An anoikis-related lncRNA signature may predict the prognosis, immune infiltration, and drug sensitivity in esophageal cancer.

Background: Esophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. Methods: Transcriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. Results: We identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. Conclusion: This study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

Enhanced piezocatalytic and piezo-photocatalytic dye degradation via S-scheme mechanism with photodeposited nickel oxide nanoparticles on PbBiO2Br nanosheets.

The fabrication of an S-scheme heterojunction demonstrates as an efficient strategy for achieving efficient charge separation and enhancing catalytic activity of piezocatalysts. In this study, a new S-scheme heterojunction was fabricated on the PbBiO2Br surface through the photo-deposition of NiO nanoparticles. It was then employed in the piezoelectric catalytic degradation of Rhodamine B (RhB). The results demonstrate that the NiO/PbBiO2Br composite exhibits efficient performance in piezocatalytic RhB degradation. The optimal sample is the NiO/PbBiO2Br synthesized after 2 h of irradiation, achieving a RhB degradation rate of 3.11 h-1, which is 12.4 times higher than that of pure PbBiO2Br. Simultaneous exposure to visible light and ultrasound further increases in the RhB degradation rate, reaching 4.60 h-1, highlighting the synergistic effect of light and piezoelectricity in the NiO/PbBiO2Br composite. A comprehensive exploration of the charge migration mechanism at the NiO/PbBiO2Br heterojunction was undertaken through electrochemical analyses, theoretical calculations, and in-situ X-ray photoelectron spectroscopy analysis. The outcomes reveal that p-type semiconductor NiO and n-type semiconductor PbBiO2Br possess matching band structures, establishing an S-scheme heterojunction structure at their interface. Under the combined effects of band bending, interface electric fields, and Coulomb attraction, electrons and holes migrate and accumulate on the conduction band of PbBiO2Br and valence band of NiO, respectively, thereby achieving effective spatial separation of charge carriers. The catalyst's synergistic photo-piezoelectric catalysis effect can be ascribed to its role in promoting the generation and separation of charge carriers under both light irradiation and the piezoelectric field. The results of this investigation offer valuable insights into the development and production of catalytic materials that exhibit outstanding performance through the synergy of piezocatalysis and photocatalysis.

Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

OBJECTIVE: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations. METHODS: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings. RESULTS: Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences. CONCLUSION: Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points • This study determines the causally protective effect of coffee intake on gout. • We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. • Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.

A Treg-related riskscore model may improve the prognosis evaluation of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) poses a significant health challenge. This study aims to investigate the prognostic value of a regulatory T cell (Treg)-related gene signature in CRC. METHODS: We extracted the gene expression and clinical data on CRC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The gene module related to Treg was identified by weighted gene co-expression network analysis (WGCNA). The genes in the significant module were filtered by univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. A riskscore model was established in terms of the key Treg-related genes. The reliability of this riskscore model was validated using the external GEO dataset. The association of riskscore with clinical features, mutation patterns and signaling pathways was explored. RESULTS: Genes in the blue module showed the strongest association with Tregs. After a series of filtering cycles, seven Treg-related key genes, GDE1, GSR, HSPB1, AOC2, TBX19, TAMM41 and TIGD6, were selected to construct a riskscore model. This model performed well in evaluating the patients' survival in TCGA cohort, and was further affirmed by the GSE17536 validation cohort. For precise evaluation of the patients' survival, we established a nomogram in light of riskscore and clinical factors. Patients in different risk groups had distinct clinical features, mutation patterns and signaling pathway activities. The expression of five key genes was significantly associated with Treg infiltration in the CRC samples. CONCLUSION: We established a useful riskscore model in light of seven Treg-related genes. This model may contribute to the prognosis evaluation, direct tailored treatment, and hopefully improve clinical outcomes of the CRC patients.

ß-hydroxybutyrate administered at reperfusion reduces infarct size and preserves cardiac function by improving mitochondrial function through autophagy in male mice.

