LL-37 improves sepsis-induced acute lung injury by suppressing pyroptosis in alveolar epithelial cells.

BACKGROUND: LL-37 (also known as murine CRAMP) is a human antimicrobial peptide that plays a crucial role in innate immune defence against sepsis through various mechanisms. However, its involvement in sepsis-induced lung injury remains unclear. OBJECTIVES: This work investigates the impact of LL-37 on pyroptosis generated by LPS in alveolar epithelial cells. The research utilizes both in vivo and in vitro sepsis-associated acute lung injury (ALI) models to understand the underlying molecular pathways. METHODS: In vivo, an acute lung injury model induced by sepsis was established by intratracheal administration of LPS in C57BL/6J mice, which were subsequently treated with low-dose CRAMP (recombinant murine cathelicidin, 2.5 mg.kg-1) and high-dose CRAMP (5.0 mg.kg-1). In vitro, pyroptosis was induced in a human alveolar epithelial cell line (A549) by stimulation with LPS and ATP. Treatment was carried out with recombinant human LL-37, or LL-37 was knocked out in A549 cells using small interfering RNA (siRNA). Subsequently, haematoxylin and eosin staining was performed to observe the histopathological changes in lung tissues in the control group and sepsis-induced lung injury group. TUNEL and PI staining were used to observe DNA fragmentation and pyroptosis in mouse lung tissues and cells in the different groups. An lactate dehydrogenase (LDH) assay was performed to measure the cell death rate. The expression levels of NLRP3, caspase1, caspase 1 p20, GSDMD, NT-GSDMD, and CRAMP were detected in mice and cells using Western blotting, qPCR, and immunohistochemistry. ELISA was used to assess the levels of interleukin (IL)-1ß and IL-18 in mouse serum, bronchoalveolar lavage fluid (BALF) and lung tissue and cell culture supernatants. RESULTS: The expression of NLRP3, caspase1 p20, NT-GSDMD, IL 18 and IL1ß in the lung tissue of mice with septic lung injury was increased, which indicated activation of the canonical pyroptosis pathway and coincided with an increase in CRAMP expression. Treatment with recombinant CRAMP improved pyroptosis in mice with lung injury. In vitro, treatment with LPS and ATP upregulated these classic pyroptosis molecules, LL-37 knockdown exacerbated pyroptosis, and recombinant human LL-37 treatment alleviated pyroptosis in alveolar epithelial cells. CONCLUSION: These findings indicate that LL-37 protects against septic lung injury by modulating the expression of classic pyroptotic pathway components, including NLRP3, caspase1, and GSDMD and downstream inflammatory factors in alveolar epithelial cells.

Protection of Exogenous Phosphocreatine for Myocardium in Percutaneous Coronary Intervention Related to Inflammation.

OBJECTIVES: Although injury of myocardium after percutaneous coronary intervention (PCI) has been reported, the mechanism and effect of exogenous phosphocreatine (PCr) supplementation on the injury are yet to be elucidated. Biomarkers, such as interleukin-6 (IL-6) and variations in white blood cells for inflammation, and serum cardiac troponin I (cTnI) for myocardial injury are examined. METHODS: A total of 105 patients undergoing PCI were included and randomly divided into two groups: control (treated with routine hydration therapy) and PCr (treated with additional intravenous infusion of exogenous PCr). The serum levels of biomarkers were detected at administration and 4, 12, 24, and 48 h after PCI, with natural logarithmic (loge) transformation of data when modeling assumptions were not fulfilled. RESULTS: The level of loge-transformed IL-6 increased in both groups, especially at 12 and 24 h after the operation, and that of PCr group was less than the control group at 48 h. The content of loge-transformed cTnI was significantly increased in both groups, while that of the PCr group was markedly lower than the control group at all time points after PCI. Moreover, the ratio of neutrophils was elevated at all time points after PCI, while that of the PCr group was lower at 48 h, and the variations in the ratio of lymphocytes showed opposite results. CONCLUSIONS: Exogenous phosphocreatine reduces stent implantation, triggers inflammation manifested as decreased serum levels of IL-6 and the aggregation of neutrophils, and protects the myocardium of the patients undergoing PCI. These findings provided the potential mechanism and treatment for myocardial injury associated with PCI.

