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Cancer, characterized by uncontrolled tumor cells growth, is a highly fatal disease worldwide. Molecular simplification of natural compounds is a modern and less costly strategy in drug discovery. Mono-carbonyl analogs of curcumin (MACs) are curcumin-originated anticancer agents possessing potent bioactivity in vitro. In this work, the cytotoxicity of methoxyl-substituted MACs toward HepG2 cells was evaluated by MTT assay. Among these, 2,2′-methoxyl MAC exhibited the most potent anti-proliferation activity, and it could promote the ROS production, redox imbalance, lipid peroxidation, the loss of mitochondrial membrane potential, and ultimately lead to cell cycle arrest and apoptosis of HepG2 cells. These results suggest that enhancing ROS generation may be a potent strategy for the expansion of new anti-hepatocellular carcinoma agents. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to observe the effects of the overexpression of miR-3074-5p in human trophoblast cells in vitro. Design: Experimental in vitro study in HTR8/SVneo cells. Methods: HTR8/SVneo cells were transfected with miR-3074-5p mimic. The cell apoptosis and invasion were measured via flow cytometry and transwell assay, respectively. The expression levels of P53, Cyclin Dependent Kinase Inhibitor 1B (P27), BCL-2, BCL2 associated X (BAX), and BCL2 like 14 (BCL-G) in HTR8/SVneo cells were determined by Western blot. The alterations in gene expression profile of HTR8/SVneo cells were evaluated by complementary DNA microarray assay, and the differential expressions of dihydrolipoamide S-succinyltransferase (DLST), growth-associated protein 43 (GAP43), runt-related transcription factor 2 (RUNX2), and C-C type chemokine receptor 3 (CCR3) were validated by Western blot. Biofunctions of these differentially expressed genes were enriched by Gene Ontology analysis. Results: The overexpression of miR-3074-5p in HTR8/SVneo cells promoted cell apoptosis but inhibited cell invasion, being accompanied by the significantly elevated expressions of P27, BCL-2, and BCL-G. Meanwhile, an increased expression of P27 and P57 was also detected in a small sample size of placental villi of recurrent miscarriage (RM) patients. Totally, 411 genes and 397 genes were screened out, respectively, to be downregulated or upregulated at least by 2-folds in miR-3074-5p overexpressed HTR8/SVneo cells. These differentially expressed genes were involved in several important functions related to pregnancy. Subsequently, the reduced expressions of DLST and GAP43 proteins, as well as the increased expressions of CCR3 and RUNX2 proteins, were validated in miR-3074-5p overexpressed HTR8/SVneo cells. Conclusion: These data suggested a potential contribution of miR-3074-5p in the pathogenesis of RM by disturbing the normal activities of trophoblast cells. [ABSTRACT FROM AUTHOR]

Acute inflammation plays an important role in brain damage following cerebral ischemia and reperfusion (I/R) injury. The present study employed a rat model of middle cerebral artery occlusion to explore the neuroprotective effects of tanshinone IIA (TSN), which is widely used in China for treating cerebrovascular and cardiovascular diseases. Rats were divided into a sham-operated group and I/R transiently occluded then reperfused groups. Some of the I/R animals were treated daily for 7 or 15 days with two different doses of TSN. After 15 days, triphenyl tetrazolium chloride staining revealed less unstained area indicating fewer lesions in the TSN-treated I/R group relative to the untreated corresponding I/R group. TSN treatment dramatically reduced infarct sizes and reduced content of high mobility group box 1 protein following I/R. Nuclear translocation of NFκB was also attenuated in I/R animals subsequently receiving TSN. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining revealed more apoptosis in the I/R model group and this was reduced in the I/R animals treated with TSN for 15 days. Thus, TSN mitigates the severity of damage effected by I/R. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) results in neuronal apoptosis, autophagic cell death and necroptosis. Necroptosis is a newly discovered caspases-independent programmed necrosis pathway which can be triggered by activation of death receptor. Previous works identified that necrostatin-1 (NEC-1), a specific necroptosis inhibitor, could reduce tissue damage and functional impairment through inhibiting of necroptosis process following TBI. However, the role of NEC-1 on apoptosis and autophagy after TBI is still not very clear. In this study, the amount of TBI-induced neural cell deaths were counted by PI labeling method as previously described. The expression of autophagic pathway associated proteins (Beclin-1, LC3-II, and P62) and apoptotic pathway associated proteins (Bcl-2 and caspase-3) were also respectively assessed by immunoblotting. The data showed that mice pretreated with NEC-1 reduced the amount of PI-positive cells from 12 to 48 h after TBI. Immunoblotting results showed that NEC-1 suppressed TBI-induced Beclin-1 and LC3-II activation which maintained p62 at high level. NEC-1 pretreatment also reversed TBI-induced Bcl-2 expression and caspase-3 activation, as well as the ratio of Beclin-1/Bcl-2. Both 3-MA and NEC-1 suppressed TBI-induced caspase-3 activation and LC3-II formation, Z-VAD only inhibited caspase-3 activation but increased LC3-II expression at 24 h post-TBI. All these results revealed that multiple cell death pathways participated in the development of TBI, and NEC-1 inhibited apoptosis and autophagy simultaneously. These coactions may further explain how can NEC-1 reduce TBI-induced tissue damage and functional deficits and reflect the interrelationship among necrosis, apoptosis and autophagy. [ABSTRACT FROM AUTHOR]