Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism / 中华医学杂志(英文版)

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.

Palbociclib induces cell cycle arrest and senescence of human renal tubular epithelial cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells.@*METHODS@#Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting.@*RESULTS@#Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 (@*CONCLUSIONS@#Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.

Blocking pannexin-1 alleviates cisplatin-induced acute kidney injury in mice by reducing renal inflammatory cell infiltration / 南方医科大学学报

OBJECTIVE@#To investigate the effect of blocking pannexin-1 against acute kidney injury induced by cisplatin.@*METHODS@#Twenty-six male C57BL/6 mice aged 6-8 weeks were randomly divided into control group, cisplatin model (Cis) group and cisplatin + carbenoxolone treatment group (Cis + CBX). In Cis group and Cis + CBX group, the mice were injected intraperitoneally with 20 mg/kg of cisplatin and with CBX (20 mg/kg) at 30 min before and 24 and 48 h after cisplatin inhjection, respectively. All the mice were sacrificed at 72 h after cisplatin injection, and plasma and kidney samples were collected for testing mRNA and protein expression levels of pannexin-1 in the renal tissue using RT-qPCR and Western blotting and for detecting plasma creatinine and BUN levels; the pathological changes in the renal tissues were observed using Periodic Acid-Schiff staining. The expression of kidney injury molecule 1 (KIM-1) was examined using immunohistochemistry and the mRNA expressions of KIM-1 and neutrophil gelatinase- related lipid transport protein (NGAL) were detected by RT-qPCR to evaluate the injuries of the renal tubules. The infiltration of F4/80-positive macrophages and CD4-positive T cells were observed by immunofluorescence. In the experiment, human proximal tubule epithelial cell line HK-2 was stimulated with 50 μmol/L cisplatin to establish a cell model of acute kidney injury, and the mRNA and protein expressions of pannexin-1 were detected by RT-qPCR and Western blotting at 4, 6, 12, 18 and 24 h after the stimulation.@*RESULTS@#Compared with the control mice, the cisplatin-treated mice showed significantly up-regulated protein levels ( < 0.05) and mRNA levels ( < 0.005) of pannexin-1 in the kidney tissue. Cisplatin stimulation also caused significant increases in the protein levels ( < 0.005) and mRNA levels ( < 0.005) of pannexin-1 in cultured HK-2 cells. Compared with cisplatin-treated mice, the mice treated with both cisplatin and the pannexin-1 inhibitor CBX showed obviously lessened kidney pathologies and milder renal tubular injuries with significantly reduced plasma BUN and Scr levels ( < 0.01), expressions of KIM-1 and NGAL in the kidney ( < 0.05), and infiltration of F4/80-positive macrophages ( < 0.01) and CD4- positive T cells ( < 0.05) in the kidney tissues.@*CONCLUSIONS@#In cisplatin induced acute kidney injury mice model, Pannexin-1 expression is up-regulated in the kidneys tissue, and blocking pannexin-1 alleviates the acute kidney injury reducing renal inflammatory cell infiltration.

The four processes of sensation,experience,acceptance and absorption in medical ethics education / 中华医学教育探索杂志

To adapt to the conversion from the traditional biological medical model to biological,psychological and social medicine model,we claim the four processes of sensation,experience,acceptance and absorption in medical ethics education,aiming to establish the harmonious relationship in medical treatment,and at the same time bear the task of developing themedical and health services of socialism.

The practice and discussion of"six processes"teaching methods in functional design experiments / 中华医学教育探索杂志

The functional experiment teaching is an inspection to students of their thinking methods and the operation abilities,and is also the summary and sublimation of this course theories teaching.To adapt to the demand for cultivation of the talented person by innovation education,we probe into the improvement of teaching methods of the functional design experiment,and practiced the new teaching system of "six processes"teaching methods such as speaking briefly,giving a demonstration,questioning,giving clue,study and discussion,evaluation,and push forward the biomedical science modes toward the development of "living creature-mental state-social medical science mode"direction.

The exploration and practice of the humanities education in the elective course for all-round development of the local medical college / 中华医学教育探索杂志

This text explored the practice of the humanities education in the elective course for all-round development of the local medical college. We will plan to establish the aspect to develop new"growth order" in this course, which contributes to the harmonious development of the medical studnts and cultivating the teachers’humanities accomplishment.

Interventional therapy of huge aneurysm / 介入放射学杂志

Objective To evaluate the methods and the efficacy of interventional therapy for huge aneurysm.Methods Seven patients with huge aneurysm including 2 with pulmonary aneurysm, 2 with renal aneurysm, 1 with humeral artery aneurysm, 1 with right common iliac artery aneurysm, 1 with right internal iliac artery aneurysm. Among these, 5 were true aneurysm, and 2 were pseudoaneurysms caused by congenital, trauma, arteriosclerosis. Three patients were treated with endovascular covered stent graft and 2 patients with embolization containing metallic coils. Two patients were treated with partial aneurysm and feeding artery trunk embolization with metallic coils. Results All 7 patients were successful carried out the interventional therapy with successful rate of 100%. Six aneurysms were completely obstructed with disappearance of symptoms and signs. One died of aneurysm rupture. No other complication occurred.Conclusion Interventional therapy for huge aneurysm is an effective method.