A randomised controlled trial on roles of prostaglandin E1 nebulization among patients undergoing one lung ventilation

Background Prostaglandin E1 (PGE1) has been reported to maintain adequate oxygenation among patients under 60% FiO2 one-lung ventilation (OLV). This research aimed to explore whether PGE1 is safe in pulmonary shunt and oxygenation under 40% FiO2 OLV and provide a reference concentration of PGE1. Methods Totally 90 esophageal cancer patients treated with thoracotomy were enrolled in this study, randomly divided into three groups (n = 30/group): Group A (60% FiO2 and 0.1 µg/kg PGE1), Group B (40% FiO2 and 0.1 µg/kg PGE1), and Group C (40% FiO2, 0.2 µg/kg PGE1). Primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included oxidative stress after OLV. Results During OLV, patients in Group C and B had lower levels of PaO2, SaO2, SpO2, MAP, and Qs/Qt than those in Group A (P < 0.05). At T2 (OLV 10 min), patients in Group C and B exhibited a lower level of PaO2/FiO2 than those in Group A, without any statistical difference at other time points. The IL-6 levels of patients in different groups were different at T8 (F = 3.431, P = 0.038), with IL-6 in Group C being lower than that in Group B and A. MDA levels among the three groups differed at T5 (F = 4.692, P = 0.012) and T7 (F = 5.906, P = 0.004), with the MDA level of Group C being lower than that of Group B and A at T5, and the MDA level of Group C and B being lower than that of Group A at T7. In terms of TNF-α level, patients in Group C had a lower level than those in Group B and A at T8 (F = 3.598, P = 0.033). Compared with patients who did not use PGE1, patients in Group C had comparable complications and lung infection scores. Conclusion The concentration of FiO2 could be reduced from 60 to 40% to maintain oxygenation. 40% FiO2 + 0.2 µg/kg PGE1 is recommended as a better combination on account of its effects on the inflammatory factors. Trial registration: Chictr.org.cn identifier: ChiCTR1800018288, 09/09/2018.

Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation

Aims Pathological cardiac hypertrophy induced by activation of the renin–angiotensin–aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. Methods and results Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E prostanoid (EP)3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. Conclusion In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1–MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy. FUNDunding Acknowledgement Type of funding sources: None.

Effects of Prostaglandin E1 and Supplemental Oxygen on the Wound Healing

Background: When an avulsion wound is combined with a crushing injury or when a local flap is moved with significant tension, poor local blood supply may result in partial or complete necrosis of the involved tissue. This paper explores procedures to prevent tissue necrosis for the ischemic wounds.Methods: From March 2017 to December 2018, 29 hospitalized patients (group A) were treated with simple dressing change and administration of antibiotics. From January 2019 to October 2020, 29 hospitalized patients (group B) were injected for the first 3 days intravenously once a day with 50 μg of stabilized prostaglandin E1. Prostaglandin E1 injections were combined with supplemental oxygen (4 L/min through nasal cannula for 24 hours per day for the first 3 days). Wound dressing and antibiotics administration were also combined.Results: Ten patients in group A developed partial wound necrosis, out of which four patients received local flap surgery after excision of the necrotic tissue. The average recovery time was 9.7 days. In group B, four patients developed partial wound necrosis, out of which one was treated with local flap surgery. The average recovery for the four patients in group B took 6.2 days.Conclusion: Prostaglandin E1 and supplemental oxygen reduced the incidence of partial wound necrosis of ischemic wounds and local flap surgery after excision of the necrotic tissue, and also shortened the average recovery time.

Bioactive lipids-based therapeutic approach to COVID-19 and other similar infections

It is suggested that COVID-19 (coronavirus) and other enveloped viruses can be inactivated by bioactive lipids. Bioactive lipids (BALs) AA, gamma-linolenic acid (GLA), dihomo-GLA (DGLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) are precursors to anti-inflammatory metabolites prostaglandin E1, lipoxin A4, resolvins, protectins and maresins that enhance phagocytosis of macrophages and leukocytes to clear debris, enhance microbial clearance and wound healing to restore homeostasis. BALs influence cell membrane fluidity and thus, prevent SARS-CoV-2, influenza, and Arboviruses (such as Chikungunya, Dengue, Zika) to infect the target cells. BALs modulate the generation of M1 and M2 macrophages. Mesenchymal and adipose tissue-derived stem cells secrete LXA4 and other BALs to bring about their beneficial actions in COVID-19. Prostaglandin E2 (PGE2), derived from arachidonic acid, triggers generation of anti-inflammatory lipoxin A4 and thus, modulates pathogenesis of COVID-19. AA, the precursor to both PGE2 and LXA4, and thus, is suited to prevent and ameliorate COVID-19.