Ischemia/reperfusion (I/R) injury after revascularization contributes ∼50% of infarct size and causes heart failure, for which no established clinical treatment exists. ß-hydroxybutyrate (ß-OHB), which serves as both an energy source and a signaling molecule, has recently been reported to be cardioprotective when administered immediately before I/R and continuously after reperfusion. This study aims to determine whether administering ß-OHB at the time of reperfusion with a single dose can alleviate I/R injury and, if so, to define the mechanisms involved. We found plasma ß-OHB levels were elevated during ischemia in STEMI patients, albeit not to myocardial protection level, and decreased after revascularization. In mice, compared with normal saline, ß-OHB administrated at reperfusion reduced infarct size (by 50%) and preserved cardiac function, as well as activated autophagy and preserved mtDNA levels in the border zone. Our treatment with one dose ß-OHB reached a level achievable with fasting and strenuous physical activity. In neonatal rat ventricular myocytes (NRVMs) subjected to I/R, ß-OHB at physiologic level reduced cell death, increased autophagy, preserved mitochondrial mass, function, and membrane potential, in addition to attenuating reactive oxygen species (ROS) levels. ATG7 knockdown/knockout abolished the protective effects of ß-OHB observed both in vitro and in vivo. Mechanistically, ß-OHB's cardioprotective effects were associated with inhibition of mTOR signaling. In conclusion, ß-OHB, when administered at reperfusion, reduces infarct size and maintains mitochondrial homeostasis by increasing autophagic flux (potentially through mTOR inhibition). Since ß-OHB has been safely tested in heart failure patients, it may be a viable therapeutic to reduce infarct size in STEMI patients.

Riskscore Model Based on Oxidative Stress-Related Genes May Facilitate the Prognosis Evaluation for Patients With Colon Cancer.

INTRODUCTION: This study aims to identify the oxidative stress-related genes (OSRGs) with prognostic value and develop a riskscore model for prognosis evaluation in colon cancer. METHODS: The transcriptome data and corresponding clinical information about colon cancer were extracted from The Cancer Genome Atlas database. Differentially expressed OSRGs and transcription factors (TFs) were identified between the normal and tumor samples. A riskscore model was established with OSRGs filtered from Cox regression analysis. This riskscore model was appraised by Kaplan-Meier plot, receiver operating characteristic curve, and Cox regression analysis. The clinical relevance of riskscore and its association with immune cell infiltration were also evaluated. RESULTS: A total of 307 differentially expressed OSRGs and 64 differential TFs were identified. A TF-OSRG regulatory network was constructed in Cytoscape software. A riskscore model was established based on 17 OSRGs with independent prognostic value. This riskscore model could separate the patients into low-risk and high-risk groups. It also had good predictive ability, with an area under the curve = 0.8. In multivariate Cox regression analysis, age, T stage, and riskscore were identified as independent risk factors in colon cancer. Riskscore was significantly correlated with T stage, N stage, and immune cell infiltration. DISCUSSION: We established a useful riskscore model with 17 OSRGs for prognosticating the overall survival in patients with colon cancer. This study provides a new insight into the clinical utility of OSRG-based riskscore model, which will hopefully facilitate the prognosis evaluation of patients with colon cancer.

Mitigation of atrazine-induced oxidative stress on soybean seedlings after co-inoculation with atrazine-degrading bacterium Arthrobacter sp. DNS10 and inorganic phosphorus-solubilizing bacterium Enterobacter sp. P1.

