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For this purpose, four different PLGA NPs were prepared and analyzed (i) "PLGA@Drug," in which a model drug was encapsulated in its core; (ii) "8D3-PLGA" NPs where the PLGA surface was functionalized with a monoclonal anti-transferrin receptor antibody (8D3 mAb) in order to specifically target the BBB; (iii) "8D3-PLGA@Drug" in which the PLGA@Drug surface was functionalized using the same antibody described above and (iv) bare PLGA NPs which were used as a control. Once the anticipated protein corona NPs were obtained, proteins decorating both bare and functionalized PLGA NPs were isolated and analyzed. Apart from the indistinct interaction with PLGA NPs with the most abundant serum proteins, specific proteins could also be identified in the case of functionalized PLGA NPs. These findings may provide valuable insight into designing novel vehicles based on PLGA NPs for crossing the BBB.Hematopoietic cell transplantation generates new individuals, transplant chimeras, composed of 2 genetic partners-the patient and donor-derived cells-no longer restricted by their original genomes. Interactions of donor-derived and recipient cells occur prominently at the boundary of the recipient with a third partner, the microbiome, in particular skin and intestinal tract, leading to disruption of microbiome homeostasis. These interactions of donor and patient cells at the boundary set the stage for the development of graft-versus-host disease, an expression of the defense of individuality by recipient and donor. Establishment of tolerance and return of homeostasis at the boundary will allow for the survival of the new integrated, physiologic individual.<br /><br /> Nonalcoholic fatty liver disease (NAFLD) is a complication of pancreaticoduodenectomy (PD). We conducted a randomized clinical trial to determine if high-dose digestive enzymes prevented the development of NAFLD after PD.<br /><br /> This parallel-group, nonblinded, multicenter study enrolled patients undergoing elective PD at Shinshu University School of Medicine, from June 2011 to April 2017. Patients were randomly assigned to receive normal-dose (Excelase 3.0 g/day [Meiji Seika Pharma Holdings Co, Ltd]) or high-dose digestive enzyme treatment (Excelase 3.0 g/day; Pancreatin [Tokyo Chemical Industry Co Ltd] 3.0 g/day; Berizym [Kyowa Pharmaceutical Industry Co Ltd] 3.0 g/day; and Toughmac-E [Ono Pharmaceutical Co, Ltd] 3.0 g/day) within 1 week after surgery. Because patients in the control group switched interventions upon receiving a diagnosis of NAFLD, intention-to-treat analysis was used. [https://www.selleckchem.com/products/ly3200882.html buy LY 3200882] The primary endpoint was incidence of NAFLD within 1 year, and the secondary endpoints were the incidences of NAFLD at 1, 3, 6n.ac.jp/ctr/).<br /><br />High-dose administration of digestive enzymes significantly reduced the onset of NAFLD after PD compared with normal-dose administration. Registration number UMIN000005595 (http//www.umin.ac.jp/ctr/).Drug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.The purpose of the present study was to quantitatively predict the negative food effect induced by bile micelle binding on the oral absorption of hydrophilic cationic drugs. The intrinsic membrane permeability and bile micelle unbound fraction of 12 model drugs (7 tertiary amines, 3 quaternary ammoniums, and 2 neutral drugs) were calculated from the experimental Caco-2 permeability data (Papp) under fasted and fed conditions. From these input data, the fraction of a dose absorbed (Fa) was predicted using the gastrointestinal unified theoretical framework, a mechanism-based oral absorption model. The predicted Fa ratio (fed/fasted) was then compared with the in vivo fed/fasted area under the plasma concentration-time curve ratio (AUCr). The AUCr values of tertiary amines and neutral drugs were appropriately predicted (absolute average fold error (AAFE) = 1.19), whereas those of quaternary ammoniums were markedly underestimated (AAFE = 4.70). The Papp ratio (fed/fasted) predicted AUCr less quantitatively (AAFE = 1.30 for tertiary amines and neutral drugs). The results of the present study would lead to a better understanding of negative food effect on oral drug absorption.<br /><br /> Biliverdin, a by-product of haem catabolism, possesses potent endogenous antioxidant and anti-inflammatory properties. Bilirubin-C10-sulfonate (BRS), an active metabolite formed after enteral administration of BV in the rat, also possess antioxidant properties. Therefore, we investigated the anti-inflammatory and antioxidant activity of BV and BRS in an in vivo model of monosodium urate induced sterile inflammation.<br /><br /> Subcutaneous air pouches were created on the dorsal flanks of Wistar rats (10-12 weeks of age). Prior to stimulation of the 6-day old pouch with monosodium urate (25mg), groups were pre-treated with intraperitoneal BRS (27mg/kg) and BV (27mg/kg). Total and differential leukocyte counts were determined in pouch fluid aspirate at 1, 6, 12, 24 and 48h after monosodium urate stimulation. Biliverdin (BV), BRS and unconjugated bilirubin (UCB) concentrations in the serum and pouch fluid were quantified using liquid chromatography-mass spectrometry. Pouch fluid cytokine concentrations (IL-1β, IL-1α, TNF-α, IL-17A, IL-12, GM-CSF, IL-33, IFN-γ, IL-18, IL-10, MCP-1, CXCL-1 and IL-6) were assessed after 6h.