Promotion of Raf-1/ASK1 complex formation by corylin inhibits cell apoptosis in myocardial ischemia/reperfusion injury.

Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.

Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

Transcutaneous electrical acupoint stimulation for prevention of postoperative urinary retention: A systematic review.

Introduction: Transcutaneous electrical acupoint stimulation (TEAS) has been proposed for postoperative urinary retention (POUR). This meta-analysis evaluated the effect of TEAS in preventing POUR. Methods: Databases were searched until February 6, 2023. Randomized controlled trials (RCTs) about TEAS for preventing POUR were included. The primary concern was the incidence of POUR, with post-void residual urine volume as a secondary outcome. Results: Fourteen studies with 2865 participants were identified. TEAS reduced the incidence of POUR (RR = 0.44, 95%CI = 0.33 to 0.58, P < 0.00001) and decreased the post-void residual urine volume (MD = -75.41 mL, 95%CI = -118.76 to -32.06, P = 0.0007). The preventive effect on POUR was found in patients receiving anorectal, gynecologic, orthopedic and biliary surgery, but not urinary surgery. Dilatational- and continuous-wave TEAS had a great outcome in preventing POUR. Intraoperative TEAS, preoperative and intraoperative TEAS, and postoperative TEAS were beneficial, and TEAS was more beneficial when compared with sham TEAS and blank control. It is nevertheless difficult to rule out publication bias. Conclusions: TEAS could prevent POUR. Due to insufficient evidence, multicenter, large-sample and high-quality RCTs should be conducted. (Registration:INPLASY202320095).

Characteristics and risk factors for colorectal polyps among children in an urban area of Wenzhou, China: a retrospective case control study.

BACKGROUND: Scarce evidence exists on pediatric colorectal polyp risk factors. This study explored the clinical manifestations, morphological and pathological characteristics of, and risk factors for pediatric colorectal polyps. METHODS: This retrospective case-control study included children who received colonoscopy, divided into a colorectal polyp group and a normal control group based on colonoscopy results. The risk factors for colorectal polyps in children were analyzed through logistic regression analysis. RESULTS: The mean age of children with polyps was 6.77 ± 3.44 years. Polyps were detected predominantly in males (72.9%); hematochezia was the primary clinical manifestation (80.25%). Most polyps were juvenile (88.9%) and solitary (87.7%); 50.6% were located in the rectosigmoid area. Univariate analysis showed that gender (P = 0.037), age (P < 0.001), family aggregation (P < 0.001), specific immunoglobulin E (sIgE) (P < 0.001), platelet count (P = 0.001), aspartate aminotransferase (AST) (P = 0.016), meat intake (P = 0.010), and vegetable intake (P < 0.001) were significantly associated with colorectal polyps. Age ≤ 6 years (3-6 years: OR: 26.601, 95% CI: 3.761-160.910; < 3 years: OR: 22.678, 95% CI: 1.873-274.535), positive family aggregation (OR: 3.540, 95% CI: 1.177-10.643), positive sIgE (OR:2.263, 95% CI: 1.076-4.761), and higher meat intake (OR:1.046, 95% CI: 1.029-1.063) were risk factors for pediatric colorectal polyps in logistic regression analysis. Higher vegetable intake (OR: 0.993, 95% CI: 0.986-1.000) was a protective factor against pediatric colorectal polyps. The area under the curve (AUC) of meat intake in the receiver operating characteristic (ROC) curve analysis for predicting colorectal polyps was 0.607; the best cut-off value was 92.14 g/d (P = 0.010, 95% CI: 0.527-0.687). The meat and vegetable intake combination AUC in predicting pediatric colorectal polyps was 0.781 (P < 0.001, 95% CI: 0.718-0.845). CONCLUSIONS: Juvenile, solitary, and located in the rectosigmoid region polyps are most common in children. Hematochezia is the main clinical manifestation. Most polyps were, but multiple and proximally located polyps were also detected. Age ≤ 6 years, especially 3-6 years, positive family aggregation, positive sIgE, and higher meat intake are risk factors for pediatric colorectal polyps. A higher vegetable intake is a protective factor.

3,4-benzopyrene aggravates myocardial ischemia-reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation.

