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Oxycodone is a common type of opioid used for the treatment of moderate to severe pain. Besides its analgesic effects on neuron cells, the effects of oxycodone on other cell types are yet to be elucidated. We previously demonstrated that oxycodone displayed both pro- and anti-cancer effects on bulk cancer cells. This work further investigated the effects of oxycodone on normal and malignant hematopoietic stem cells. Using hematopoietic CD34+ cells isolated from normal bone marrow (NBM) or patients with acute myeloid leukemia (AML), we showed that oxycodone activates hematopoietic cells regardless of cell development stage and malignant status. Oxycodone dose-dependently increases colony formation and self-renewal capacity of NBM and AML stem/progenitor cells, and promotes proliferation of AML bulk cells. NBM stem/progenitor cells are more sensitive to oxycodone than AML counterparts. In addition, oxycodone alleviates chemotherapy drug-induced toxicity in AML stem/progenitor cells. Mechanism studies demonstrate that oxycodone acts on hematopoietic cells in an opioid-receptor-independent manner. Oxycodone did not affect epithelial growth factor receptor (EGFR) signaling neither but stimulated Wnt/β-catenin signaling. Rescue studies via depleting β-catenin using genetic and pharmacological approaches confirmed that β-catenin was required for the activation of hematopoietic cells induced by oxycodone. Our work demonstrates 1) the protective role of oxycodone in malignant hematopoietic cells from chemotherapy; 2) stimulatory effects of oxycodone in normal hematopoietic stem cells; and 3) ability of oxycodone in Wnt signaling activation.

Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin-binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal was to define glomerular inflammatory events controlled by ABIN1 function in GN. Nephrotoxic serum nephritis was induced in wild-type (WT) and ubiquitin-binding deficient ABIN1[D485N] mice, and renal pathophysiology and glomerular inflammatory phenotypes were assessed. Proteinuria was also measured in ABIN1[D485N] mice transplanted with WT mouse bone marrow. Inflammatory activation of ABIN1[D472N] (D485N homolog) cultured human-derived podocytes, and interaction with primary human neutrophils were also assessed. Disruption of ABIN1 function exacerbated proteinuria, podocyte injury, glomerular NF-κB activity, glomerular expression of inflammatory mediators, and glomerular recruitment and retention of neutrophils in antibody-mediated nephritis. Transplantation of WT bone marrow did not prevent the increased proteinuria in ABIN1[D845N] mice. Tumor necrosis factor–stimulated enhanced expression and secretion of NF-κB–targeted proinflammatory mediators in ABIN1[D472N] cultured podocytes compared with WT cells. Supernatants from ABIN1[D472N] podocytes accelerated chemotaxis of human neutrophils, and ABIN1[D472N] podocytes displayed a greater susceptibility to injurious morphologic findings induced by neutrophil granule contents. These studies define a novel role for ABIN1 dysfunction and NF-κB in mediating GN through proinflammatory activation of podocytes.

There are challenges in developing practically viable biopolymer-based actuators with ecofriendly, biocompatible, and biodegradable functionalities. Therefore, we propose a cellulose acetate (CA)-based ecofriendly soft-ionic networking actuator consisting of multifunctional additive polyvinylidene difluoride (PVDF), highly conductive ammonia-functionalized graphene nanoplatelets (AFGNPs), ionic liquids (IL), and flexible conducting polymer poly(3,4-ethylenedioxuthiopene)-polystyrene sulfonate (PEDOT:PSS) as an electrode. The proposed actuator exhibits a large bending displacement and short response time in an open-air environment, resulting from its enhanced electro-chemo-mechanical properties and strong ionic and interfacial interactions. In comparison with CA/PVDF-IL actuator, the CA/PVDF–IL–AFGNPs actuator demonstrates a considerably increased IL uptake and ion-exchange capacity of up to 71.04% and 300.6%, respectively, and an increase in the specific capacitance by over 3.64 times, which lead to bending actuation performances 2.21 and 1.87 times greater, respectively, under AC (4 V) and DC (4 V). Moreover, we demonstrate that a CA/PVDF–IL–AFGNPs actuator with a hierarchical structure shows values that are 1.32, 1.5, and 1.74 times larger than those of a planar actuator in DC (4 V), AC (3 V), and blocking force (4 V), respectively. The developed high-performance CA/PVDF–AFGNPs and the hierarchical surface texture of the patterned CA/PVDF–IL–AFGNPs actuators present these extraordinary achievements together with environmentally friendly materials, a low driving voltage, easy manufacturing, and high actuation performances. Therefore, they can be candidates for human-friendly products (e.g., biomedical devices, bioinspired robots, and soft haptic devices).

Human epidemiological and animal studies have shown the beneficial effect of zinc supplementation on mitigating diabetic nephropathy. However, the mechanism by which zinc protects the kidney from diabetes remains unknown. Here we demonstrate the therapeutic effects of zinc on diabetes-induced renal pathological and functional changes. These abnormalities were found in both transgenic OVE26 and Akt2-KO diabetic mouse models, accompanied by significant changes in glucose-metabolism-related regulators. The changes included significantly decreased phosphorylation of Akt and GSK-3β, increased phosphorylation of renal glycogen synthase, decreased expression of hexokinase II and PGC-1α, and increased expression of the Akt negative regulators PTEN, PTP1B, and TRB3. All of these were significantly prevented by zinc treatment for 3 months. Furthermore, zinc-stimulated changes in glucose metabolism mediated by Akt were actually found to be metallothionein dependent, but not Akt2 dependent. These results suggest that the therapeutic effects of zinc in diabetic nephropathy are mediated, in part, by the preservation of glucose-metabolism-related pathways via the prevention of diabetes-induced upregulation of Akt negative regulators. Given that zinc deficiency is very common in diabetics, this finding implies that regularly monitoring zinc levels in diabetic patients, as well as supplementing if low, is important in mitigating the development of diabetic nephropathy.