Atrazine toxicity is one of the limiting factors inhibiting sensitive plant growth. Previous studies showed that atrazine-degrading bacteria could alleviate atrazine toxicity. However, there is limited information on how atrazine-degrading bacteria and plant growth-promote bacteria alleviate atrazine toxicity in soybeans. Therefore, the current study aimed to explore the atrazine removal, phosphorus utilization, and the oxidative stress alleviation of atrazine-degrading bacterium Arthrobacter sp. DNS10 and/or inorganic phosphorus-solubilizing bacterium Enterobacter sp. P1 in the reduction of atrazine toxicity in soybean. The results showed that atrazine exposure to soybean seedlings led to significant inhibition in growth, atrazine removal, and phosphorus utilization. However, the co-inoculatied strains significantly increased seedlings biomass, chlorophyll a/b contents, and total phosphorus in leaves accompanied by great reduction of the atrazine-induced antioxidant enzymes activities and malonaldehyde (MDA) contents, as well as atrazine contents in soil and soybeans under atrazine stress. Furthermore, transcriptome analysis highlighted that co-inoculated strains increased the expression levels of genes related to photosynthetic-antenna proteins, carbohydrate metabolism, and fatty acid degradation in leaves. All the results suggest that the co-inoculation mitigates atrazine-induced oxidative stress on soybean by accelerating atrazine removal from soil and phosphorus accumulation in leaves, enhancing the chlorophyll contents, and regulating plant transcriptome. It may be suggested that co-inoculation of atrazine-degrading bacteria and inorganic phosphorus-solubilizing bacteria can be used as a potential method to alleviate atrazine toxicity to the sensitive crops.

Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation.

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment of restenosis by the paracrine function of extracellular vesicles (EVs). However, the risk of tumorigenicity and poor cell survival limits its clinical applications. In this study, we for the first time applied a highly efficient and robust three-dimensional (3D) protocol for hiPSC differentiation into endothelial cells (ECs) with subsequent isolation of EVs from the derived hiPSC-EC (ECs differentiated from hiPSCs), and validated their therapeutic effect in intimal hyperplasia (IH) models. We found that intravenously (iv) injected EVs could accumulate on the carotid artery endothelium and significantly alleviate the intimal thickening induced by the carotid artery ligation. To elucidate the mechanism of this endothelial protection, we performed miRNA expression profiling and found out that among the most conserved endothelial miRNAs, miR-126 was the most abundant in hiPSC-EC-produced EVs (hiPSC-EC-EV). MiR-126 depletion from hiPSC-EC-EV can hinder its protective effect on human umbilical vein endothelial cells (HUVECs) in an inflammatory process. A variety of functional in vitro studies revealed that miR-126 was able to prevent endothelial apoptosis after inflammatory stimulation, as well as promote EC migration and tube formation through autophagy upregulation. The latter was supported by in vivo studies demonstrating that treatment with hiPSC-EC-EV can upregulate autophagy in mouse carotid artery ECs, thereby preventing IH and modulating vascular homeostasis via remodeling of the vascular intima. Our findings suggest a regulatory mechanism for the therapeutic effect on arterial restenosis by autophagy regulation, and provide a potential strategy for clinical treatment of the disease.

Growth, biofilm formation and atrazine degrading gene (trzN) expression of Arthrobacter sp. DNS10 cultured with montmorillonite, kaolinite and goethite.

The viable and degradation potential of the strains which adhered to soil minerals are essential for eliminating organic pollutants from soil. Herein, the interaction (growth, biofilm formation and survive) of Arthrobacter sp. DNS10, an atrazine degrading strain, with three kinds of typical soil minerals, such as montmorillonite, kaolinite and goethite, as well as the atrazine degradation gene (trzN) expression of the strain in the minerals system were studied. The results showed that montmorillonite had significant promotion effect on the growth of strain DNS10, followed by kaolinite, but goethite significantly inhibited the growth of strain DNS10. In contrast, goethite notably promoted the biofilm formation and there was less biofilm detected in montmorillonite containing system. The percentage of the survival bacteria in the biofilm that formed on montmorillonite, kaolinite and goethite was 53.8%, 40.8% and 28.2%. In addition, there were more reactive oxygen species (ROS) were detected in the cells that exposed to goethite than those of the cells exposed to kaolinite and montmorillonite. These results suggest that the electrostatic repulsion between kaolinite/montmorillonite and strain DNS10 prevents them from contacting each other and facilitates bacterial growth by allowing the strain to obtain more nutrients. Oppositely, the needle-like morphology of goethite might damage the strain DNS10 cell when they were combined by electrostatic attraction, and the goethite induced ROS also aggravate the cytotoxicity of goethite on strain DNS10. In addition, the relative transcription of trzN in the cells contacted with montmorillonite, kaolinite and goethite was 0.94-, 0.27- and 0.20- fold of the no mineral exposure treatment. Briefly, this research suggests that the minerals with different structure and/or physicochemical characteristics might cause various trend for the biofilm formation and degradation potential of the bacteria.