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.

Transcutaneous electrical acupoint stimulation for the prevention of postoperative delirium in elderly surgical patients: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the preventive effect of transcutaneous electrical acupoint stimulation on postoperative delirium in elderly surgical patients. Methods: PubMed, CENTRAL, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials regarding the effect of transcutaneous electrical acupoint stimulation on preventing postoperative delirium in elderly patients undergoing any type of surgery. The primary outcome was the incidence of postoperative delirium. The secondary outcome was the duration of postoperative delirium. All analyses were conducted using RevMan 5.3 and Stata 13.0 software. Results: Twelve trials with 991 participants were included, and most of them were at high/unclear risk of bias. Meta-analysis showed transcutaneous electrical acupoint stimulation could reduce the incidence of postoperative delirium (RR = 0.40, 95%CI = 0.29 to 0.55, p < 0.00001) and shorten the duration of postoperative delirium (MD = -0.97 days, 95%CI = -1.72 to -0.22, p = 0.01). Subgroup analyses demonstrated that transcutaneous electrical acupoint stimulation reduced the incidence of postoperative delirium in elderly patients undergoing orthopedic surgery and thoracic surgery, but not digestive surgery; transcutaneous electrical acupoint stimulation with dilatational wave and with continuous wave were both beneficial; and transcutaneous electrical acupoint stimulation was favored when compared to blank and sham control. Conclusion: Transcutaneous electrical acupoint stimulation could reduce the incidence of postoperative delirium and shorten the duration of postoperative delirium in elderly surgical patients. The findings should be interpreted with caution due to weak evidence. High-quality, large sample, and multi-center trials are needed to further confirm the preliminary findings.Systematic review registration: https://inplasy.com/inplasy-2022-7-0096/, identifier: INPLASY202270096.

Shexiang Baoxin Pill attenuates myocardial ischemia/reperfusion injury by activating autophagy via modulating the ceRNA-Map3k8 pathway.

BACKGROUND: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. MATERIALS AND METHODS: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 µg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. RESULTS: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1ß and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. CONCLUSION: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.

Cost-Effectiveness Analysis of Gefitinib Alone and Combined with Chemotherapy as First-Line Treatment for Patients with Advanced Non-Small-Cell Lung Cancer.

Background: The rational choice of drugs for treating patients with advanced non-small-cell lung cancer (NSCLC) is significantly impacted by changes in modern drug policy, health insurance negotiation, and budget impact analyses. Here, we provide a basis for rational drug use decisions in clinical practice and promote the widespread use of pharmacoeconomic methods in clinical decision-making based on current drug policies in China and real-world data. Methods: A Markov model was developed to evaluate the health and economic outcomes in patients with advanced NSCLC treated with first-line chemotherapy with gefitinib and gefitinib plus chemotherapy. Clinical data, cost, and utility data were extracted from published literature or real-world data; sensitivity analysis was performed to assess the uncertainty in the results. The results were summarized as QALYs and the ICER. Results: The average cost and QALYs associated with gefitinib and gefitinib plus chemotherapy strategies were $62,882.83 and 1.70 and $84,509.30 and 1.93, respectively. The ICER for gefitinib plus chemotherapy versus gefitinib alone was $95,135.50. The one-way sensitivity analysis showed that the utility value of progressive disease (PD) had the greatest impact on the treatment outcome. Probabilistic sensitivity analysis showed that if China's willingness to pay threshold was $33,300/QALY, the probability of superiority of the gefitinib plus chemotherapy regimen was 0. Conclusion: The study suggests that, from the perspective of the Chinese health system, gefitinib plus chemotherapy is not a cost-effective option for NSCLC patients with EGFR mutations. These findings may help clinicians make the best treatment decisions for patients with NSCLC.

[Application of iPDMS protein microarray in screening of tumor-associated antigen autoantibodies].

