between 2022 and 2050 would be 420 539, 34 751 and 321 671. Increasing coverage to 95% would reduce the above total new infections (deaths) by 18.85% (15.75%). Reducing adherence to below 57.08% (40.84%) would offset these benefits of increasing coverage to 95% in reducing infections (deaths). Every 10% decrease in adherence would need 5.07% (3.62%) increase in coverage to avoid an increase in infections (deaths). Increasing coverage to 95% with 90% (80%) adherence would increase the above drug-resistant infections by 11.66% (32.98%). CONCLUSIONS: A decrease in adherence might offset the benefits of ART expansion and exacerbate the transmission of drug resistance. Ensuring treated patients' adherence might be as important as expanding ART to untreated individuals.

Instant Coffee Is Negatively Associated with Telomere Length: Finding from Observational and Mendelian Randomization Analyses of UK Biobank.

Telomere length, as a biomarker of accelerated aging, is closely related to many chronic diseases. We aimed to explore the association between coffee consumption and telomere length. Our study included 468,924 participants from the UK Biobank. Multivariate linear models (observational analyses) were conducted to evaluate the associations of coffee intake, instant coffee intake, and filtered coffee intake with telomere length. In addition, we evaluated the causality of these associations in Mendelian randomization (MR) analyses by four methods (inverse-variance weighted (IVW), MR pleiotropy residual sum and outlier (MR-PRESSO), MR-Egger, and weighted median). Observational analyses indicated that coffee intake and instant coffee intake were negatively correlated with telomere length, which was equal to 0.12 year of age-related decrease in telomere length for each additional cup of coffee intake (p < 0.001), and 0.38 year of age-related decrease in telomere length for each additional cup of instant coffee intake (p < 0.001), respectively. There was no significant correlation between filtered coffee and telomere length (p = 0.862). Mendelian randomization analyses supported the results of observational analyses. Coffee intake was found to have a causal effect on telomere length through weighted median analysis (p = 0.022), and instant coffee intake had a causal effect on telomere length through IVW analysis (p = 0.019) and MR-PRESSO analysis (p = 0.028). No causal relationship was found between filtered coffee intake and telomere length (p > 0.05). Coffee intake, particularly instant coffee, was found to have an important role in shortening telomere length.

Mammography diagnosis of breast cancer screening through machine learning: a systematic review and meta-analysis.

Breast cancer was the fourth leading cause of cancer-related death worldwide, and early mammography screening could decrease the breast cancer mortality. Artificial intelligence (AI)-assisted diagnose system based on machine learning (ML) methods can help improve the screening accuracy and efficacy. This study aimed to systematically review and make a meta-analysis on the diagnostic accuracy of mammography diagnosis of breast cancer through various ML methods. Springer Link, Science Direct (Elsevier), IEEE Xplore, PubMed and Web of Science were searched for relevant studies published from January 2000 to September 2021. The study was registered with the PROSPERO International Prospective Register of Systematic Reviews (protocol no. CRD42021284227). A Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess the included studies, and reporting was evaluated using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The pooled summary estimates for sensitivity, specificity, the area under the receiver operating characteristic curve (AUC) for three ML methods (convolutional neural network [CNN], artificial neural network [ANN], support vector machine [SVM]) were calculated. A total of 32 studies with 23,804 images were included in the meta-analysis. The overall pooled estimate for sensitivity, specificity and AUC was 0.914 [95% CI 0.868-0.945], 0.916 [95% CI 0.873-0.945] and 0.945 for mammography diagnosis of breast cancer through three ML methods. The pooled sensitivity, specificity and AUC of CNN were 0.961 [95% CI 0.886-0.988], 0.950 [95% CI 0.924-0.967] and 0.974. The pooled sensitivity, specificity and AUC of ANN were 0.837 [95% CI 0.772-0.886], 0.894 [95% CI 0.764-0.957] and 0.881. The pooled sensitivity, specificity and AUC of SVM were 0.889 [95% CI 0.807-0.939], 0.843 [95% CI 0.724-0.916] and 0.913. Machine learning methods (especially CNN) show excellent performance in mammography diagnosis of breast cancer screening based on retrospective studies. More rigorous prospective studies are needed to evaluate the longitudinal performance of AI.

An abscopal effect in a gastric cancer patient treated with combined chemoimmunotherapy and palliative radiotherapy.