Activation of Autophagic Flux Maintains Mitochondrial Homeostasis during Cardiac Ischemia/Reperfusion Injury.

Reperfusion injury after extended ischemia accounts for approximately 50% of myocardial infarct size, and there is no standard therapy. HDAC inhibition reduces infarct size and enhances cardiomyocyte autophagy and PGC1α-mediated mitochondrial biogenesis when administered at the time of reperfusion. Furthermore, a specific autophagy-inducing peptide, Tat-Beclin 1 (TB), reduces infarct size when administered at the time of reperfusion. However, since SAHA affects multiple pathways in addition to inducing autophagy, whether autophagic flux induced by TB maintains mitochondrial homeostasis during ischemia/reperfusion (I/R) injury is unknown. We tested whether the augmentation of autophagic flux by TB has cardioprotection by preserving mitochondrial homeostasis both in vitro and in vivo. Wild-type mice were randomized into two groups: Tat-Scrambled (TS) peptide as the control and TB as the experimental group. Mice were subjected to I/R surgery (45 min coronary ligation, 24 h reperfusion). Autophagic flux, mitochondrial DNA (mtDNA), mitochondrial morphology, and mitochondrial dynamic genes were assayed. Cultured neonatal rat ventricular myocytes (NRVMs) were treated with a simulated I/R injury to verify cardiomyocyte specificity. The essential autophagy gene, ATG7, conditional cardiomyocyte-specific knockout (ATG7 cKO) mice, and isolated adult mouse ventricular myocytes (AMVMs) were used to evaluate the dependency of autophagy in adult cardiomyocytes. In NRVMs subjected to I/R, TB increased autophagic flux, mtDNA content, mitochondrial function, reduced reactive oxygen species (ROS), and mtDNA damage. Similarly, in the infarct border zone of the mouse heart, TB induced autophagy, increased mitochondrial size and mtDNA content, and promoted the expression of PGC1α and mitochondrial dynamic genes. Conversely, loss of ATG7 in AMVMs and in the myocardium of ATG7 cKO mice abolished the beneficial effects of TB on mitochondrial homeostasis. Thus, autophagic flux is a sufficient and essential process to mitigate myocardial reperfusion injury by maintaining mitochondrial homeostasis and partly by inducing PGC1α-mediated mitochondrial biogenesis.

The Incidence-Based Mortality and Survival Trends in Patients with Gastric Signet Ring Cell Carcinoma.

Materials and Methods: The patients from the Surveillance, Epidemiology, and End Results (SEER) database were recruited to explore the incidence-based mortality and survival trends from 2000 to 2017. We further analyzed the differences in mortality and survival trends in these patients by sex and stage. We also used joinpoint software to evaluate the trends in annual percentage change (APC) for statistical significance. Results: 14916 patients were collected, including 7801 (52.3%) male and 7115 (47.7%) female. We identified a single joinpoint at 2002. The overall incidence-based mortality of gastric SRC declined in America after 2002 (APC = -1.21, P < 0.05). In stratified analysis by sex and stage, the incidence-based mortality rate was higher in males than females. After 2002, the mortality rate decreased significantly in male (APC = -1.68, P < 0.05) and M0-stage patients (APC = -1.75, P < 0.05). In survival trend analysis, the 2-year relative survival improved in M0-stage gastric SRC, especially for males (APC = 1.14, P < 0.05). As for M1-stage patients, the 2-year relative survival significantly elevated in both male (APC = 3.87, P < 0.05) and female (APC = 5.63, P < 0.05) patients. Conclusions: The incidence-based mortality of gastric SRC has declined, and survival has improved in America over time. These optimistic trends may be attributed to cancer screening implementation and advances in novel treatments in the past decades.