The rapid screening of tumor markers is a challenging task for early diagnosis of cancer. This study aims to use highly sensitive chemiluminescent protein microarray technology to efficiently screen a variety of low abundance tumor related markers. A new material, termed integrated polydimethylsiloxane modified silica gel (iPDMS), was obtained by adding a surface polymerization initiator with olefin end to the conventional polydimethylsiloxane, and fixing into the three-dimensional structure of polydimethylsiloxane by thermal crosslinking through silicon hydrogen bonding. In order to make the iPDMS material resistant to non-specific protein adsorption, a poly(OEGMA) polymer brush was synthesized by surface-initiated atom transfer radical polymerization at the active initiation site. Finally, 20 tumor-related antigens were printed into the specific areas of the microarray by high-throughput spray printing technology, and assembled into 48-well detection microtiterplates of the iPDMS microarray. It was found the VEGFR and VEGF121 autoantibodies that obtained from 8 common tumors (breast cancer, lung cancer, colon cancer, gastric cancer, liver cancer, leukemia, lymphoma and ovarian cancer) can be used as potential tumor markers. The chemiluminescence labeled iPDMS protein microarray can be used for the screening of tumor autoantibodies at early stage.

Developmental titanium dioxide nanoparticle exposure induces oxidative stress and neurobehavioral changes in zebrafish.

The widespread commercial application of titanium dioxide nanoparticles (TiO2 NPs) leads to ubiquitous presence of TiO2 NPs in the aquatic environment, which highlights the necessity to determine their potential adverse effects on aquatic organisms. The developing nerve system is particularly susceptible to environment perturbation. However, few studies have explored the developmental neurobehavioral toxicity of TiO2 NPs, especially at smaller particle size ranges (≤20 nm) that have relatively longer retention time in the water column. In this study, zebrafish embryos were exposed to non-teratogenic concentrations of 0.1 and 1 mg/L TiO2 NPs (average size of 14-20 nm) from 8 to 108 h post-fertilization (hpf) followed by various assessments at different time points up to 12 days post-fertilization (dpf). Our findings revealed that 1 mg/L TiO2 NPs perturbed the motor and social behaviors in larval zebrafish. These behavioral changes were characterized by decreased swimming speed in a locomotor response test at 5 dpf, increased travel distance in a flash stimulus test at 5 dpf, increased preference to the light zone in a light/dark preference test at 10 dpf, and increased mirror attack and percent time spent in the mirror zone in a mirror stimulus response assay at 12 dpf. Mechanistic examinations at 5 dpf revealed elevated cell apoptosis and oxidative stress. Cell apoptosis was characterized by increased acridine orange (AO) positive cells in the olfactory region and neuromasts of the lateral line system. Oxidative stress was characterized by increased lipid peroxidation, increased ROS production, and upregulated catalase (cat) gene expression. In addition, TiO2 NP exposure also upregulated genes associated with the developmental nervous system such as the growth associated protein 43 (gap43) and proliferating cell nuclear antigen (pcna). Our results suggest that the neurobehavioral changes in larvae exposed to 1 mg/L TiO2 NPs during early development may result from cell apoptosis and oxidative stress induced neuronal damages.

Differentiated cancer cell-originated lactate promotes the self-renewal of cancer stem cells in patient-derived colorectal cancer organoids.

Tumors harbor diverse compartments of cells with distinct metabolic properties and phenotypes, but the mechanism by which metabolic commensalism among distinct subsets of cancer cells affects tumor progression remains unclear. Colorectal cancer (CRC) has been reported to consist of cancer stem cells (CSCs) and differentiated cancer cells (non-CSCs). In the present study, organoid models were employed to show that CSCs and non-CSCs in CRC were characterized by distinct metabolic phenotypes. Treatment with either non-CSC-derived conditioned medium or exogenous lactate enhanced organoid-forming and tumor-initiating capacity of CSCs. In tumor regeneration assays with co-implanted CSCs and non-CSCs, the tumor-initiating activity was reduced when either monocarboxylate transporter (MCT)4 in non-CSCs or MCT1 in CSCs was silenced or inhibited. Mechanistically, oxiadative phosphorylation-derived reactive oxygen species in CSCs activated AKT-Wnt/ß-catenin signaling, which could be induced by lactate from non-CSCs. Overall, these results suggest that CSCs and non-CSCs possess distinct metabolic profiles and, unexpectedly, non-CSC-originated lactate promotes self-renewal of CSCs and thus contributes to CRC progression. Our findings establish a rationale for developing novel therapies targeting the metabolic commensalism between different cell populations in CRC.