The prognosis of advanced gastric cancer remains poor. Palliative radiotherapy has been utilized to palliate bleeding in unresectable gastric cancer. Recent studies have described that a systemic immune response may be induced by local radiotherapy to the primary tumor lesion. Here we report a rare case of an abscopal effect in a patient with inoperable gastric cancer combined with tumor hemorrhage. A short course of radiotherapy was performed to palliate bleeding; additionally, the patient was treated with chemotherapy and immunotherapy. Complete response was achieved in the lung metastasis lesion. The observed abscopal effect suggests that there may be a synergistic effect between immunotherapy and radiotherapy. This case report supports the combination of immunotherapy and radiotherapy in patients with advanced gastric cancer.

Our case report suggests the potential benefits of immunotherapy combined with palliative radiotherapy in advanced gastric cancer. Metastatic lesions of cancer patients could obtain a treatment response by local radiotherapy to the primary tumor and systemic immunotherapy. The results indicate a synergistic effect of immunotherapy and radiotherapy in activating an antitumor immune response.

The miR-532-E2F1 feedback loop contributes to gastric cancer progression.

Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy.

MicroRNA-656-3p inhibits colorectal cancer cell migration, invasion, and chemo-resistance by targeting sphingosine-1-phosphate phosphatase 1.

Colorectal cancer presents high rates of recurrence and metastasis, and the occurrence and progression and mechanism of its invasion and metastasis are not fully understood. The expression of miR-656-3p in patient samples and 10 cell lines were measured. Bioinformatic databases were used to predict miRNAs. Protein expressions were examined using Western blot. Transwell assay was used to measure cell migration and invasion. Transplanted tumor model in nude mice was established. Removal of the miR-656-3p by specific knocking-down of this gene promoted the chemo-resistance of colorectal cancer cells. Critically, we identified sphingosine-1-phosphate phosphatase 1 (SGPP1) as a downsteam target of the miR-656-3p, which we first obtained from 199 potential target genes from Targetscan, 200 genes from miRDB and 200 genes from DIANA, respectively. Then, we identified the interaction between SGPP1 and the miR-656-3p on 3' UTR of SGPP1 gene. Knockdown of SGPP1 greatly suppressed the tumor growth in vivo and epithelial mesenchymal transition process. miR-656-3p could regulate cell proliferation and chemoresistance in the colorectal cancer that associate to downstream target with SGPP1. Along with its downstream molecule, we would like to predict that the SGPP1 associated miR-656-3p could be used to develop early for early diagnostics for CRC oncogenesis.

A novel role of miR-326 in colorectal carcinoma by regulating E2F1 expression.

PURPOSE: Colorectal carcinoma (CRC) ranks third in incidence but second in mortality worldwide, ascertaining the pathogenesis of CRC is crucial for its treatment. Accumulating studies have shown that E2F1 is a key regulator in CRC progression, which regulates the transcription of genes engaged in DNA replication, mitosis and survival of cancer patients, however, the mechanism of these processes is not fully elucidated. METHODS: Here, we determined E2F1 expression in clinical CRC specimens by TCGA database analysis, Microarray immunohistochemical technique and Western blot, respectively. The expression of E2F1 was elevated in CRC tumor tissues, and the patients' total survival time was associated with the level of E2F1. Then the prediction software and meta-analysis were used to predict the miRNAs targeting E2F1. RT-qPCR, TCGA analysis and in situ hybridization experiments were utilized to determine the decreased miR-326 expression in CRC tumor tissues. Luciferase and Western blot assays determined that miR-326 directly targeted E2F1 in CRC cells. Next, CCK8, flow cytometry, Transwell and wound healing assays were used to determine the biological function of miR-326-E2F1 axis in vitro. RESULTS: miR-326 overexpression significantly inhibited the viability, invasion and migration and promoted the apoptosis of CRC cells, but overexpression of both E2F1 and miR-326 in turn increased cell viability, invasion and migration and decreased cell apoptosis. CONCLUSIONS: This study demonstrates the significant roles of miR-326-E2F1 in CRC progression and may represent a potential target for CRC therapy.

Distinct metabolite profiles of adiposity indices and their relationships with habitual diet in young adults.