The Clinicopathological Features and Overall Survival of Patients With Gastric Neuroendocrine Carcinoma.

OBJECTIVES: Gastric neuroendocrine carcinoma (GNEC) is a class of rare histological subtypes in gastric cancer (GC). This retrospective case-control study aimed to explore the clinicopathological features and overall survival (OS) of patients with GNEC. METHODS: A large population of GNEC and intestinal-type GC (IGC) patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The 1:1 propensity score matching (PSM) analysis was initiated to adjust the confounders between GNEC and IGC cohorts. Kaplan-Meier (KM) plots with log-rank tests were used to compare the survival differences in GNEC versus IGC. Additionally, Cox proportional hazard regression models were adopted to characterize the prognostic factors relevant to OS of the GNEC patients. RESULTS: An entity of 4596 patients were collected, including 3943 (85.8%) IGC patients and 653 (14.2%) GNEC patients. The PSM analysis well-balanced all confounders in GNEC versus IGC (all P > .05). The KM plots showed that GNEC had significantly superior OS to IGC both before and after PSM analysis. Before PSM, the median OS was 52 (33.6-70.4) months in GNEC versus 32 (29.3-34.7) months in IGC (P = .0015). After PSM, the median OS was 26 (18.3-33.7) months in GNEC versus 21 (17.7-24.3) months in IGC (P = .0039). Stratified analysis indicated that GNEC had superior survivals to IGC in early stage patients and those who received surgery. In Cox regression analysis, age ≥ 60, tumor size > 50 mm, stage II-IV, T2, and N3 were independent risk factors for the GNEC patients (hazard ratio [HR]>1, P < .05). By contrast, year 2010 to 2015, female, and surgery were independent protective factors for these patients (HR < 1, P < .05). CONCLUSIONS: GNEC has unique clinicopathological features quite different from IGC and may have a superior survival to IGC in early stage patients. The prognostic factors identified here may assist the clinicians to more individually treat these patients.

Primary tumor resection benefited the survival of patients with distant metastatic gastric cancer.

BACKGROUND: The role of surgery in the treatment of patients with distant metastatic (M1) gastric cancer (GC) remains controversial currently. This study aimed to clarify the impact of primary tumor resection (PTR) on the survival of such patients. MATERIALS AND METHODS: The surveillance, epidemiology, and end results database was adopted to extract eligible patients. We designed a retrospective case-control study. The patients were divided into two groups according to whether they received PTR. The 1:1 propensity score matching (PSM) analysis was performed to balance the confounding factors between no-surgery and surgery groups. The categorical variables were described with Chi-square tests. Cancer-specific survival (CSS) and overall survival (OS) were evaluated by Kaplan-Meier method with log-rank test. Cox proportional hazard models were utilized to identify prognostic factors of CSS. RESULTS: A total of 1716 patients were included, including 1108 (64.6%) patients without surgery and 608 (35.4%) patients with surgery. After PSM, most confounders were well balanced between the two comparison groups. Survival analysis in matched cohorts indicated that surgery exerted significant survival advantages in both CSS and OS curves. The median CSS was 11.0 (9.8-12.2) months in the surgery group versus 9.0 (8.0-10.0) months in the no-surgery group (P < 0.001). Multivariable Cox regression analysis identified surgery as an independent prognostic factor for favorable prognosis (hazard ratio: 0.689, 95% confidence interval: 0.538-0.881, P = 0.003). CONCLUSION: Surgery showed significant survival benefits for the patients with M1 stage GC. Our study has provided additional evidence to support PTR for these patients.

Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction.

