Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.

AIM: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. METHODS: ESI-QTRAP-MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. RESULTS: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition-mediated tubule injury recovery. Reactive oxygen species/NF-κB signaling activation played a vital role in fumarate-mediated tubule injury. CONCLUSION: Our studies demonstrated that the mitochondrial-derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate-mediated ROS/NF-κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.

[Ganoderma lucidum polysaccharides promote T lymphocyte infiltration into tumor by regulating expression of ICAM-1 in endothelial cells].

Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 µg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.

Tegafur deteriorates established cardiovascular atherosclerosis in colon cancer: A case report and review of the literature.

BACKGROUND: Cardiac toxic effect of tegafur (S-1) is extremely rare, and there has been no report on this issue so far. CASE SUMMARY: We herein report a typical case of single S-1 administration after radical operation for colon cancer. The patient had no background or medical history of acute coronary syndrome (ACS), and only aortic and coronary atherosclerosis was revealed by computed tomography (CT) before surgery. He complained of sternum pain during the fifth cycle of S-1 treatment. Electrocardiogram (ECG) and serum cardiac marker cardiac troponin T (cTnT) strongly suggested ACS, which was possibly caused by S-1 cardiotoxicity. CONCLUSION: Monitoring protocols based on ECG, CT, and cTnT should be performed in real time to evaluate cardiac function during S-1 administration.

Possible connection between elevated serum α-fetoprotein and placental necrosis during pregnancy: A case report and review of literature.

Placenta previa is the main cause of bleeding throughout pregnancy, and it is associated with serious complications, such as infection, that lead to a poor prognosis. Gynecological sonography is recommended as the first-line examination technique for the surveillance and determination of vaginal bleeding and for early intervention. We report the case of a patient with gradually expanded hypoechoic lesion and extremely high serum α-fetoprotein level during her third trimester, and discuss their potential relationship in evaluating the progression of placental necrosis.

Identification, quantification and antioxidant activity of acylated flavonol glycosides from sea buckthorn (Hippophae rhamnoides ssp. sinensis).

A novel acylated flavonol glycoside: isorhamnetin (3-O-[(6-O-E-sinapoyl)-ß-D-glucopyranosyl-(1→2)]-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside) (1), together with two known acylated flavonol glycosides: quercetin (3-O-[(6-O-E-sinapoyl)-ß-D-glucopyranosyl-(1→2)]-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside) (2) and kaempferol (3-O-[(6-O-E-sinapoyl)-ß-D-glucopyranosyl-(1→2)]-ß-D-glucopyranosyl-7-O-α-L-rhamnopyranoside) (3) were isolated from the n-butanol fraction of sea buckthorn (Hippophae rhamnoides ssp. sinensis) berries for the first time by chromatographic methods, and their structures were elucidated using UV, MS, (1)H and (13)C NMR, and 2D NMR. Compounds 1-3 showed good scavenging activities, with respective IC50 values of 8.91, 4.26 and 30.90 µM toward the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical; respective Trolox equivalent antioxidant capacities of 2.89, 4.04 and 2.44 µM µM(-1) toward 2,2'-azino-bis-3-ethyl-benzothiazoline-6-sulphonate (ABTS) radical. The quantitative analysis of the isolated acylated flavonol glycosides was performed by HPLC-DAD method. The contents of compounds 1-3 were in the range of 12.2-31.4, 4.0-25.3, 7.5-59.7 mg/100 g dried berries and 9.1-34.5, 75.1-182.1, 29.2-113.4 mg/100 g dried leaves, respectively.

[Effects of Armillariella tabescens polysaccharide IPS-B2 on activity of mouse peritoneal macrophages and transcription of related gene].

OBJECTIVE: To observe the effect of IPS-B2 on mouse peritoneal macrophages and the transcription of IL-1beta, IL-6, TNF-alpha and iNOS. METHOD: ELISA method and Griess method were used to detect the effect of mouse peritoneal macrophages produce cytokines IL-1beta, IL-6, TNF-alpha and cytotoxic effectors NO. The transcription of IL-1beta, IL-6, TNF-alpha and iNOS was detected by real-time RT-PCR method. RESULT: IPS-B2 could not promote mouse peritoneal macrophage production, but it could significantly improve the IL-1beta, IL-6, TNF-alpha content in mouse peritoneal macrophages culture supernatant, and increase the gene expression of IL-1beta, IL-6, TNF-alpha and iNOS. CONCLUSION: IPS-B2 can enhance the ability of peritoneal macrophages to excrete bioactive substances and promote the transcription of bioactive substances to antitumor.

[Research on Sailong boneextracts on proliferation and apoptosis of osteoblast cells].

OBJECTIVE: To investigate the metabolic regulation and apoptosis of Sailong bone extracts on rat osteoblast cells in vitro. METHOD: Sailong bone fat-soluble extract, Sailong bone ethanol extract and Sailong bone aqueous extract were extracted with super critical fluid extraction (SCFE) , and Sailong bone boiling water component was extracted with distilled water directly. MTT assay was applied to determine the proliferation of the cell promoted by four Sailong bone extracts and PAS assay for the aqueous proportion of the cell at different doses. RESULT: Sailong bone fat-soluble and aqueous extract (each 10 mg x mL (-1)) could significantly improve the proliferation of rat osteoblast cells ROS 17/2. 8 (P < 0. 01). Compared with the blank, the proportion of xub-G, of the different extracts from Sailong bone is reduce evidently. The result have shown the extracts from Sailong bone could reduce the rate of aqueous of cell and could suspend the aqueous. CONCLUSION: Sailong bone can promoting the proliferation, degrading the rate of the apoptosis and delay the development of osteoblast to be the substitute of the bone of tiger as a Chinese materia medica.

[Effect of Spatholobus suberectus on the bone marrow cells and related cytokines of mice].

OBJECTIVE: To study the effect of Spatholobus suberectus on proliferation and the hematonic mechanism. METHOD: The techniques of culture of hematopoietic cell and hematopoietic growth factor (HGF) assay were used. RESULT: Spatholobus suberectus could obviously promote the proliferation of bone marrow cells in healthy and anaemic mice. The culture media of spleen cell, macrophage, lung and skeletal muscle treated with S. suberectus had much stronger stimulating effects on hematopoietic cells. CONCLUSION: S. suberectus may enhance hematopoiesis by directly or indirectly stimulating stroma cell in hematopoietic inductive microenvironment and muscle tissue to secrete some HGF (Epo, GM-CSF, IL, and MK-CSF). This is one of the biological mechanisms for hematonic effect of S. suberectus.