Hypoxic colorectal cancer cells promote metastasis of normoxic cancer cells depending on IL-8/p65 signaling pathway.

Tumor heterogeneity is an important feature of malignant tumors, and cell subpopulations may positively interact to facilitate tumor progression. Studies have shown that hypoxic cancer cells possess enhanced metastatic capacity. However, it is still unclear whether hypoxic cancer cells may promote the metastasis of normoxic cells, which have greater access to the blood circulation. When cocultured with hypoxic CRC cells or treated with hypoxic CRC cell-derived CM, normoxic CRC cells possessed increased metastatic capacity. Furthermore, hypoxic CRC cell-derived CM was enriched in interleukin 8. Hypoxic CRC cell-derived CM and recombinant human IL-8 both enhanced the metastatic capacity of normoxic cells by increasing the phosphorylation of p65 and then by inducing epithelial-mesenchymal transition. Knockdown of IL-8 in hypoxic CRC cells or the use of an anti-IL-8 antibody attenuated the CM- or rhIL-8-induced prometastatic capacity of normoxic CRC cells. Inhibition or knockdown of p65 abrogated IL-8-induced prometastatic effects. Most importantly, hypoxia-treated xenograft tumors enhanced the metastasis of normoxic CRC cells. Hypoxic CRC cell-derived IL-8 promotes the metastatic capacity of normoxic cells, and novel therapies targeting the positive interactions between hypoxic and normoxic cells should be developed.

Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

Engineering of biomaterials for tumor modeling.

Development of biomaterials mimicking tumor and its microenvironment has recently emerged for the use of drug discovery, precision medicine, and cancer biology. These biomimetic models have developed by reconstituting tumor and stroma cells within the 3D extracellular matrix. The models are recently extended to recapitulate the in vivo tumor microenvironment, including biological, chemical, and mechanical conditions tailored for specific cancer type and its microenvironment. In spite of the recent emergence of various innovative engineered tumor models, many of these models are still early stage to be adapted for cancer research. In this article, we review the current status of biomaterials engineering for tumor models considering three main aspects - cellular engineering, matrix engineering, and engineering for microenvironmental conditions. Considering cancer-specific variability in these aspects, our discussion is focused on pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC). In addition, we further discussed the current challenges and future opportunities to create reliable and relevant tumor models.

Sphere­forming assay vs. organoid culture: Determining long­term stemness and the chemoresistant capacity of primary colorectal cancer cells.

Three­dimensional (3D) cultures are indispensable for capturing tumor heterogeneity in colorectal cancer (CRC) in vitro. Although 3D cultures (such as sphere­forming assay and organoid culture) can partially preserve the morphological and molecular characteristics of primary CRC, whether these 3D cultures maintain the long­term stemness of cancer stem cells (CSCs) remains largely unknown. In the present study, spheres and organoids were generated side by side using individual primary CRC specimens, then respectively processed as serial passages. The results revealed that during serial passages, the percentage of CSCs (such as cluster of differentiation­133+ and Wnt+ cells) in organoids and the tumor­initiating capacity of organoid­derived cells were constant, while they gradually increased in the sphere­derived cells. Furthermore, during serial passages, resistance to chemotherapeutic agents (including 5­fluorouracil and oxaliplatin) in sphere­ and organoid­derived cells was evaluated. The results indicated that the percentage of chemoresistant cells was constant in serial organoid cultures; however, it gradually increased in the serial sphere­forming assays. Taken together, the results of the present study comprehensively demonstrate that, with regard to long­term culture in vitro, organoid culture may be useful in maintaining tumor heterogeneity and the levels of chemoresistant cells, while the sphere formation assay enriches for CSCs and chemoresistant cells.

Astragaloside IV Attenuated 3,4-Benzopyrene-Induced Abdominal Aortic Aneurysm by Ameliorating Macrophage-Mediated Inflammation.

