Natural Products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy

In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions.Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world.In recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients.Natural products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer drugs.And numerous NPs have been reported to act on cancer energy metabolism targets.Herein,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Nomogram to predict postoperative complications in elderly with total hip replacement

BACKGROUND By analyzing the risk factors of postoperative complications in elderly patients with hip replacement,We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients.AIM To develop a nomogram model for risk stratification of postoperative complications in elderly with total hip replacement patients.METHODS A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1,2017 to August 31,2019 were included into this study.Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients.A nomogram was developed by R software and validated to predict the risk of postoperative complications.RESULTS Multivariate logistic regression analysis revealed that age(OR=1.05,95%CI:1.00-1.09),renal failure(OR=0.90,95%CI:0.83-0.97),Type 2 diabetes(OR=1.05,95%CI:1.00-1.09),albumin(ALB)(OR=0.91,95%CI:0.83-0.99)were independent risk factors of postoperative complication in elderly patients with hip replacement(P<0.05).For validation of the nomogram,receive operating characteristic curve revealed that the model predicting postoperative complication in elderly patients with hipreplacement was the area under the curve of 0.8254 (95%CI: 0.78-0.87), the slope of the calibrationplot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (χ^(2) = 10.16, P =0.4264), calibration in R E_(max) = 0.176, E_(avg) = 0.027, which all demonstrated that the model was ofgood accuracy.CONCLUSIONThe nomogram predicting postoperative complications in patients with total hip replacementconstructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination andaccuracy, which was of clinical significance.

Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway

OBJECTIVE： To investigate the tumor inhibition effect of Yangfei Kongliu Formula （YKF）, a compound Chinese herbal medicine, combined with cisplatin （DDP） and its action mechanisms. METHODS： C57BL/6 mice with Lewis lung carcinoma were divided into six groups： control group （C）, DDP group （2 mg/kg, DDP）, low-dose YKF group （2.43 g/kg, L）, high-dose YKF group （24.3 g/kg, H）, low- dose YKF combined with DDP group （L ＋ DDP） and high-dose YKF combined with DDP group （H ＋ DDP）. Transforming growth factor-β1 （TGF-β1）, mothers against decapentaplegic homolog 3 （Smad3） and Smad7 levels were measured with quantitative real-time polymerase chain reaction （qPCR）, Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 （IL-2） and tumor necrosis factor-α （TNF-α）. RESULTS： YKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups （P 〈 0.05）. There was no significant difference between high-dose YKF group and low-dose YKF group （P 〉 0.05）. We also found that the expression levels of TGF-β1 and Smad3 were both significantly decreased by YKF relative to the control group （P 〈 0.05）. Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-β1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group （P 〈 0.05）. Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition （P 〈 0.05）, showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group （P 〈 0.05）. Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-β1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group （P 〈 0.05）. CONCLUSION： YKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-β1 signaling pathway.