Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation

BACKGROUND: Aortic aneurysm is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Activation of prostaglandin E(2) (PGE(2)) is known to increase the expression of matrix metalloproteinase (MMP) and the release of inflammatory cytokines, and may thus exacerbate abdominal aortic aneurysm (AAA) formation. We hypothesized that selective blocking of PGE(2), in particular, EP4 prostanoid receptor signaling, would attenuate the development of AAA. METHODS AND FINDINGS: Immunohistochemical analysis of human AAA tissues demonstrated that EP4 expression was greater in AAA areas than that in non-diseased areas. Interestingly, EP4 expression was proportional to the degree of elastic fiber degradation. In cultured human aortic smooth muscle cells (ASMCs), PGE(2) stimulation increased EP4 protein expression (1.4 ± 0.08-fold), and EP4 stimulation with ONO-AE1-329 increased MMP-2 activity and interleukin-6 (IL-6) production (1.4 ± 0.03- and 1.7 ± 0.14-fold, respectively, P<0.05). Accordingly, we examined the effect of EP4 inhibition in an ApoE(-/-) mouse model of AAA infused with angiotensin II. Oral administration of ONO-AE3-208 (0.01-0.5 mg/kg/day), an EP4 antagonist, for 4 weeks significantly decreased the formation of AAA (45-87% reduction, P<0.05). Similarly, EP4(+/-)/ApoE(-/-) mice exhibited significantly less AAA formation than EP4(+/+)/ApoE(-/-) mice (76% reduction, P<0.01). AAA formation induced by periaortic CaCl(2) application was also reduced in EP4(+/-) mice compared with wild-type mice (73% reduction, P<0.001). Furthermore, in human AAA tissue organ cultures containing SMCs and macrophages, doses of the EP4 antagonist at 10-100 nM decreased MMP-2 activation and IL-6 production (0.6 ± 0.06- and 0.7 ± 0.06-fold, respectively, P<0.05) without increasing MMP-9 activity or MCP-1 secretion. Thus, either pharmacological or genetic EP4 inhibition attenuated AAA formation in multiple mouse and human models by lowering MMP activity and cytokine release. CONCLUSION: An EP4 antagonist that prevents the activation of MMP and thereby inhibits the degradation of aortic elastic fiber may serve as a new strategy for medical treatment of AAA

Enhancement of the Antihypertensive Effect of Fermented Sargassum horneri with Lactiplantibacillus pentosus SN001

Sargassum horneri is a seaweed with antihypertensive properties. However, it is underutilized in some areas, and effective utilization methods are being sought. In this study, we prepared a fermented S. horneri using lactic acid bacteria Lactiplantibacillus pentosus SN001 and investigated its effective utilization by enhancing its antihypertensive effect. The ACE inhibitory activity of S. horneri ranged from 3.6% to a maximum of 63.3% after fermentation. In vivo studies using mice and spontaneously hypertensive rats (SHR) suggested an antihypertensive effect of fermented S. horneri. Purification and NMR analysis of the ACE inhibitory component in fermented S. horneri identified glycerol. Therefore, it is suggested that glycerol is responsible for the strong antihypertensive effect of fermented S. horneri. In conclusion, S. horneri is expected to be used as a dietary ingredient with enhanced antihypertensive effect by fermentation with L. pentosus SN001

Enhancement of the Antihypertensive Effect of Fermented <i>Sargassum horneri</i> with <i>Lactiplantibacillus pentosus</i> SN001

Sargassum horneri is a seaweed with antihypertensive properties. However, it is underutilized in some areas, and effective utilization methods are being sought. In this study, we prepared a fermented S. horneri using lactic acid bacteria Lactiplantibacillus pentosus SN001 and investigated its effective utilization by enhancing its antihypertensive effect. The ACE inhibitory activity of S. horneri ranged from 3.6% to a maximum of 63.3% after fermentation. In vivo studies using mice and spontaneously hypertensive rats (SHR) suggested an antihypertensive effect of fermented S. horneri. Purification and NMR analysis of the ACE inhibitory component in fermented S. horneri identified glycerol. Therefore, it is suggested that glycerol is responsible for the strong antihypertensive effect of fermented S. horneri. In conclusion, S. horneri is expected to be used as a dietary ingredient with enhanced antihypertensive effect by fermentation with L. pentosus SN001

Role of Nurses in Early Ambulation of Living Donor Liver Transplant Recipients

［Introduction］ Liver transplant recipients suffer more complications than do patients undergoing other gastroenterological surgeries. Many factors inhibit ambulation in liver transplant patients, such as the level of restriction to bed rest and length of stay in the intensive care unit（ ICU）. Patients thus face ambulation difficulties. Support for ambulation is one of the major daily tasks of nurses. We reviewed the ambulation situations of patients who underwent living donor liver transplantation to investigate factors that contributed to ambulation and the nurse’s role therein. ［Patients］ Ten recipients underwent living donor liver transplantation in our hospital between April 2009 and December 2010. Records of the 8 patients who survived were evaluated for this study. ［Result］ According to the postoperative day of initiation of independent walking in the hospital ward, there were no significance difference among operation time, intraoperative bleeding, length of stay in ICU, bed rest level, complications, and rehabilitation intervention. However, the patients who received preoperative guidance were more highly motivated about ambulation than were patients who did not receive preoperative guidance. ［Discussion］ Although initiation of independent walking in the hospital ward differed depending on the patient's general status, it was found that volition is also a strong factor in patient ambulation. Preoperative orientation helps patients to understand perioperative management and clinical course. Moreover, it is necessary to share information with the rehabilitation team and to assist in the activities of daily living for early ambulation

Additional file 1 of Vaccination status, incidence of adverse events, and awareness of COVID-19 vaccine among outpatients undergoing chemotherapy

Additional file 1: Survey item