Objective: To study the serum interleukin-37 (IL-37) level changes in patients with acute coronary syndrome (ACS) and to explore the relationship between IL-37 and coronary atherosclerotic plaque.
Methods: Our research included 3 groups. ACS group, n=60, SAP (stable angina pectoris) group, n=30 and Control group, the subjects with normal coronary artery, n=15. The peripheral serum levels of IL-37 were examined by ELISA and the differences were compared among different groups.
Results: ① The serum levels of IL-37 at admission were as ACS group < SAP group < Control group, P<0.05.②Intervention could transitionally decrease IL-37 level in SAP group. With 4 weeks treatment, IL-37 levels were signiifcantly increased in both ACS group and SAP group than admission time, while they were still lower than Control group, P<0.05.③The serum level of IL-37 at admission was negatively related to IL-18 (r=-0.79, P<0.05), the ratio of IL-18/IL-37 were as ACS group>SAP group>Control group, P<0.05.④In ACS group, IL-37 level was negatively related to GRACE score (r=-0.71, P<0.05), the ratio of IL-18/IL-37 was positively related to GRACE score (r=0.73, P<0.05).⑤The diagnosis of ACS could be basically excluded if the patients with IL-37>77ug/L.
Conclusion: The serum IL-37 might be involved in the inlfammatory process in ACS patients, it could be expected as an index for ACS monitor and evaluation in clinical practice.

Human induced pluripotent stem cells (hiPSCs) are promising in regenerative medicine. However, the pluripotent stem cells (PSCs) may form clumps of cancerous tissue, which is a major safety concern in PSCs therapies. Rapamycin is a safe and widely used immunosuppressive pharmaceutical that acts through heterodimerization of the FKBP12 and FRB fragment. Here, we aimed to insert a rapamycin inducible caspase 9 (riC9) gene in a safe harbor AAVS1 site to safeguard hiPSCs therapy by drug induced homodimerization. The donor vector containing an EF1α promoter, a FRB-FKBP-Caspase 9 (CARD domain) fusion protein and a puromycin resistant gene was constructed and co-transfected with sgRNA/Cas9 vector into hiPSCs. After one to two weeks screening with puromycin, single clones were collected for genotype and phenotype analysis. Finally, rapamycin was used to induce the homodimerization of caspase 9 to activate the apoptosis of the engineered cells. After transfection of hiPSCs followed by puromycin screening, five cell clones were collected. Genome amplification and sequencing showed that the donor DNA has been precisely knocked out at the endogenous AAVS1 site. The engineered hiPSCs showed normal pluripotency and proliferative capacity. Rapamycin induced caspase 9 activation, which led to the apoptosis of all engineered hiPSCs and its differentiated cells with different sensitivity to drugs. In conclusion, we generated a rapamycin-controllable hiPSCs survival by homodimerization of caspase 9 to turn on cell apoptosis. It provides a new strategy to guarantee the safety of the hiPSCs therapy.
Humans ; Induced Pluripotent Stem Cells ; Sirolimus/metabolism* ; Caspase 9/metabolism* ; RNA, Guide, CRISPR-Cas Systems ; Pluripotent Stem Cells/metabolism* ; Cell Differentiation ; Puromycin/metabolism*

[Abstract] Objective: To study the effects of ursolic acid cooperated with gemcitabine on proliferation and apoptosis of pancreatic cancer PANC-1 cells. Methods: Human pancreatic cancer cell line PANC-1 was cultured in vitro with ursolic acid and gemcitabine respectively; and MTT assay was used to determine the IC50 of ursolic acid and gemcitabine, thus obtaining the best drug concentration. Ursolic acid (2 µmol/L) and gemcitabine (0.2 µmol/L) alone or in combination was used to treat PANC-1 cells; trypan blue assay was used to test cell viability, and PI staining was used to examine the cell apoptosis; wound healing was used to detect the proliferation and migration of PANC-1 cells. The protein expressions of P-JNK, Bcl-2, IL-6, P-Stat 3, NF-κB and Cox-2 in cells of each treatment group were detected using Western blotting. Results: Both ursolic acid and gemcitabine could significantly inhibit the proliferation of PANC-1 cells, and the IC50 is 13.67 and 2.78 µmol/L, respectively; and the final concentrations were determined at 2 and 0.2 µmol/L for ursolic acid and gemcitabine, respectively. Compared with single drug treatment, the combined treatment exerted a more prominent cell proliferation inhibition effect ([46.47±5.07]% vs [78.38±8.65]%, [76.12±3.23]%, all P<0.05), apoptosis-induction effect ([39.78± 7.01]% vs [20.35±8.51]%, [20.35±8.51]%, all P<0.01) and migration inhibition effect (P<0.01) on PANC-1 cells. Western blotting showed that the combined treatment strongly inhibited Bcl-2 and IL-6 expression, accelerated P-JNK protein expression compared with single drug treatment. Conclusion: The synergistic effect of ursolic acid and gemcitabine enhanced the inhibition on proliferation, migration, and promoted cell apoptosis of human pancreatic cancer cell line PANC-1, the mechanism may be associated with inhibition of Bcl-2, Il-6, P-stat 3 proteins and promotion of P-JNK protein.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*