Identification and analysis of anti-tumor effective substances in Yangzheng Mixture.

Yangzheng Mixture is a traditional Chinese medicine used in clinical practice as an adjuvant therapy for tumors. However, little is known about its active components in tumor treatment. The purpose of this study was to explore the potential anti-tumor components of Yangzheng Mixture to better promote its clinical application. Using LC-MS/MS, 43 components were detected in concentrated Yangzheng Mixture. Six components, comprising astragaloside, calycosin, formononetin, isoquercitrin, ononin, and calycosin-7-O-ß-D-glucoside, were identified in rat plasma. The cancer cell absorption assay showed that the intracellular concentration of four components, calycosin, calycosin-7-O-ß-D-glucoside, formononetin, and ononin, increased with extended incubation time and demonstrated potential anti-tumor effects. The MTT assay results confirmed that Yangzheng Mixture inhibited different tumor cells proliferation. Additionally, the colony formation assay, flow cytometry analysis and wound healing displayed that Yangzheng Mixture and a combination of four components could inhibit colony formation, arrest the cell cycle and impair cell migration of tumor cells, including HCT-116, MHCC-97L, MCF-7 and NCI-H1299. In summary, our study highlighted the plausible application of Yangzheng Mixture as a potential adjuvant treatment for tumors. Furthermore, it identified effective anti-tumor components and provided evidences for the further clinical application of Yangzheng Mixture.

Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-κB signaling in hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major subtype of liver cancer, with a high mortality rate, and close relation to chronic hepatitis. The components of the NLRP3 inflammasome are poorly expressed or even lost in HCC. Downregulation of the NLRP3 inflammasome expression significantly affects the clinical stages and pathological grade of HCC. According to previous research, Shuanghua decoction (SHD), a traditional folk prescription, has an inhibitory effect on nasopharyngeal cancer. PURPOSE: This study aimed to reveal the therapeutic potential of the traditional folk recipe, SHD and its demolition recipe for HCC, and to explore the underlying mechanism. METHODS: The effect of SHD and its demolition recipe on HCC cell biological behaviors was assessed using the MTT assay, colony formation, LDH release assay, KFluor-Edu staining, annexin V-FITC/PI staining assay, Hoechst staining, wound-healing assay, transwell assay, reactive oxygen species (ROS) release assay, HPLC, nude mice model, HE staining, IHC, western blot, and immunofluorescence staining in vitro and in vivo. RESULTS: SHD was found to inhibit HCC, and Oldenlandia and OP (Oldenlandia: Prunella spike = 2.5:1) were identified as the main ingredients that inhibited the proliferation and migration of HCC cells via the activation of the ROS-mediated NLRP3 inflammasome and inhibition of the NF-κB signaling pathway in vitro and in vivo. CONCLUSION: Overall, Chinese medicine theory and pharmacology research revealed that SHD, Oldenlandia and OP may be promising traditional Chinese medicine for the treatment of HCC.

Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs.

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,ß-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Ceftazidime-avibactam in the treatment of infections from carbapenem-resistant Klebsiella pneumoniae: Ceftazidime-avibactam against CR-KP infections.

OBJECTIVES: Clinical experience with ceftazidime-avibactam (CAZ-AVI) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections is not well evaluated. The aim of this study was to assess its efficacy in a single-centre cohort of patients infected with CR-KP. METHODS: We conducted a retrospective observational study of consecutive patients treated for >72 h with CAZ-AVI or other active antibiotics (OAAs) for CR-KP infections. The primary outcome was 30-d mortality. The secondary outcomes were 14-d clinical failure and 14-d microbiological failure. Multivariate regression and propensity score matching were used to evaluate the relationship between CAZ-AVI treatment and outcomes. RESULTS: Ninety infections caused by CR-KP were documented in our study. Forty-two patients were treated with CAZ-AVI and 48 with OAAs. The crude 30-d mortality (8/42 vs. 22/48, P=0.007), 14-d clinical failure (14/42 vs. 24/48, P=0.046) and 14-d microbiological failure (11/42 vs. 15/48, P=0.034) were significantly lower in patients with CAZ-AVI treatment. The Kaplan-Meier survival curves of 30-d mortality confirmed the findings (logrank=0.004). In the multivariable models, the odds ratio (OR) of 30-d mortality (OR 0.23 95% CI 0.10-0.51, P<0.000), 14-d clinical failure (OR 0.37, 95% CI 0.14-0.95, P=0.039) and 14-d microbiological failure (OR 0.17, 95% CI 0.08-0.93, P=0.038) remain consistently significant. In the subgroup analysis, CAZ-AVI was associated with decreased 30-d mortality in the positive blood culture (OR 0.23, 95% CI 0.08-0.63, P=0.004), septic shock (OR 0.23, 95% CI 0.07-0.78, P=0.019), SOFA score (>5, OR 0.13, 95% CI 0.04-0.36, P<0.000), mechanical ventilation (OR 0.13, 95% CI 0.04-0.36, p<0.000) and Charlson comorbidity index (>3, OR 0.15, 95% CI 0.04-0.55, P=0.004). After propensity score matching, 29 cases from each group were well matched. The 30-d mortality remained significantly lower in the CAZ-AVI group (6/29 vs. 13/29, P=0.05). CONCLUSION: CAZ-AVI may be a more valuable therapeutic option for severe CR-KP infections than for mild cases and further randomized controlled trials are needed to evaluate the efficacy.

Microstructure and Mechanical Properties of Laser Welded Al-Si Coated Hot-Press-Forming Steel Joints.

High strength steel has attracted a lot of attention due to its excellent advantage of weight reduction. A thin Al-Si coating covered on the surface of hot-press-forming (HPF) steel offers functions of antioxidation and decarburization under high temperature processing conditions. In this study, the microstructure characteristic, phase, microhardness, and tensile strength of laser welded Al-Si coated HPF steel joints were investigated at different laser powers. Experimental results show that the welding process becomes unstable because of metallic vapor generated by ablation of the coating. Some of the white bright rippled Fe-Al phase was observed to be distributed in the fusion zone randomly. It is found that microhardness, tensile strength, and cupping test qualification rate decreases with the increase of the laser power. For the 1.1 kW laser power, the sound weld performs the best mechanical properties: Microhardness of 466.53 HV and tensile strength of 1349.9 MPa.