Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE −/−

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE−/− mice were randomized (n=10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c, IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/− mice as compared to the untreated mice (P<0.05, P<0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P<0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process

Risk factors of distant brain failure for patients with newly diagnosed brain metastases treated with stereotactic radiotherapy alone

<p>Abstract</p> <p>Objective</p> <p>To explore the risk factors of distant brain failure (DBF) for patients with brain metastasis (BM) who were treated with stereotactic radiotherapy alone and to group the patients on the basis of their risk levels.</p> <p>Methods and Materials</p> <p>We retrospectively analyzed 132 newly diagnosed BM patients who were treated with stereotactic radiotherapy alone from May 2000 to April 2010. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses.</p> <p>Results</p> <p>The 1-year incidence rate of DBF was 44.7%, and the median DBF time (MDBFT) was 18 months. In multivariate analysis, the risk factors of DBF were the number of BMs greater than 1 (p = 0.041), uncontrolled extracranial disease (p = 0.005), interval time (IT) of less than 60 months between the diagnosis of primary tumor and BM (p = 0.024), and total volume of BM was greater than 6 cc (p = 0.049). Each risk factor was assigned 1 score. The median survival times for the patients with scores of 0-1, 2-3, and 4 were 31, 12, and 10 months, respectively, and the corresponding MDBFTs were not reached, 13, and 3 months, respectively, (p < 0.001). The crude DBF incidence rates in patients with scores of 0-1, 2-3, and 4 were 14.8%, 50.0%, and 76.9%, respectively, (p < 0.001).</p> <p>Conclusions</p> <p>The patients with scores of 0-1 had a lower risk of DBF than the patients with higher scores did, and it may be reasonable to treat these patients with SRS alone and resort to whole-brain radiation therapy only for salvage. The patients with a score of 4 had the highest risk of developing DBF after stereotactic radiotherapy alone, these patients may be candidates for initial whole-brain radiation therapy or clinical trials. The patients with a score of 2-3 had a moderate risk of developing DBF, SRT alone combined with close clinical monitoring would be the optimal treatment regimen for such patients, and for those patients with difficulties in receiving close clinical mornitoring, SRT combined with WBRT will be more suitable.</p

New insights into the methods for predicting ground surface roughness in the age of digitalisation

Grinding is a multi-length scale material removal process that is widely employed to machine a wide variety of materials in almost every industrial sector. Surface roughness induced by a grinding operation can affect corrosion resistance, wear resistance, and contact stiffness of the ground components. Prediction of surface roughness is useful for describing the quality of ground surfaces, evaluate the efficiency of the grinding process and guide the feedback control of the grinding parameters in real-time to help reduce the cost of production. This paper reviews extant research and discusses advances in the realm of machining theory, experimental design and Artificial Intelligence related to ground surface roughness prediction. The advantages and disadvantages of various grinding methods, current challenges and evolving future trends considering Industry-4.0 ready new generation machine tools are also discussed

Antibody-Mediated LILRB2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells to Kill Mycobacterium tuberculosis

Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade of SHP1/2 phosphatase increased proinflammatory cytokine responses and phosphorylation of ERK1/2, p38 MAPK, and NF-kB in Mtb-infected MDSCs. LILRB2 antagonism also upregulated anti-mycobacterial iNOS gene expression and an increase in both nitric oxide and reactive oxygen species synthesis. Because genes associated with the anti-mycobacterial function of M1-MФs were enhanced in MDSCs following mab treatment, we propose that LILRB2 antagonism reprograms MDSCs from an immunosuppressive state towards a pro-inflammatory phenotype that kills Mtb. LILRB2 is therefore a novel therapeutic target for eradicating Mtb in MDSCs

Facile one-pot synthesis of three different substituted thiazoles from propargylic alcohols

Three different substituted thiazoles have been successfully synthesized from readily available propargylic alcohols. Various secondary propargylic alcohols or tertiary propargylic alcohols participated well in the reaction, providing the desired products in good yields. This method provides a flexible and rapid route to substituted thiazoles.National Natural Science Foundation of China [20772098]; Program for New Century Excellent Talents in Fujian Province Universit

FeCl3-Catalyzed Propargylation-Cycloisomerization Tandem Reaction: A Facile One-Pot Synthesis of Substituted Furans

An efficient FeCl3-catalyzed tandem propargylation-cycloisomerization reaction of propargylic alcohols or acetates with 1,3-dicarbonyl compounds, leading to the synthesis of substituted furans, has been developed.National Natural Science Foundation of China [20772098, 30572250]; Fujian Province Universit