Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower ...levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP‐13) expression are higher in prostate cancer patients than in healthy cancer‐free individuals. Mechanistic investigations revealed that melatonin inhibits MMP‐13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c‐Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP‐13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.
Melatonin acts on the MT1 receptor and inhibits phospholipase C (PLC) and p38 signal cascades, subsequently suppresses matrix metallopeptidase 13 (MMP‐13) expression through the c‐Jun‐dependent pathway, leading to the reduction of prostate cancer metastasis. This is the first indication that melatonin impedes metastasis via the targeting of MMP‐13 in prostate cancer cells, based on evidence from basic and clinical studies.
Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from
(commonly known as Niu-Chang-Chih), which ...has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.
Algal reefs, concreted by crustose coralline algae (CCA), are the main biotic reefs in temperate waters but rare in the subtropics and tropics. The world's largest known intertidal algal reef in the ...subtropics is the Taoyuan Algal Reef (TAR) located in the northwestern coast of Taiwan. The biodiversity and ecology of the TAR are scarcely explored, and now the reef is imperiled by industrialization. Here, we document cryptic species of CCA in Taiwan, particularly the TAR, by sequencing the psbA genes of over 1800 specimens collected across Taiwan. We also examine the ecological background of the TAR by surveying its benthic composition and measuring its environmental parameters. Our data reveal that the TAR harbours a high diversity of cryptic CCA species (27 molecular operational taxonomic units, or mOTUs), many of which are potentially new to science (18 mOTUs) and/or endemic to the TAR (9 mOTUs). Comparing the CCA species inventory of the TAR with the rest of Taiwan shows that the TAR represents a unique hotspot of CCA taxa in the waters of Taiwan. Our analyses show that variation in the CCA assemblages in the TAR is associated with geographic distance, sedimentation, and substrate type (for example, reef vs. hermit crab shell), suggesting that dispersal limitation and contemporary environmental selection shape the CCA assemblages in the TAR. The data from this study can inform the monitoring of human impacts on the health of the TAR and contribute to our understanding of the ecological processes underlying algal reef development.
Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell ...growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti‑tumor agent for the treatment of gingival cancer.
The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in ...diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools.
This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992-2003; Group B: 2004-2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups.
Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A.
Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.
El Niños (EN) are known to decay more rapidly, while La Niñas (LN) tend to decay more slowly. Observational analyses and coupled model experiments are conducted to show that sea surface temperature ...(SST) anomalies over the subtropical northeastern Pacific (SNEP) and equatorial western Pacific (EWP) are key factors to determine the decay pace of the EN and LN and their asymmetry. In the present climate the LN produces larger cold SST anomalies over the regions than the warm SST anomalies produced by the EN. The magnitude difference over the SNEP and EWP helps to slow down the LN decay via subtropical footprinting and tropical thermocline variation mechanisms, respectively. Coupled Model Intercomparison Project Phase 6 models project the magnitude differences of SNEP SST anomalies between EN and LN to reduce in the future warming world, causing the asymmetric EN‐LN decay to weaken.
Plain Language Summary
There are obvious asymmetric features in mature winter and decaying summer between the warm (El Niño EN) and cold phases (La Niña LN) of El Niño‐Southern Oscillation (ENSO). Cold sea surface temperature (SST) anomalies over the subtropical northeastern Pacific (SNEP) and equatorial western Pacific (EWP) in winter are larger in amplitude during LN than EN. This asymmetric feature in winter enables the LN to delay slower and last longer than the EN in the following summer, which is another asymmetric feature between these two phases of the ENSO. The large cold anomalies over the SNEP can spread to the equatorial Pacific to slow down the LN decay through subtropical ocean‐atmosphere coupling processes. The large cold anomalies over the EWP also contribute to the slow decay of LN but mainly through tropical ocean‐atmosphere coupling processes. Climate models project that the future global warming may reduce the magnitude differences of the SNEP SST anomalies between EN and LN and cause a rapid decline of LN in a warmer world.
Key Points
The slow La Niña and rapid El Niño decays are caused by differences in their anomalies over the subtropical and tropical Pacific
The subtropical (tropical) anomalies activate a seasonal footprinting (thermocline variation) mechanism to affect the decay pace
The asymmetric decay is projected to decrease in the future warming world due to the reduction of the subtropical anomaly difference
The proportion of students studying in higher education institutions who are experiencing mental health needs is increasing and becoming a serious concern. Using participatory arts projects may be ...key to enabling students to maintain well‐being despite the pressures inherent in their student role. Therefore, this study aimed to ascertain whether such a course could be feasibly developed within a university setting, and to examine how esthetic experience influences university students' well‐being. To understand the differences in students' esthetic experience and well‐being before and after engaging in participatory art, this study implemented an intervention and collected quantitative and qualitative data. A total of 39 students volunteered to participate in the study. The results revealed that esthetic experience predicted student well‐being, as the more students had an esthetic experience by concentrating on a particular artwork, the more effective it was in terms of enhancing their well‐being. In addition, there was a significant difference between the pre‐ and postintervention, where students' esthetic experience and well‐being improved after completing the art activities. These findings have implications for our understanding of university students' well‐being, as well as the importance of considering participatory art, on its own, as a target for intervention.
Practitioner Points
Esthetic experience predicted college students' well‐being.
There was a significant difference between the pre‐ and postintervention, with the college students' esthetic experience and well‐being improving after completing the art activities.
Participatory arts contributed to both esthetic experience and well‐being.
Abstract Background Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) ...are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo. Result The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11–7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects. Conclusion These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.
The CXC chemokine ligand‐13 (CXCL13) is a chemoattractant of B cells and has been implicated in the progression of many cancers. So far, CXCL13 and its related receptor CXCR5 have been proved to ...regulate cancer cell migration as well as tumour metastasis. However, the role of CXCL13‐CXCR5 axis in metastasis of lung cancer is still poorly understood. In this study, we found that CXCL13 and CXCR5 were commonly up‐regulated in lung cancer specimens compared with normal tissues among different cohorts. Our evidence showed that CXCL13 obviously promoted migration of lung cancer cells, and this effect was mediated by vascular cell adhesion molecule‐1 (VCAM‐1) expression. We also confirmed that CXCR5, the major receptor responsible for CXCL13 function, was required for CXCL13‐promoted cell migration. We also test the candidate components which are activated after CXCL13 treatment and found that phospholipase C‐β (PLCβ), protein kinase C‐α (PKCα) and c‐Src signalling pathways were involved in CXCL13‐promoted cell migration and VCAM‐1 expression in lung cancer cells. Finally, CXCL13 stimulated NF‐κB transcription factor in lung cancer cells, contributing to VCAM‐1 expression in translational level. These evidences propose a novel insight into lung cancer metastasis which is regulated by CXCL13.
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