ABSTRACT
OBJECTIVE: To explore the effect of miR-93-mediated Wnt/ß-catenin pathway on the vascular calcification (VC) of chronic renal failure (CRF). METHODS: SD rats were utilized to construct CRF models and divided into Control, CRF, CRF + LV (lentiviral vector)-miR-93 and CRF + LV-Con groups. Renal tissues collected from rats were performed hematoxylin and eosin (HE) staining and Masson staining, while the abdominal aorta was dissected for alizarin red staining and Von Kossa staining. VC-related genes were determined by qRT-PCR while Wnt/ß-catenin pathway-related proteins were examined by Western blotting. RESULTS: As compared to Control group, the serum levels of blood urea nitrogen (BUN), serum creatinine (Scr), phosphorus (P), cystatin C (Cys-C) and 24-h urea protein (24 h Upro), and the scores of renal interstitial lesion and fibrotic area in rats from CRF group were elevated, with the increased calcified area of aorta as well as the enhanced calcium content and ALP. Meanwhile, rats in the CRF group had up-regulated expression of OPN, OCN, RUNX2 and BMP-2 and down-regulated expression of miR-93. As for the expression of Wnt/ß-catenin pathway, rats in the CRF group had sharp increases in the protein expression of TCF4 and ß-catenin, while α-SMA was down-regulated. However, changes of the above were reversed in rats from CRF + LV-miR-93 group, and TCF4 was confirmed to be a target gene of miR-93. CONCLUSION: MiR-93, via inhibiting the activity of Wnt/ß-catenin pathway by targeting TCF4, can improve the renal function of CRF rats, thereby mitigating the vascular calcification of CRF.
Subject(s)
Kidney Failure, Chronic/complications , MicroRNAs/physiology , Vascular Calcification/etiology , Wnt Signaling Pathway/physiology , beta Catenin/physiology , Animals , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms, Male/drug therapy , Breast Neoplasms/drug therapy , Chemotherapy-Induced Febrile Neutropenia/epidemiology , Granulocyte Colony-Stimulating Factor/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Chemotherapy-Induced Febrile Neutropenia/etiology , Chemotherapy-Induced Febrile Neutropenia/prevention & control , China/epidemiology , Drug Administration Schedule , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Progression-Free Survival , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Young AdultABSTRACT
In order to clarify the chemical constituents in Qiliqiangxin capsule, a rapid ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method was established. Forty peaks were identified on line using this method. The herbal sources of these peaks were assigned. The results implied that triterpenoid saponins, flavonoid glycosides, C21-steroids and phenolic acids were included in the main components of Qiliqiangxin capsule. The method is simple and rapid for elucidation of the constituents of Qiliqiangxin capsule and the results are useful for the quality control of Qiliqiangxin capsule.
Subject(s)
Drugs, Chinese Herbal/chemistry , Saponins/analysis , Triterpenes/analysis , Capsules , Chromatography, High Pressure Liquid , Flavones/analysis , Ginsenosides/analysis , Glycosides/analysis , Hydroxybenzoates/analysis , Plants, Medicinal/chemistry , Quality Control , Spectrometry, Mass, Electrospray Ionization , Steroids/analysis , Tandem Mass SpectrometryABSTRACT
OBJECTIVE: To observe the clinical efficacy of shensong yangxin capsule (SYC) on ventricular premature beat (VPB) differentiated in TCM as palpitation of Qi-yin deficiency syndrome or Xin collateral stagnation syndrome, and cardiovascular autonomic nervous function in patients with coronary heart disease (CHD). METHODS: The randomized, double-blind, parallel contrast method was adopted, patients were randomly assigned by 3:1 ratio into two groups. One hundred and sixty-five patients in SYC treated group and 56 in the control group (treated with Xinlvning tablet), and the therapeutic course for both groups was 4 weeks. RESULTS: The clinical efficacy on VPB and in improving TCM syndromes was better in SYC group than that in the control group (P < 0.01). After treatment, the heart rate variability (HRV) and QT dispersion in the two groups were improved in a certain degree. The changes of SDNN, SDANN, SDNN Index and PNN50 in the two groups were significantly different (P < 0.05, P < 0.01), the efficacy in the treated group was superior to that in the control group. CONCLUSION: SYC has definite effect on VPB and TCM Syndromes, it can obviously meliorate the activity of cardiovascular autonomic nervous system in the patients with CHD.