Lactulose: an effective preventive and therapeutic option for ischemic stroke by production of hydrogen

Lactulose, a synthetic sugar not able to be digested and absorbed by human beings, is widely used to treat constipation and hepatic encephalopathy clinically. Through fermentation by the bacteria in the gastrointestinal tract, lactulose can produce considerable amount of hydrogen, which is protective for ischemic stroke as a unique antioxidant. We propose that lactulose can induce the production of endogenous hydrogen that in turn reduces oxidative stress and ameliorate the stroke damage in human beings

All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation

Background. All-trans-retinoic acid (atRA) is effective for many proliferative diseases. We investigated the protective effects of atRA against atherosclerosis. Methods. Rabbits were randomly allocated to receive basal diet or an HFD for 4 weeks. HFD group then received rosuvastatin (3 mg/day), atRA (5 mg/kg/day), or the same volume of vehicle, respectively, for next 8 weeks. Results. HFD group showed increases in plasma lipids and aortic plaque formation. P-selectin expression and fibrinogen binding on platelets or deposition on the intima of the aorta also increased significantly as did the levels of TNF-α, IL-6, and fibrinogen in plasma. After 8 weeks of treatment with atRA, there was a significant decrease in plasma lipids and improvement in aortic lesions. AtRA also inhibited the expression of P-selectin and fibrinogen binding on platelets and deposition on the intima of the aorta. Conclusion. AtRA can ameliorate HFD-induced AS in rabbits by inhibiting platelet activation and inflammation

Novel link between E2F1 and Smac/DIABLO: proapoptotic Smac/DIABLO is transcriptionally upregulated by E2F1

Deregulated expression of E2F1 not only promotes S-phase entry but also induces apoptosis. Although it has been well documented that E2F1 is able to induce p53-dependent apoptosis via raising ARF activity, the mechanism by which E2F induces p53-independent apoptosis remains unclear. Here we report that E2F1 can directly bind to and activate the promoter of Smac/DIABLO, a mitochondrial proapoptotic gene, through the E2F1-binding sites BS2 (−542 ∼ −535 bp) and BS3 (−200 ∼ −193 bp). BS2 and BS3 appear to be utilized in combination rather than singly by E2F1 in activation of Smac/DIABLO. Activation of BS2 and BS3 are E2F1-specific, since neither E2F2 nor E2F3 is able to activate BS2 or BS3. Using the H1299 ER-E2F1 cell line where E2F1 activity can be conditionally induced, E2F1 has been shown to upregulate the Smac/DIABLO expression at both mRNA and protein levels upon 4-hydroxytamoxifen treatment, resulting in an enhanced mitochondria-mediated apoptosis. Reversely, reducing the Smac/DIABLO expression by RNA interference significantly diminishes apoptosis induced by E2F1. These results may suggest a novel mechanism by which E2F1 promotes p53-independent apoptosis through directly regulating its downstream mitochondrial apoptosis-inducing factors, such as Smac/DIABLO

Increased CD14+HLA-DR−/low Myeloid-Derived Suppressor Cells Correlate With Disease Severity in Systemic Lupus Erythematosus Patients in an iNOS-Dependent Manner

Myeloid-derived suppressor cells (MDSCs) comprise of a population of cells, which suppress the innate and adaptive immune system via different mechanisms. MDSCs are accumulated under pathological conditions. The present study aimed to clarify the pathological role of MDSCs in systemic lupus erythematosus (SLE) patients. Consequently, the level of circulating M-MDSCs was significantly increased in newly diagnosed SLE patients as compared to healthy controls. An elevated level of M-MDSCs was positively correlated with the disease severity in SLE patients and an immunosuppressive role was exerted in an iNOS-dependent manner. The decrease in the number of M-MDSCs after therapy rendered them as an indicator for the efficacy of treatment. These results demonstrated that M-MDSCs participated in the pathological progress in SLE patients. Thus, MDSCs are attractive biomarkers and therapeutic targets for SLE patients

The role of Raptor in lymphocytes differentiation and function

Raptor, a key component of mTORC1, is required for recruiting substrates to mTORC1 and contributing to its subcellular localization. Raptor has a highly conserved N-terminus domain and seven WD40 repeats, which interact with mTOR and other mTORC1-related proteins. mTORC1 participates in various cellular events and mediates differentiation and metabolism. Directly or indirectly, many factors mediate the differentiation and function of lymphocytes that is essential for immunity. In this review, we summarize the role of Raptor in lymphocytes differentiation and function, whereby Raptor mediates the secretion of cytokines to induce early lymphocyte metabolism, development, proliferation and migration. Additionally, Raptor regulates the function of lymphocytes by regulating their steady-state maintenance and activation