Abdominal aortic aneurysm (AAA), characterized by macrophage infiltration-mediated inflammation and oxidative stress, is a potentially fatal disease. Astragaloside IV (AS-IV) has been acknowledged to exhibit antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of AS-IV against AAA formation induced by 3,4-benzopyrene (Bap) and angiotensin II (Ang II), and to explore probable mechanisms. Results showed that AS-IV decreased AAA formation, and reduced macrophage infiltration and expression of matrix metalloproteinase. Furthermore, AS-IV abrogated Bap-/Ang II-induced NF-κB activation and oxidative stress. In vitro, AS-IV inhibition of macrophage activation and NF-κB was correlated with increased phosphorylation of phosphatidylinositol 3-kinase (PI3-K)/AKT. Together, our findings suggest that AS-IV has potential as an intervention in the formation of AAA. HIGHLIGHTS: (1)The protective effect of Astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) is associated with its suppressing effects on inflammation in the aortic wall.(2)AS-IV abrogated 3,4-benzopyrene (Bap)/angiotensin II (Ang II)-induced nuclear factor-κB (NF-κB) activation and oxidative stress.(3)AS-IV inhibited Bap-induced RAW264.7 macrophage cells activation by inhibiting oxidative stress and NF-κB activation through phosphatidylinositol 3-kinase (PI3-K)/AKT pathway.AS-IV is a potential preventive agent for cigarette smoking-related AAA.

Significance of aquaporins' expression in the prognosis of gastric cancer.

Gastric carcinoma is one of the most lethal malignancy at present with leading cause of cancer-related deaths worldwide. Aquaporins (AQPs) are a family of small, integral membrane proteins, which have been evidenced to play a crucial role in cell migration and proliferation of different cancer cells including gastric cancers. However, the aberrant expression of specific AQPs and its correlation to detect predictive and prognostic significance in gastric cancer remains elusive. In the present study, we comprehensively explored immunohistochemistry based map of protein expression profiles in normal tissues, cancer and cell lines from publicly available Human Protein Atlas (HPA) database. Moreover, to improve our understanding of general gastric biology and guide to find novel predictive prognostic gastric cancer biomarker, we also retrieved 'The Kaplan-Meier plotter' (KM plotter) online database with specific AQPs mRNA to overall survival (OS) in different clinicopathological features. We revealed that ubiquitous expression of AQPs protein can be effective tools to generate gastric cancer biomarker. Furthermore, high level AQP3, AQP9, and AQP11 mRNA expression were correlated with better OS in all gastric patients, whereas AQP0, AQP1, AQP4, AQP5, AQP6, AQP8, and AQP10 mRNA expression were associated with poor OS. With regard to the clinicopathological features including Laurens classification, clinical stage, human epidermal growth factor receptor 2 (HER2) status, and different treatment strategy, we could illustrate significant role of individual AQP mRNA expression in the prognosis of gastric cancer patients. Thus, our results indicated that AQP's protein and mRNA expression in gastric cancer patients provide effective role to predict prognosis and act as an essential agent to therapeutic strategy.

Microarray Analysis Reveals a Potential Role of lncRNA Expression in 3,4-Benzopyrene/Angiotensin II-Activated Macrophage in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a fatal disease, and exposure to 3,4-benzopyrene (Bap) is closely related to the development of AAA. We have found that Bap could impair the biological function of endothelial progenitor cells (EPCs), which are associated with the occurrence of AAA. We have also demonstrated that macrophage activation plays a key role in Bap-induced AAA, but the mechanism is unknown. Here, we used a mouse lncRNA array to investigate the expression signatures of lncRNAs and mRNAs in Bap-activated macrophage. A total of 457 lncRNAs and 219 mRNAs were found to be differentially expressed. The function of differential mRNAs was determined by pathway and Gene Ontology analysis. Eight pathways associated with inflammation were upregulated, and seven pathways including cell apoptosis were downregulated. It was worth noting that AGE-RAGE pathway, which was involved in Bap-induced EPC dysfunction, was significantly upregulated in Bap-activated macrophage and may contribute to AAA formation. Thus, lncRNAs may exert a key role in activated macrophages and intervene the core lncRNAs and may inhibit the occurrence of a series of cascade reactions in the macrophages, which may provide potential targets for AAA caused by smoking.