BACKGROUND: Human induced pluripotent stem cells with normal (wild-type) or upregulated (overexpressed) levels of CCND2 (cyclin D2) expression were differentiated into cardiomyocytes (CCND2WTCMs or CCND2OECMs, respectively) and injected into infarcted pig hearts. METHODS: Acute myocardial infarction was induced by a 60-minute occlusion of the left anterior descending coronary artery. Immediately after reperfusion, CCND2WTCMs or CCND2OECMs (3×107 cells each) or an equivalent volume of the delivery vehicle was injected around the infarct border zone area. RESULTS: The number of the engrafted CCND2OECMs exceeded that of the engrafted CCND2WTCMs from 6- to 8-fold, rising from 1 week to 4 weeks after implantation. In contrast to the treatment with the CCND2WTCMs or the delivery vehicle, the administration of CCND2OECM was associated with significantly improved left ventricular function, as revealed by magnetic resonance imaging. This correlated with reduction of infarct size, fibrosis, ventricular hypertrophy, and cardiomyocyte apoptosis, and increase of vascular density and arterial density, as per histologic analysis of the treated hearts. Expression of cell proliferation markers (eg, Ki67, phosphorylated histone 3, and Aurora B kinase) was also significantly upregulated in the recipient cardiomyocytes from the CCND2OECM-treated than from the CCND2WTCM-treated pigs. The cell proliferation rate and the hypoxia tolerance measured in cultured human induced pluripotent stem cell cardiomyocytes were significantly greater after treatment with exosomes isolated from the CCND2OECMs (CCND2OEExos) than from the CCND2WTCMs (CCND2WTExos). As demonstrated by our study, CCND2OEExos can also promote the proliferation activity of postnatal rat and adult mouse cardiomyocytes. A bulk miRNA sequencing analysis of CCND2OEExos versus CCND2WTExos identified 206 and 91 miRNAs that were significantly upregulated and downregulated, respectively. Gene ontology enrichment analysis identified significant differences in the expression profiles of miRNAs from various functional categories and pathways, including miRNAs implicated in cell-cycle checkpoints (G2/M and G1/S transitions), or the mechanism of cytokinesis. CONCLUSIONS: We demonstrated that enhanced potency of CCND2OECMs promoted myocyte proliferation in both grafts and recipient tissue in a large mammal acute myocardial infarction model. These results suggest that CCND2OECMs transplantation may be a potential therapeutic strategy for the repair of infarcted hearts.

Beta-Hydroxybutyrate, Friend or Foe for Stressed Hearts.

One of the characteristics of the failing human heart is a significant alteration in its energy metabolism. Recently, a ketone body, ß-hydroxybutyrate (ß-OHB) has been implicated in the failing heart's energy metabolism as an alternative "fuel source." Utilization of ß-OHB in the failing heart increases, and this serves as a "fuel switch" that has been demonstrated to become an adaptive response to stress during the heart failure progression in both diabetic and non-diabetic patients. In addition to serving as an alternative "fuel," ß-OHB represents a signaling molecule that acts as an endogenous histone deacetylase (HDAC) inhibitor. It can increase histone acetylation or lysine acetylation of other signaling molecules. ß-OHB has been shown to decrease the production of reactive oxygen species and activate autophagy. Moreover, ß-OHB works as an NLR family pyrin domain-containing protein 3 (Nlrp3) inflammasome inhibitor and reduces Nlrp3-mediated inflammatory responses. It has also been reported that ß-OHB plays a role in transcriptional or post-translational regulations of various genes' expression. Increasing ß-OHB levels prior to ischemia/reperfusion injury results in a reduced infarct size in rodents, likely due to the signaling function of ß-OHB in addition to its role in providing energy. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to exert strong beneficial effects on the cardiovascular system. They are also capable of increasing the production of ß-OHB, which may partially explain their clinical efficacy. Despite all of the beneficial effects of ß-OHB, some studies have shown detrimental effects of long-term exposure to ß-OHB. Furthermore, not all means of increasing ß-OHB levels in the heart are equally effective in treating heart failure. The best timing and therapeutic strategies for the delivery of ß-OHB to treat heart disease are unknown and yet to be determined. In this review, we focus on the crucial role of ketone bodies, particularly ß-OHB, as both an energy source and a signaling molecule in the stressed heart and the overall therapeutic potential of this compound for cardiovascular diseases.

