Kinetic Characterization and Inhibitor Screening of Pyruvate Kinase I From Babesia microti
In this study, we cloned, expressed, and purified B. microti PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of B. microti with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the Km value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC50 value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of in vitro-cultured B. microti with IC50 values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti-Babesia drugs.
Series Type : Expression profiling by RT-PCROrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below.
ConclusionIpatasertib exhibited rapid absorption and was dose-proportional over a broad dose range. Ipatasertib appeared to be a moderate CYP3A inhibitor when administered at 600 mg and could be administered with or without food in clinical studies.Trail registrationNCT01090960 (registered March 23, 2010); NCT02536391 (registered August 31, 2015).
ConclusionOur study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.
Dr. Laura Esserman answers the door of her bright yellow Victorian home in San Francisco’s Ashbury neighborhood with a phone at her ear. She’s wrapping up one of several meetings that day with her research team at University of California, San Francisco, where she heads the Carol Franc Buck Breast Care Center. She motions me in and reseats herself at a makeshift home office desk in her living room, sandwiched between a grand piano and set of enormous windows overlooking her front yard’s flower garden. It’s her remote base of operations when she’s not seeing patients or operating at the hospita...
Population - attributable fraction varied from 3.9 percent for urinary bladder cancer to 16.9 percent for stomach cancer
In late August, a radiation oncologist in Tampa, Florida, described a distressing first in his career.Medscape Medical News
Patients undergoing gastrointestinal cancer surgery often receive red blood cell (RBC) transfusions. Understanding practice variation is critical to support efforts working towards responsible RBC transfusion use. We aimed to measure the extent and importance of variation in perioperative RBC transfusion use across surgeons and hospitals among gastrointestinal cancer surgery patients.
In Ukraine, there is no established colorectal cancer (CRC) screening program. The healthcare reform provides an opportunity for policymakers to integrate screening recommendations into practice. We aimed to calculate the number of colonoscopies needed for implementation of various well-accepted CRC screening strategies in Ukraine.
While increase of hospital-acquired adverse events (HAAE) after major cancer surgery, there is lack of data correlating them with hospitals markup-ratio (MR). We aim to study the relationship between hospital profit margins and the incidence of HAAE following pancreatic surgery nationally.
Woman,over age 70, compose 30% of breast cancer cases. Over expression of HER2 occurs in 15% of cases. NCCN guidelines recommend systemic treatment for tumors over 1 cm. The Charlson Comorbidity Index can quantify multiple comorbidities and predict a limited life expectancy that allows stratification of women over age 70 who may not benefit from systemic treatment of HER2 breast cancer.