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Highlights • NK-1R is expressed in HAECs and HUVECs and upregulated in response to ox-LDL. • Aprepitant inhibits attachment of monocytes to HAECs by reducing vcam-1, E-selectin. • Aprepitant promotes KLF-2/eNOS/NO signaling by activating ERK5. • Effects of Aprepitant on cell adhesion, vcam-1, and E-selectin are dependent on KLF2. Abstract Atherosclerosis is the main cause of many cardiovascular diseases. Endothelial dysfunction is recognized as an early event in the development of atherosclerosis. Many drugs have been studied to mitigate hyperlipidemia-induced endothelial injury. Studies have demonstrated that neuropeptide substance P (SP) and its preferred receptor neurokinin receptor 1 (NK-1R) are involved in the pathological progression of cardiovascular disease. In this study, we show that aprepitant, a selective NK-1R antagonist, possesses beneficial effects that protect endothelial cells from oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and injury. Our data demonstrate that NK-1R is expressed in both aortic and vein-originated endothelial cells and that ox-LDL treatment induces NK-1R expression. Treatment with aprepitant suppresses induction of endothelial vascular adhesion molecule (VCAM-1 and E-selectin) and cytokine by ox-LDL. The presence of aprepitant mitigates adhesion of monocytes to endothelial cells and the reduction in eNOS/NO triggered by ox-LDL. Mechanistically, we demonstrate that aprepitant suppresses ERK5-KLF2 axis activation. Silencing of KLF2 abolishes the inhibitory role of aprepitant on ox-LDL-induced inflammatory response, suggesting that its action is dependent on KLF2. Collectively, our data support that aprepitant exerts an anti-inflammatory effect. Further research is required to investigate the therapeutic potential of aprepitant in vascular inflammation resulting from atherosclerosis. [ABSTRACT FROM AUTHOR]

Resources and environment provide the fundamental conditions for human life. With the rapid growth of population and development of regional social economies, the environment and ecosystems have been disturbed to varying degrees. Contradictions among human beings, resources and environment have become a key issue restricting the sustainable development, particularly in arid and semiarid regions. This study takes the arid and semiarid region of Xinjiang, China, as an example. An evaluation model and index system of resource and environmental carrying capacity (RECC) are proposed based on the "pressure-vulnerability-adaptability" (PVA) concept. The RECCs in Xinjiang from 2000 to 2019 were quantitatively evaluated, and the reasons for the spatio-temporal changes of RECC were explored. In addition, the ordered weighted averaging (OWA) algorithm was introduced to realize multi-scenario simulations with concerning different decision-making preferences. Results indicated that: (1) the RECC in Xinjiang presents a spatial pattern of "high pressure around the three mountains and low pressure around the two basins" and the area of high carrying capacity decreased significantly from 2000 to 2019; (2) the pressure risk indicators are key factors in evaluating the RECC and the difference between the regional RECC and pressure risk is largely affected by vulnerability and adaptability; (3) the future regional RECC are predicted differently under different development orientations via the OWA algorithm, which is useful to provide decision-making references for promoting sustainable development. • The RECC evaluation model and index system for arid and semiarid regions were proposed. • The reasons for the spatio-temporal changes of RECC were explored. • The spatial difference between the RECC and the pressure was apparent. • Multi-scenario simulations of the RECC through the OWA can provide guidance for sustainable development. [ABSTRACT FROM AUTHOR]

Abstract: Bladder cancer is one of the most common tumors of the genitourinary tract; however, the molecular events underlying growth and invasion of the tumor remain unclear. Here, role of the CXCR7 receptor in bladder cancer was further explored. CXCR7 protein expression was examined using high-density tissue microarrays. Expression of CXCR7 showed strong epithelial staining that correlated with bladder cancer progression. In vitro and in vivo studies in bladder cancer cell lines suggested that alterations in CXCR7 expression were associated with the activities of proliferation, apoptosis, migration, invasion, angiogenesis and tumor growth. Moreover, CXCR7 expression was able to regulate expression of the proangiogenic factors IL-8 or VEGF, which may involve in the regulation of tumor angiogenesis. Finally, we found that signaling by the CXCR7 in bladder cancer cells activates AKT, ERK and STAT3 pathways. The AKT and ERK pathways may reciprocally regulate, which are responsible for in vitro and in vivo epithelial to mesenchymal transition (EMT) process of bladder cancer. Simultaneously targeting the two pathways by using U0126 and LY294002 inhibitors or using CCX733, a selective CXCR7 antagonist drastically reduced CXCR7-induced EMT process. Taken together, our data show for the first time that CXCR7 plays a role in the development of bladder cancer. Targeting CXCR7 or its downstream-activated AKT and ERK pathways may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for bladder cancer. [Copyright &y& Elsevier]

