ABSTRACT
BACKGROUND AND OBJECTIVE@#Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.@*METHODS@#Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively.@*RESULTS@#A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition.@*CONCLUSIONS@#In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Subject(s)
Animals , Male , Mice , Dexamethasone/therapeutic use , Disease Models, Animal , Kupffer Cells/physiology , Liver Failure, Acute/pathology , Mice, Inbred C57BL , Nuclear Receptor Subfamily 4, Group A, Member 1/physiology , Receptors, Glucocorticoid/physiologyABSTRACT
OBJECTIVE: To systematically review the safety and effectiveness of indocyanine green(ICG) fluorescence imaging for precise diagnosis and treatment of liver neoplasms.METHODS: PubMed,EMbase,The Cochrane Library,CNKI,WanFang Data and VIP databases were electronically searched to collect cohort Studies which involved ICG fluorescence imaging for precise diagnosis and treatment of liver neoplasms. The retrieval time was from inception of the database to June 2019. Screened the literatures,extracted data,and Meta-analysis was performed by using RevMan 5.3 software.RESULTS: 10 studies were finally included involving 803 patients,with 328 cases in ICG molecular fluorescence imaging group and 475 patients in the control group. The results of meta-analysis showed that in ICG fluorescence imaging group,compared with the control group,the blood transfusion rate was decreased(OR=0.42,95%CI0.22～0.80,P=0.008),the rate of negative incision margin was increased(OR=3.22,95%CI 1.09～9.51,P=0.03),the incidence of postoperative complications was decreased(OR=0.49,95%CI 0.28～0.85,P=0.01). However,there was no statistical differences between the two groups in terms of perioperative blood loss,operation time or hospitalization time(all P>0.05).CONCLUSION: The application of ICG fluorescence imaging in precise diagnosis and treatment of liver neoplasms can effectively reduce the incidence of blood transfusion,the incidence of postoperative complications,and increase the rate of negative incision margin.
ABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs.</p><p><b>METHODS</b>Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 μg/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor.</p><p><b>RESULTS</b>After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 ± 0.3)% vs. (33.9 ± 2.7)%, P = 0.009]. After the treatment with 1 μg/mL and 10 μg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 ± 10.0)% (P = 0.012) and (52.9 ± 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 ± 3.3)% (P = 0.434) and (26.5 ± 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 ± 5.3)% to (60.6 ± 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 ± 0.2)% to (28.3 ± 0.6)% (P = 0.013).</p><p><b>CONCLUSIONS</b>Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU.</p>