Brain Metastasis in Patients with Small Cell Lung Cancer.

PURPOSE: To characterize the risk factors for brain metastasis (BM) at presentation and analyze the prognostic factors for patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients were recruited from the SEER database between 2010 and 2016. They were divided into two groups according to BM status. The incidence trends of SCLC and its BM were analyzed by joinpoint software. The risk factors for BM in SCLC were identified by binary logistic regression models. The prognostic factors for SCLC patients with BM were identified by Cox proportional hazard models. RESULTS: The incidence of SCLC and its BM significantly decreased after 2010. Totally 11,093 patients were collected, including 1717 (15.5%) patients with BM and 9376 (84.5%) patients without BM. In multivariate logistic regression analysis, age, male and higher T stage were independent risk factors for BM in SCLC patients at presentation. SCLC patients with BM showed inferior survival to those without BM. In multivariate Cox regression analysis, increasing age, large tumor size, and higher N stage were risk factors for poor prognosis, while other race, surgery, adjuvant radiotherapy, and chemotherapy were protective factors for SCLC patients with BM. A nomogram was developed for prognosis evaluation of such patients. CONCLUSION: Age, male and higher T stage were risk factors for BM in SCLC patients at presentation. Increasing age, large tumor size, and advanced N stage may predict poor survival for SCLC patients with BM. Multidisciplinary therapies may provide clinical benefits. This study will help identify patients with higher BM risk and hopefully improve their clinical outcome.

Preoperative Radiotherapy Is Associated With Significant Survival Benefits for Patients With Gastric Signet Ring Cell Carcinoma: A SEER-Based Approach.

OBJECTIVE: To explore the clinical and pathological features of gastric signet ring cell carcinoma, and evaluate the survival impact of preoperative radiotherapy on these patients. METHODS: The Surveillance, Epidemiology, and End Results database was used to extract eligible patients from 2004 to 2015. The patients were divided into those with and without preoperative radiotherapy. The categorical variables were described by chi-square tests. The patients' survival was compared between the 2 groups by Kaplan-Meier method with log-rank tests. Cox proportional hazard model was adopted to identify prognostic factors of cancer-specific survival. RESULTS: Totally 4771 patients were recruited, of whom 218(4.6%) patients received preoperative radiotherapy, while 4553(95.4%) patients didn't receive this treatment. Survival analysis of the entire cohort demonstrated that preoperative radiotherapy improved both cancer-specific survival and overall survival (p < 0.001) of the patients. Cox proportional hazard models identified age >60, tumor size >50 mm, TNM stage II-IV as independent risk factors for poor prognosis (HR > 1, p < 0.05). Notably, preoperative radiotherapy was identified as an independent protective factor for favorable prognosis (HR < 1, p < 0.05). Subgroup survival analysis showed that preoperative radiotherapy exerted significant survival benefits for the stages III and IV patients. CONCLUSIONS: In this population-based study, preoperative radiotherapy is associated with significant survival benefits for the patients with advanced gastric signet ring cell carcinoma. Hence preoperative radiotherapy is feasible for these patients.

Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages I and II gastric cancer.