BACKGROUND AND AIMS: Obesity is characterized as overall or regional adiposity accumulation. However, the metabolic status underlying fat accumulation was not well understood. We sought to identify metabolite profiles based on their correlations with body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and visceral adiposity index (VAI) in young Chinese adults (19-37 years old), and their associations with dietary consumption were also explored. METHODS AND RESULTS: A total of 86 plasma samples were analyzed using untargeted lipidomics and metabolomics approaches. Metabolite profiles of adiposity indices were identified using random forest modelling. Ridge regression was used to generate metabolite scores. Overall, 30, 46, 30, and 20 metabolites correlated with BMI, BFP, WC, and VAI, respectively, which resulted in metabolite scores for each index. Top three enriched categories of the identified metabolites were glycerophospholipids, glycerolipids, and sphingolipids, with some specific metabolites (such as phosphatidylserine (37:2), phatidylethanolamine (42:4), and ceramide (40:0)) exclusively associated with overall adiposity, and some other metabolites exclusively associated with abdominal adiposity indices, e.g., triradylglycerol (45:0, 52:4, and 35:0) and diacylglycerol (38:4, 36:3, and 36:5). Moreover, metabolite scores were negatively associated with the intake of food rich in protein or fiber, while they were positively associated with food rich in carbohydrate, with similar results for adiposity indices. CONCLUSION: We observed unique metabolite profiles of regional or overall fat deposition in young adults. Glycerophospholipids, glycerolipids, or sphingolipids may be involved in the regulation of adiposity accumulation, affected by dietary exposures.

Optimization and application of high-throughput supported liquid extraction for simultaneous determination of carotenoids and fat-soluble vitamins in serum.

The demand for analysis of carotenoids (CAR) and fat-soluble vitamins (FSV) is continuously expanding, but currently used sample preparation methods either require complicated extraction procedure or large sample volume, let alone the reliability of the results. This study aimed to develop a fast, high-efficient, and high-throughput method based on supported liquid extraction (SLE) for the simultaneous extraction of FSV and CAR from human serum before using high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The optimization of SLE parameters was achieved through response surface methodology (RSM) based on the Box-Behnken design (BBD) and included serum-water-extraction solvent ratio and eluent volume. Under optimal conditions, the proposed method gives acceptable limits of detection (LOD) (0.005-0.3 µg/mL), good recovery (89.6-110.9%) as well as relative standard deviation (RSD) of less than 10.1% by consuming lower serum sample (100 µL) and less sample preparation time (2 min per sample). Compared with liquid-phase extraction (LLE), the SLE delivers rapid extraction with higher recovery, better reproducibility, and lower matrix effect for CAR and FSV analysis. The method has been successfully applied to quantify CAR and FSV levels in serum of healthy individuals and age-related macular degeneration (AMD) patients, demonstrating the feasibility of the proposed method for epidemiology and routine applications.

The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer.

Protein tyrosine phosphatase MEG2 (MEG2/PTPN9), a classic tyrosine-specific protein tyrosine phosphatase (PTP), is involved in the progression of liver, breast, and gastric cancers. However, the function and regulation of MEG2 in colorectal cancer (CRC) still remain unclear. In this study, we investigated the expression of MEG2 in CRC and found that MEG2 was downregulated in human CRC tissues compared to normal corresponding tissues. Moreover, in vivo and in vitro assays revealed that MEG2 plays a vital role in CRC cell proliferation, invasion, and apoptosis. In addition, mechanism analysis validated miR-21 as a direct regulator of MEG2, and miR-21 plays a critical role in promoting proliferation, invasion, and suppression of apoptosis in CRC by targeting MEG2. Taken together, this study demonstrates the significant role for miR-21 in regulating MEG2 in CRC and may represent a potential target for CRC therapy.

Predictor of sleep difficulty among community dwelling older populations in 2 African settings.

Sleep deprivation is a common phenomenon among older population and is commonly linked to behavioral, physiological, and psychosocial factors. Not much is known about sleep deprivation among older population in Africa. Therefore, in this study we aimed to investigate the basic sociodemographic and psychosocial predictors of self-reported sleep deprivation among older population.In this study we analyzed cross-sectional data on 1495 community dwelling men and women aged 50 years and above. Data were collected from the SAGE Well-Being of Older People Study conducted in South Africa and Uganda. Outcome variable was self-reported sleep difficulty last 30 days. Multivariable logistic regression models were used to identify the variables significantly associated with sleep difficulty.The prevalence of mild-moderate sleep difficulty was 32.6% (27.9, 37.6) and severe/extreme 23.0% (20.3, 26.0) respectively. Multivariable analysis revealed that sleep difficulty was associated with several behavioral, environment, and illness conditions. In South Africa, those who reported dissatisfaction with living condition had 1.592 [1.087, 2.787] times higher odds of reporting mild/moderate sleep difficulty. Poor subjective quality of life (QoL) was associated with higher odds of severe/extreme sleep difficulties (odds ratios [OR] = 4.590, 95% confidence interval [CI] = 2.641, 7.977 for South Africa, and OR = 4.461, 95% CI = 2.048 and 9.716 for Uganda). In Uganda, perceived depression was associated with higher odds of severe/extreme (OR = 2.452, 95% CI = 1.073, 5.602) sleep difficulties among men, and both mild/moderate (OR = 1.717; 95% CI = 1.011, 2.914) and severe/extreme sleep difficulties among women (OR = 2.504, 95% CI = 1.408, 4.453).More than half of the participants had sleep difficulty of certain degrees, emphasising an urgent need for intervention for sleep deprivation in the population. Interventions targeting to promote subjective health, quality of life, and living environment may prove beneficial for improving sleep health in this regard.

