The effect of combination therapy of allicin and fenofibrate on high fat diet-induced vascular endothelium dysfunction and liver damage in rats

<p>Abstract</p> <p>Background</p> <p>It is designed to investigate the effects of combination therapy of allicin and fenofibrate on the endothelial and liver functions in rats with hyperlipidemia.</p> <p>Methods</p> <p>The healthy male Wistar rats fed high fat diet were treated with fenofibrate (80 mg/kg per day) alone, allicin (60 mg/kg per day) alone and a lower dasage of combined therapy (allicin 20 mg/kg per day and fenofibrate 30 mg/kg per day) respectively for 8 weeks. The serum levels of cholesterol, triglyceride, nitrogen oxidative, alanine transferase (ALT) and aspartate transferase (AST) were determined. Acetylcholine-induced endothelium-dependent vascular relaxation (EDVR) of aorta rings was tested, and the morphologic changes of liver tissue were observed.</p> <p>Results</p> <p>Compared with high fat diet control, fenofibrate alone or the combined therapy increased remarkably the levels of high density lipoprotein respectively (P < 0.05). Both single and combined therapy of fenofibrate and allicin significantly enhanced the levels of NO (P < 0.01 or P < 0.05), but the combined therapy had greatest high EDVR responses (P < 0.01). Furthermore, the reduced levels of ALT and AST were significantly obvious in the combined therapy groups (P < 0.01 or P < 0.05). In addition, the lower dosage of combined therapy significantly ameliorated severe fatty degeneration of liver cells occurred in the high fat diet fed rat although the single fenofibrate treatment showed spotty necrosis of liver cells and bile duct expansion.</p> <p>Conclusion</p> <p>Combination therapy with allicin and fenofibrate can effectively enhance the protective effects on endothelial function and reduce the hepatic damage in rats with hyperlipidemia.</p

Serum Metabolomic Signatures of Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma

Lymph node metastasis was recently proven to be the single most important prognostic factor for esophageal cancer, an important malignant tumor with poor prognosis. A global metabolomics approach was applied to study lymph node metastasis of esophageal squamous cell carcinoma (ESCC). Metabolomics analyses were performed using gas chromatography/mass spectrometry together with univariate and multivariate statistical analyses. There were clear metabolic distinctions between ESCC patients and healthy subjects. ESCC patients could be well-classified according to lymph node metastasis. We further identified a series of differential serum metabolites for ESCC and lymph node metastatic ESCC patients, suggesting metabolic dysfunction in proliferation (aerobic glycolysis, glutaminolysis, fatty acid metabolism, and branched-chain amino acid consumption), apoptosis, migration, immune escape, and oxidative stress of cancer cells in metastatic ESCC patients. In total, three serum metabolites (valine, γ-aminobutyric acid, and pyrrole-2-carboxylic acid) were selected by binary logistic regression analysis, and their combined use resulted in high diagnostic capacity for ESCC metastasis by receiver operating characteristic analysis. The present metabolomics study staged ESCC patients by lymph node metastasis, and the results suggest promising applications of this approach in prognostic prediction, tailored therapeutics, and understanding the pathological mechanisms of poor prognosis of ESCC patients

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181&ndash;0.619, p &lt; 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554&ndash;1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future