Gravesenkoch0665

Recurrence and metastasis remain the major cause of cancer mortality. Even for early-stage lung cancer, adjuvant chemotherapy yields merely slight increase to patient survival. EF-hand domain-containing protein D2 (EFHD2) has recently been implicated in recurrence of patients with stage I lung adenocarcinoma. In this study, we investigated the correlation between EFHD2 and chemoresistance in non-small cell lung cancer (NSCLC). High expression of EFHD2 was significantly associated with poor overall survival of NSCLC patients with chemotherapy in in silica analysis. Ectopic EFHD2 overexpression increased cisplatin resistance, whereas EFHD2 knockdown improved chemoresponse. Mechanistically, EFHD2 induced the production of NADPH oxidase 4 (NOX4) and in turn the increase of intracellular reactive oxygen species (ROS), consequently activating membrane expression of the ATP-binding cassette subfamily C member 1 (ABCC1) for drug efflux. Non-steroidal anti-inflammatory drug (NSAID) ibuprofen suppressed EFHD2 expression by leading to the proteasomal and lysosomal degradation of EFHD2 through a cyclooxygenase (COX)-independent mechanism. Combining ibuprofen with cisplatin enhanced antitumor responsiveness in a murine xenograft model in comparison with the individual treatment. In conclusion, we demonstrate that EFHD2 promotes chemoresistance through the NOX4-ROS-ABCC1 axis and therefore developing EFHD2-targeting strategies may offer a new avenue to improve adjuvant chemotherapy of lung cancer.Aldehydes are implicated in the development of hypertension. Trans, trans-2,4-decadienal (tt-DDE), a dietary α,β-unsaturated aldehyde, is widespread in many food products. However, the role of tt-DDE in the pathophysiology of hypertension remains unknown. This study was designed to investigate whether tt-DDE consumption evokes hypertension and to explore the mechanisms underlying such a role. Sprague-Dawley rats were administered different concentrations of tt-DDE. After 28 days, blood pressure and endothelial function of mesenteric arteries were measured. Results showed that tt-DDE treatment significantly increased blood pressure and impaired endothelial function based on endothelium-dependent vasorelaxation and p-VASP levels. Mechanistically, tt-DDE induced oxidative/nitrative stress in the arteries of rats as evidenced by overproductions of superoxide and peroxynitrite, accompanied with increased expressions of iNOS and gp91phox. To further investigate the effects of tt-DDE on endothelial cells and underlying mechanisms, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of tt-DDE. learn more tt-DDE induced oxidative/nitrative stress in HUVECs. Moreover, tt-DDE induced endothelial cells apoptosis through JNK-mediated signaling pathway. These results show, for the first time, that oral intake of tt-DDE elevates blood pressure and induces endothelial dysfunction in rats through oxidative/nitrative stress and JNK-mediated apoptosis signaling, indicating that excess ingestion of tt-DDE is a potential risk factor for endothelial dysfunction and hypertension.Purpose This study aimed to measure the eye lens doses received by physicians and other medical staff participating in non-vascular imaging and interventional radiology procedures in Japan. Material and methods From October 2014 to March 2017, 34 physicians and 29 other medical staff engaged in non-vascular imaging and interventional radiology procedures at 18 Japanese medical facilities. These professionals wore radioprotective lead glasses equipped with small, optically stimulated luminescence dosimeters and additional personal dosimeters at the neck during a 1-month monitoring period. The Hp(3) and the Hp(10) and Hp(0.07) were obtained from these devices, respectively. The monthly Hp(3), Hp(10), and Hp(0.07) for each physician and other medical staff member were then rescaled to a 12-month period to enable comparisons with the revised occupational equivalent dose limit for the eye lens. Results Among physicians, the average annual Hp(3) values measured by the small luminescence dosimeters on radioprotective glasses were 25.5 ± 38.3 mSv/y (range 0.4-166.8 mSv/y) and 9.3 ± 16.6 mSv/y (range 0.3-82.4 mSv/y) on the left and right sides, respectively. The corresponding values for other medical staff were 3.7 ± 3.1 mSv/y (range 0.4-10.4 mSv/y) and 3.2 ± 2.7 mSv/y (range 0.5-11.5 mSv/y), respectively. Conclusions The eye lens doses incurred by physicians and other medical staff who engaged in non-vascular imaging and interventional radiology procedures in Japan were provided. Physicians should wear radioprotective glasses and use additional radioprotective devices to reduce the amount of eye lens doses they receive.Background and objectives More knowledge is needed of the effectiveness of complex interventions that aim to promote the wellbeing of older people. This study examines the effects of 'participatory group-based care management' conducted among community-dwelling older adults living alone in Central and Eastern Finland. The intervention aimed to promote wellbeing and quality of life (QoL) using a needs-based and participatory approach. Methods The study was carried out as a randomized control trial (intervention group n = 185, control group n = 207). In this article, baseline and 6-month follow-up surveys were used. QoL (WHOQOL-Bref instrument), loneliness (Revised UCLA Loneliness Scale; single-item question), and trust (two items of generalized trust and six items of institutional trust) were used as outcome measurements, and generalized estimating equations (GEE) modeling as the analysis method. Both per-protocol and intention-to-treat analyses were applied. Results According to the per-protocol analysis, the intervention had no effects on QoL. Loneliness decreased among older people with poor QoL at the baseline. Additionally, the intervention enhanced trust in other people and some dimensions of institutional trust. The intention-to-treat analysis did not result in any significant effects on QoL or loneliness, but some small positive changes in institutional trust were found. Conclusions Based on some evidence of small positive effects, the intervention may be beneficial in alleviating loneliness and enhancing trust among older people living alone. Because of the contradictory results, more research is needed to examine the complexity of 'participatory group-based care management´ from the perspective of process evaluation.