Effects of ramipril on serum monocyte chemoattractant protein 1, interleukin-18, and interleukin-10 in elderly patients with acute coronary syndrome.

Acute coronary syndrome (ACS) is a clinical syndrome caused by acute myocardial ischemia and a severe stage of coronary atherosclerosis heart disease. The aim of this study was to clarify whether ramipril was a therapeutic agent against monocyte chemoattractant protein 1 (MCP-1), interleukin 18 (IL-18), and interleukin 10 (IL-10) in elderly patients with ACS. A total of 190 subjects including 72 elderly patients with ACS (78.1% male, mean age 67.12 +/- 5.06 years), 60 elderly patients with stable angina pectoris (76.9% male, mean age 68.00 +/- 4.52 years), and 58 healthy volunteers (77.8% male, mean age 65.96 +/- 4.18 years) were recruited into the study. Serum MCP-1, IL-10, and IL-18 were determined in 132 elderly patients by enzyme-linked immunosorbent assay (ELISA) before and after treatment with low doses of ramipril (2.5-5 mg/day), and were determined in 58 healthy volunteers. The levels of serum MCP-1 and IL-18 were much higher in elderly patients with ACS than those in elderly patients with SAP and healthy volunteers. After treating with ramipril, the levels of MCP-1 and IL-18 were decreased in elderly patients with ACS. Moreover, ramipril significantly increased serum IL-10 in elderly patients with ACS. Ramipril plays an important role in elderly patients with ACS. With decreasing MCP-1 and IL-18, it can ameliorate cytokine-associated cardiac damage. This study may provide a new recognition of angiotensin-converting enzyme inhibitor for the treatment of ACS.

Cellulose derivatives carrying triphenylamine (TPA) moieties: synthesis and electro-optical properties.

A novel ethyl cellulose derivative [poly(1)] that carries triphenylamine moieties is synthesized with a moderate number-average molecular weight up to 78,200 in 85% yield by the reaction of 4-(diphenylamino)benzoic acid with the residual hydroxy group of ethyl cellulose. Poly(1) is soluble in common organic solvents including toluene, CHCl3, CH2Cl2, and tetrahydrofuran while insoluble in hexane, diethyl ether, and methanol. The polymer emits blue-green fluorescence with quantum yields up to 65% in CHCl3 and displays unique solvatochromism. The cyclic voltammograms of poly(1) indicate that the polymer carrying TPA moieties is electrochemically redox active. The onset temperature of weight loss of the poly(1) is about 177 degrees C according to thermogravimetric analysis in air.

[Characterization of pyrolysis of waste printed circuit boards by high-resolution pyrolysis gas chromatography-mass spectrometry].

Thermal degradation of pyrolysis of waste circuit boards was investigated by high-resolution pyrolysis gas chromatography-mass spectrometry (PyGC-MS) and thermogravimetry (TG). In helium atmosphere, the products of FR-4 waste printed circuit board were pyrolyzed at 350, 450, 550, 650, and 750 degrees degrees C, separately, and the pyrolysis products were identified by online MS. The results indicated that the pyrolysis products of the FR-4 waste circuit board were three kinds of substances, such as the low boiling point products, phenol, bisphenol and their related products. Moreover, under 300 degrees degrees C, only observed less pyrolysis products. As the increase of pyrolysis temperature, the relative content of the low boiling point products increased. In the range of 450-650 degrees degrees C, the qualitative analysis and character were similar, and the relative contents of phenol and bisphenol were higher. The influence of pyrolysis temperature on pyrolyzate yields was studied. On the basis of the pyrolyzate profile and the dependence of pyrolyzate yields on pyrolysis temperature, the thermal degradation mechanism of brominated epoxy resin was proposed.