[Clinical values and optimal cut-off points of basic vital signs in early identification of critical hand, foot, and mouth disease].

OBJECTIVE: To study the clinical values of basic vital signs in early identification of critical hand-foot-mouth disease (HFMD). METHODS: The clinical data of 358 children with severe HFMD [212 cases in stage 2 (central nervous system involvement) and 146 cases in stage 3 (earlier stage of cardiopulmonary failure, critical type)] were reviewed. The diagnostic values of peak temperature and duration of fever, as well as the heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in different age groups, for critical HFMD (stage 3) were analyzed using the receiver operating characteristic (ROC) curve. RESULTS: HFMD might progress to critical type in case of HR≥148.5 beats/minutes, RR≥36.5 times/minutes, SBP≥95 mm Hg, and DBP≥59 mm Hg among children aged 0-1 year. HR≥142.5 times/minutes, RR≥31.5 times/mintes, SBP≥103 mm Hg, and DBP≥60.5 mm Hg in children aged 1-2 years had a certain diagnostic value for critical HFMD. HFMD might progress to critical type in case of HR≥139.5 times/minutes, RR≥29.5 times/minutes, and SBP≥103 mm Hg among children≥3 years of age. The sensitivity and specificity of every indicator were higher than 0.517 and 0.769, respectively. The area under the ROC curve (AUC) for peak temperature was 0.507 (P=0.816, compared with AUC=0.5). When the duration of fever was ≥5.5 days, the sensitivity and specificity were 0.589 and 0.571, respectively. CONCLUSIONS: HR, RR, and BP are good indicators to identify critical HFMD (stage 3) early. The optimal cut-off points conform to the age characteristics of children. DBP in children≥3 years of age, peak temperature, and duration of fever have a low value in early identification of critical HFMD.

The whole mitochondrial genome of the Cynomolgus macaque (Macaca fascicularis).

Macaca fascicularis, known as the long-tailed macaque, is widely distributed in southern of East Asia and Southeast Asia. It was one of the most commonly used non-human primates in biomedical research. Thus, to illustrate the maternal phylogenetic status of M. fascicularis in primates based on the whole mitochondrial DNA (mtDNA) genome and determine a reference sequence for future population genetic studies by taking mtDNA as molecular marker, in this study, the high quality whole mtDNA genome of M. fascicularis was amplified and sequenced. Our data showed that the whole mtDNA genome of M. fascicularis includes 16,571 base pairs (bps). Further phylogenetic analyses of M. fascicularis were performed by incorporating the 83 available whole mtDNA genomes belonging to 77 primate species with Tupaia belangeri as out-group. Our result supported that M. fascicularis belongs to Macaca. Cercopithecinae. Cercopithecidae. Anthropoidea. Primates, which has the closest genetic affinity with Macaca mulatta. In addition, the ancestral divergence between the tarsier and other primate species was supported with evidence from the whole mtDNA genomes.

Climatic warming increases winter wheat yield but reduces grain nitrogen concentration in east China.

Climatic warming is often predicted to reduce wheat yield and grain quality in China. However, direct evidence is still lacking. We conducted a three-year experiment with a Free Air Temperature Increase (FATI) facility to examine the responses of winter wheat growth and plant N accumulation to a moderate temperature increase of 1.5°C predicted to prevail by 2050 in East China. Three warming treatments (AW: all-day warming; DW: daytime warming; NW: nighttime warming) were applied for an entire growth period. Consistent warming effects on wheat plant were recorded across the experimental years. An increase of ca. 1.5°C in daily, daytime and nighttime mean temperatures shortened the length of pre-anthesis period averagely by 12.7, 8.3 and 10.7 d (P<0.05), respectively, but had no significant impact on the length of the post-anthesis period. Warming did not significantly alter the aboveground biomass production, but the grain yield was 16.3, 18.1 and 19.6% (P<0.05) higher in the AW, DW and NW plots than the non-warmed plot, respectively. Warming also significantly increased plant N uptake and total biomass N accumulation. However, warming significantly reduced grain N concentrations while increased N concentrations in the leaves and stems. Together, our results demonstrate differential impacts of warming on the depositions of grain starch and protein, highlighting the needs to further understand the mechanisms that underlie warming impacts on plant C and N metabolism in wheat.

PANC-1 pancreatic cancer cell growth inhibited by cucurmosin alone and in combination with an epidermal growth factor receptor-targeted drug.