BACKGROUND: Primary gastric adenosquamous carcinoma (ASC) is an exceedingly rare histological subtype. Gastric signet ring cell carcinoma (SRC) is a unique subtype with distinct tumor biology and clinical features. The prognosis of gastric ASC vs SRC has not been well established to date. We hypothesized that further knowledge about these distinct cancers would improve the clinical management of such patients. AIM: To investigate the clinicopathological characteristics and prognosis of gastric ASC vs SRC. METHODS: A cohort of gastric cancer patients was retrospectively collected from the Surveillance, epidemiology, and end results program database. The 1:4 propensity score matching was performed among this cohort. The clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive statistics. Kaplan-Meier method was utilized to calculate the median survival of the two groups of patients. Cox proportional hazard regression models were used to identify prognostic factors. RESULTS: Totally 6063 patients with gastric ASC or SRC were identified. A cohort of 465 patients was recruited to the matched population, including 370 patients with SRC and 95 patients with ASC. Gastric ASC showed an inferior prognosis to SRC after propensity score matching. In the post-matching cohort, the median cancer specific survival was 13.0 (9.7-16.3) mo in the ASC group vs 20.0 (15.7-24.3) mo in the SRC group, and the median overall survival had a similar trend (P < 0.05). ASC and higher tumor-node-metastasis stage were independently associated with a poor survival, while radiotherapy and surgery were independent protective factors for improved prognosis. Subgroup survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II patients. CONCLUSION: ASC may have an inferior prognosis to SRC in patients with stages I and II gastric cancer. Our study supports radiotherapy and surgery for the future management of this clinically rare entity.

Adjuvant radiotherapy may have significant survival benefits for gastric cancer patients with 1-29 lymph nodes retrieved.

BACKGROUND: The role of adjuvant radiotherapy (RT) in gastric cancer (GC) patients has not been well-established. This study initiated a retrospective case-control study to explore the survival impact of adjuvant RT on these patients. METHODS: All patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was assigned into patients without adjuvant RT versus those with adjuvant RT. Descriptive chi-square test was adopted to compare categorical variates between the 2 groups. Kaplan-Meier (KM) method was adopted to estimate the patients' cancer-specific survival (CSS) and overall survival (OS). Cox proportional hazard models were utilized to characterize the prognostic factors of their CSS. RESULTS: Totally 7,194 patients were recruited in this study, 3,326 (46.2%) patients didn't have RT and 3,868 (53.8%) patients had adjuvant RT. Survival analysis of the entire population showed that adjuvant RT had remarkable survival benefits for the GC patients. The median CSS was 47.0 (42.0-52.0) months in RT group versus 32.0 (29.7-34.3) months in no RT group (P<0.001). Age >60, histologic type 8490, tumor size >50 mm, higher stage TNM, and surgery type 40/50 were independent risk factors for poor prognosis. Comparatively, adjuvant RT and LN examined >0 were independent factors for improving prognosis. Subgroup analysis demonstrated that adjuvant RT had significant survival benefits for patients with 1-14 and 15-29 lymph nodes (LNs) retrieved. CONCLUSIONS: Adjuvant radiotherapy may have significant survival benefits for GC patients with 1-29 LNs retrieved. Our study upholds adjuvant RT for this subset of patients.

Risk factors for distant metastasis of patients with primary triple-negative breast cancer.

Objective: Triple-negative breast cancer (TNBC) involves higher rates of recurrence and distant metastasis. The present study sought to characterize the risk factors for distant metastasis of TNBC.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was exploited to enroll patients diagnosed with TNBC from 2010 to 2015. The eligible patients were dichotomized into locoregional and distant metastasis at the time of diagnosis. Patients' demographics and tumor features, and treatment were evaluated to identify the risk factors for distant metastasis of primary TNBC. The categorical variables were examined by chi-square tests. Univariate and multivariate logistic regression analyses were used to determine the risk factors for distant metastasis. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated by Kaplan-Meier plots with log-rank tests.Results: We collected 26863 patients with primary TNBC, 1330 (5.0%) of them presented with distant metastasis. In the univariate analysis, all the variables indicated statistical significance. The significant variables were subsequently enlisted into the multivariate logistic regression analysis. Age > 50, higher clinical stage T and N, and tumor size > 5 cm were independent risk factors for distant metastasis of primary TNBC. Moreover, higher clinical stage T and stage N were independent risk factors for bone metastasis of the patients. TNBC patients with either bone or visceral metastasis have poor survival, with brain metastasis worst of all, though the OS difference was not statistically significant.Conclusions: TNBC patients with larger age, higher clinical stage, larger tumor size were more predisposed to have distant metastasis. Great attention should be paid to the prognosis of these patients with distant metastasis.