Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulating TERT expression.

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT. Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation.

An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.

INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear. MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus. RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human. CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.

A prediction model for new-onset atrial fibrillation following coronary artery bypass graft surgery: A multicenter retrospective study.

Objective: Developing and assessing a risk prediction model of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG), and aims to provide a reference for the prediction and prevention. Design: A retrospective case-control study. Setting: Three major urban teaching and university hospitals and tertiary referral centers. Participants: consecutive patients undergoing CABG. Interventions: The study was retrospective and no interventions were administered to patients. Measurements and main results: In the study, the overall new-onset POAF prevalence was approximately 28%. A prediction model for POAF with nine significant indicators was developed, and identified new predictors of POAF: left ventricular end diastolic diameter (LVEDD), intraoperative defibrillation, and intraoperative temporary pacing lead implantation. The model had good discrimination in both the derivation and validation cohorts, with the area under the receiver operating characteristic curves (AUCs) of 0.621 (95% CI = 0.602-0.640) and 0.616 (95% CI = 0.579-0.651), respectively, and showed good calibration. Compared with CHA2DS2-VASc, HATCH score, and the prediction model of POAF after CABG developed based on a small sample of clinical data from a single center in China, the model in this study had better discrimination. Conclusion: We have developed and validated a new prediction model of POAF after CABG using multicenter data that can be used in the clinic for early identification of high-risk patients of POAF, and to help effectively prevent POAF in postoperative patients.

Comparison of in-hospital outcomes after coronary artery bypass graft surgery in elders and younger patients: a multicenter retrospective study.

OBJECTIVES: We aimed to identify in-hospital outcomes in young (≤ 65 years) and old (> 65 years) patients after coronary artery bypass grafting (CABG) by analyzing the effect of age on adverse events after on-pump or off-pump CABG. METHODS: Patients older than 65 years were defined as older patients and others were defined as younger patients. The qualitative data were compared by chi-square or Fisher's exact tests. The quantitative data were compared by the two-sample independent t-test or Mann-Whitney U test. Multifactor binary logistic regression was used to control for confounders and to investigate the effect of age on dichotomous outcome variables such as death. RESULTS: In the on-pump CABG population, the postoperative in-hospital mortality, the incidence of postoperative symptomatic cerebral infarction (POSCI) and postoperative atrial fibrillation (POAF) was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with postoperative in-hospital mortality (OR = 2.370, P value = 0.031), POSCI (OR = 5.033, P value = 0.013), and POAF (OR = 1.499, P value < 0.001). In the off-pump CABG population, the incidence of POAF was higher in older patients than in younger patients (P value < 0.05), and age > 65 years was associated with POAF (OR = 1.392, P value = 0.011). CONCLUSION: In-hospital outcomes after CABG are strongly influenced by age. In on-pump CABG, the risk of postoperative death, POSCI, and POAF was higher in older patients, and in off-pump CABG, the risk of POAF was higher in older patients.

Association of LDL to HDL ratio with new-onset atrial fibrillation after on-pump coronary artery bypass graft surgery.

OBJECTIVE: This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. METHODS: A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. RESULTS: In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529-0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775-0.886) and a specificity of 30.02% (95% CI = 0.257-0.346). CONCLUSION: Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.

Myo1b promotes tumor progression and angiogenesis by inhibiting autophagic degradation of HIF-1α in colorectal cancer.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Effect of CPB glucose levels on inflammatory response after pediatric cardiac surgery.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a common complication after cardiac surgery. There are no definite optimal glycemic threshold for pediatric patients receiving open-heart surgery with CPB. The study aimed to investigate the optimal cardiopulmonary bypass (CPB) glucose in patients undergoing cardiac surgery. METHODS: We enrolled children with congenital heart disease who underwent surgical repair between June 2012 and December 2020. We included only patients who underwent cardiac surgery with CPB. The primary outcome was severe SIRS. A two-piece-wise regression model was applied to examine threshold effect of CPB glucose on severe SIRS. RESULTS: A total of 7350 patients were enrolled in the present study, of whom 3895 (52.99%) are female. After potential confounders were adjusted, non-linear relationship was detected between CPB glucose and severe SIRS, whose turning point was 8.1. With CPB glucose < 8.1 mmol/L, the estimated dose-response curve was consistent with a horizontal line. However, the prevalence of severe SIRS increased with increasing glucose up to the turning point (Glucose > 8.1 mmol/L); the odds ratio (OR) of the Glucose was 1.35 (95% CI 1.21, 1.50). CONCLUSIONS: The present study indicates the association of CPB glucose with inflammatory response after pediatric cardiac surgery. The patients might have the best outcomes with the optimal CPB glucose no more than 8.1 mmol/L.

Enhanced performance of polyimide hybrid membranes for benzene separation by incorporating three-dimensional silver-graphene oxide.

Graphene oxide-Ag nanoparticle composites were prepared through impregnation reduction using different reactants. Transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy analyses were performed to characterize differences in the morphologies of three different Ag-GO composites. Scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry analyses were also applied to evaluate the morphology and thermal stability of the hybrid membranes. Swelling-sorption and pervaporation experiments of benzene and cyclohexane were conducted to evaluate the separation performance of hybrid membranes containing different Ag-GO composites. Results demonstrated that small Ag nanoparticles generated through impregnation reduction using Ag(NH3)2(+) and PEG were homogeneously distributed in the hybrid membranes because of moderate reduction rate. The polymide (PI) hybrid membrane exhibited high separation performance. Increase in Ag content in the Ag-GO samples led to the formation of Ag particles on the GO surface; these particles enhanced the separation performance of the hybrid membranes. When Ag-GO samples with 15 mass percent added, the hybrid membrane showed the highest separation performance and its maximum separation factor in the pervaporation experiments reached 35. It is more than three times higher than that of the GO/PI hybrid membrane. Moreover, large Ag particles were formed and aggregated during the preparation and polymerization of Ag-GO samples with high Ag contents; these particles reduced the separation performance of the hybrid membranes.