OBJECTIVES: To investigate the inhibition of PANC-1 pancreatic cancer cell growth by cucurmosin (CUS) and its possible mechanism. METHODS: We observed the inhibition of PANC-1 cell growth by sulforhodamine B and colony-forming experiments in vitro and established nonobese diabetic/severe combined immunodeficiency mouse subcutaneous tumor models in vivo. We used Western blot to analyze protein levels related to apoptosis and epidermal growth factor receptor (EGFR) signaling pathways after drug intervention, whereas the messenger RNA expression of EGFR was analyzed by quantitative real-time polymerase chain reaction. RESULTS: Sulforhodamine B and colony-forming experiments indicated that CUS inhibited PANC-1 cell proliferation in a dose- and time-dependent manner. A stronger inhibitory effect was observed when CUS was combined with gefitinib. The subcutaneous tumor growth was also inhibited. Western blot showed that all the examined proteins decreased, except for 4E-BP1 and the active fragments of caspase 3 and caspase 9 increased. Epidermal growth factor receptor expression did not change significantly in quantitative real-time polymerase chain reaction. CONCLUSIONS: Cucurmosin can strongly inhibit the growth of PANC-1 cells in vitro and in vivo. Cucurmosin can down-regulate EGFR protein expression, but not at the messenger RNA level. Cucurmosin can also inhibit the ras/raf and phosphatidylinositol 3-kinase/Akt downstream signaling pathways and enhance the sensitivity of the EGFR-targeted drug gefitinib.

Cucurmosin induces the apoptosis of human pancreatic cancer CFPAC-1 cells by inactivating the PDGFR-ß signalling pathway.

BACKGROUND: Pancreatic cancer treatment is limited and effective drugs are needed. We investigated cucurmosin (CUS)-induced apoptosis in cystic fibrosis pancreatic adenocarcinoma cells (CFPAC-1) and a possible mechanism of action to evaluate the clinical application potential of this new Type I ribosome-inactivating protein. METHODS: We analyzed the growth inhibition and apoptosis of CFPAC-1 cells via methylthiazol tetrazolium assay and fluorescence-activated cell sorting. Western blot was used to analyze the protein levels of caspase 3, bcl-2, caspase 9, platelet-derived growth factor receptor (PDGFR)-ß, PI3K, Akt, p-Akt, the mammalian target of rapamycin (mTOR), p-mTOR, P70S6K-α, p-P70S6K-α, 4E-BP1, p-4E-BP1 and p-Bad after CUS intervention. The mRNA expression of PDGFR-ß was analyzed using reverse transcription polymerase chain reaction. RESULTS: CUS inhibited the proliferation of pancreatic cancer cells. The induction of apoptosis depended on the CUS dose and incubation time. The drug inhibited all of the examined proteins in the PI3K/Akt/mTOR signalling pathway and induced the active fragments of caspase 3 and caspase 9. CUS downregulated PDGFR-ß expression but no significant change was observed at the mRNA level. CONCLUSION: CUS strongly inhibits the growth of CFPAC-1 by inducing cell apoptosis. CUS downregulated the expression of PDGFR-ß at the protein level and induced the apoptosis of CFPAC-1 through the PI3K/Akt/mTOR signalling pathway.

Cucurmosin kills human pancreatic cancer SW-1990 cells in vitro and in vivo.

OBJECTIVE: To investigate the effect of cucurmosin (CUS) on proliferation inhibition in the human pancreatic cancer cell line SW-1990 in vitro and in vivo. METHODS: 1. MTT assay was used to analyse the proliferation inhibition of CUS in SW-1990 cells compared with gemcitabine (GEM) in vitro. 2. We established an NOD-SCID mice orthotopic transplantation model and estimated the proliferation inhibition effect of CUS in SW-1990 cells in vivo. 3. Western blot was used to determine the protein expressions of Caspase 3, Bcl-2, Caspase 9, PI3K, Akt, mTOR, P70S6k, and 4E-BP1 after CUS intervention. RESULTS: 1. CUS inhibited the proliferation of pancreatic cancer cells and induced apoptosis in CUS dose- and time-dependent manners. 2. NOD-SCID mice models were established successfully, and the tumour proliferation inhibition rates of these models increased compared with the control group. 3. CUS inhibited all of the examined proteins in the PI3K/Akt/mTOR signalling pathway and induced active fragments of Caspase 3 and Caspase 9. CONCLUSION: 1. CUS can inhibit the growth of SW-1990 cells in vitro and in vivo. 2. CUS can induce apoptosis in SW-1990 cells to inhibit cell growth.