The long non-coding RNA (lncRNA) OGFRP1 has been found to promote malignancy in prostate cancer (PC) and other cancer types. How this lncRNA functions in the regulation of PC chemoresistance, however, is poorly defined. qRT-PCR was employed to measure OGFRP1, miR-149-5p, and IL-6 expression in PC tissues and cells. IC50 values for paclitaxel and docetaxel in PC cells were assessed via a CCK-8 assay approach. Putative miR-149-5p binding targets were identified and validated through bioinformatics assays and luciferase reporter assays, respectively. The impact of OGFRP1 on PC chemoresistance in vivo was validated using a xenograft model system. Docetaxel-resistant PC (PC/DR) cells and tissues exhibited reduced OGFRP1 expression and increased miR-149-5p expression. Knocking down OGFRP1 augmented the sensitivity of these PC cells to docetaxel and paclitaxel in vitro and in vivo. Mechanistically, OGFRP1 was found to bind and sequester miR-149-5p within PC/DR cells, thereby indirectly regulating IL-6 expression. Consistent with this model, the overexpression of IL-6 reversed the OGFRP1 knockdown-mediated reductions in docetaxel and paclitaxel IC50 values for these PC cells. OGFRP1 can sequester miR-149-5p, thereby indirectly promoting IL-6 upregulation and thereby promoting chemoresistance in PC cells. This OGFRP1/miR-149-5p/IL-6 axis may thus be a promising target for therapeutic efforts aimed at PC chemosensitization and treatment. [ABSTRACT FROM AUTHOR]

Pedicularis kansuensis is a poisonous grass and a semi-parasitic plant that has spread rapidly in alpine grasslands in recent years and caused great harm to animal husbandry and the ecological environment. However, little is known about the habitat of P. kansuensis and the key environmental factors that influence its expansion. We assessed the potential impact of climate change on the distribution of P. kansuensis in China under representative concentration pathway (RCP) 2.6 and RCP 8.5 using maximum entropy (MaxEnt) and MigClim for the years 2050 and 2070 and examined key environmental factors affecting P. kansuensis distribution. In total, 118 occurrence points and fourteen selected variables were used for the modeling. The models developed for P. kansuensis showed excellent performance (AUC > 0.9 and TSS > 0.90). The results were as follows. 1) The occupied habitats for P. kansuensis in the four climate scenarios were generally offset in the northward direction. 2) The most important environmental variables influencing the spread of P. kansuensis were altitude, annual precipitation, annual temperature range, precipitation in the warmest quarter and ultraviolet-B radiation seasonality (UVB-2). 3) Under RCP 2.6, the occupied habitat would be increased 0.04% by 2050 and would be increased to 0.51% by 2070. Under RCP 8.5, the average occupied habitat was predicted to increase 0.07% by 2050 and increase to 0.53% by 2070. The increase was relatively higher in the occupied habitats located in the southwestern regions (Sichuan, Xizang and Yunnan) than those in the northwestern regions (Gansu and Xinjiang). Unlabelled Image • We predicted the distribution of P. kansuensis in China by MaxEnt and MigClim. • Altitude and annual precipitation were the most critical factors shaping P. kansuensis distribution. • The occupied habitat of P. kansuensis was expended in climate scenario with RCP2.6 and RCP 8.5. • In the future, the occupied habitat of P. kansuensis was generally shifted northward. [ABSTRACT FROM AUTHOR]