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Objectives: This study aims to investigate the cytotoxicity and sustainable antibacterial activity of unmodified PEEK under specific wavelength light treatment (365 nm), and its antibacterial mechanism was also preliminarily discussed., Methods: A near-ultraviolet source with a wavelength of 365 nm and a power of 5 W were selected. The irradiation time was 30 min, and the distance was 100 mm. A water contact angle tester was used to characterize the surface of the PEEK after 1-15 light treatments. MC3TC-E1 cells were used to evaluate the cytotoxicity of the materials under light treatment. Five kinds of common oral bacteria were detected in vitro, and antibacterial efficiency was determined by colony-forming unit (CFU) and scanning electron microscope (SEM). The antibacterial mechanism of PEEK under light was preliminarily discussed by spectrophotometry. The membrane rupture of Staphylococcus aureus and Escherichia coli was detected by lactate dehydrogenase. Staphylococcus aureus and Staphylococcus mutans were selected for the cyclic antibacterial test. Statistical analysis was performed by one-way analysis of variance and Tukey multiple range test. A significance level of 0.05 was considered (α = 0.05)., Results: The results of the cell experiment showed that PEEK had no cytotoxicity (P > 0.05). CFU results showed that PEEK had an obvious antibacterial effect on Staphylococcus aureus, Staphylococcus mutans, Staphylococcus gordonii and Staphylococcus sanguis, but had no antibacterial effect on Escherichia coli (P < 0.05). The SEM results also verified the above antibacterial effect. The existence of singlet oxygen was confirmed by spectrophotometry. Meanwhile, the rupture of Staphylococcus aureus membrane was verified by lactate dehydrogenase assay. The water contact angle of the PEEK surface did not change significantly after 15 cycles of light treatment. Cyclic antibacterial experiments showed that the antibacterial effect was sustainable., Conclusions: This study showed that PEEK has good cytocompatibility with stable and sustainable antibacterial properties under near-ultraviolet. It provides a new idea to solve the non-antibacterial property of PEEK, and also provides a theoretical basis for its further application in dentistry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pickering emulsions are attracting increased attention owing to their therapeutic applications. However, the slow-release property of Pickering emulsions and the in vivo solid particle accumulation caused by the solid particle stabilizer film limit their applications in therapeutic delivery. In this study, drug-loaded, acid-sensitive Pickering emulsions were prepared using acetal-modified starch-based nanoparticles as stabilizers. The acetalized starch-based nanoparticles (Ace-SNPs) not only act as a solid-particle emulsifier to stabilize Pickering emulsions but also exhibit acid sensitivity and degradability, conducive to the destabilization of Pickering emulsions to release the drug and reduce the effect of particle accumulation in an acidic therapeutic environment. In vitro drug release profiles show that 50 % of curcumin was released in 12 h in an acidic medium (pH 5.4), whereas only 14 % of curcumin was released in 12 h at higher pH (7.4), indicating that the Ace-SNP stabilized Pickering emulsion possess good acid-responsive release characteristics in acidic environments. Moreover, acetalized starch-based nanoparticles and their degradation products showed good biocompatibility, and the resulting curcumin-loaded Pickering emulsions exhibited significant anticancer activity. These features suggest that the acetalized starch-based nanoparticle-stabilized Pickering emulsion has the potential for application as an antitumor drug carrier to enhance therapeutic effects., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Zwitterionic polymers have attracted considerable attention because of their anti-adsorption and unique anti-polyelectrolyte effects and was widely used in surface modification. In this study, zwitterionic copolymers (poly (sulfobetaine methacrylate-co-butyl acrylate) (pSB) coating on the surface of a hydroxylated titanium sheet using surface-initiated atom transfer radical polymerization (SI-ATRP) was successfully constructed. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Water contact angle (WCA) analysis proved the successful preparation of the coating. The swelling effect caused by the anti-polyelectrolyte effect was reflected in the simulation experiment in vitro, and this coating can promote the proliferation and osteogenesis of MC3T3-E1. Therefore, this study provides a new strategy for designing multifunctional biomaterials for implant surface modifications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Podocyte apoptosis plays an important role in the pathogenesis of diabetic nephropathy (DN). Astragaloside IV (AS-IV) has been shown to protect against podocyte apoptosis. Here we aim to investigate the mechanism responsible for the protective effects of AS-IV., Main Methods: Diabetic db/db mice and high glucose (HG)-cultured podocytes were treated with AS-IV. Renal function and histopathological changes were measured to evaluate the therapeutic effects of AS-IV against DN. Adenovirus-mediated Klotho overexpression, Klotho siRNA, and PPARγ inhibitor were applied in vitro to investigate the potential mechanism. The expression levels of mRNA and proteins were analyzed by qRT-PCR, western blot or immunofluorescence. Intracellular ROS and mitochondrial superoxide were detected by DHE and MitoSOx Red, respectively. Cell apoptosis was evaluated by TUNEL staining and flow cytometry., Key Findings: AS-IV improved renal function and ameliorated podocyte injury in db/db mice accompanied with enhanced Klotho expression in glomerular podocytes. In vitro, AS-IV inhibited HG-induced podocyte apoptosis and restored HG-inhibited Klotho expression, whereas Klotho knockdown abrogated the anti-apoptosis action of AS-IV. Further study showed that adenovirus-mediated Klotho overexpression enhanced Forkhead transcription factor O1 (FoxO1)-dependent antioxidant activity and attenuated HG-evoked oxidative stress and apoptosis. AS-IV prevented HG-induced FoxO1 inhibition and oxidative stress, whereas Klotho knockdown reversed these effects. Cotreatment with PPARγ inhibitor T0070907 abolished AS-IV-induced Klotho expression and anti-apoptosis action., Significance: These data suggested that AS-IV attenuated podocyte apoptosis presumably by inhibiting oxidative stress via activating PPARγ-Klotho-FoxO1 signaling pathway, thereby ameliorating DN. This study provided new insights into the molecular mechanisms of AS-IV against DN., (Copyright © 2021. Published by Elsevier Inc.)

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The essential role of membrane associated guanylate kinase 2 (MAGI2) in podocytes is indicated by the phenotypes of severe glomerulosclerosis of both MAGI2 knockout mice and in patients with congenital nephrotic syndrome (CNS) caused by mutations in MAGI2. Here, we show that MAGI2 forms a complex with the Rap1 guanine nucleotide exchange factor, RapGEF2, and that this complex is lost when expressing MAGI2 CNS variants. Co-expression of RapGEF2 with wild-type MAGI2, but not MAGI2 CNS variants, enhanced activation of the small GTPase Rap1, a central signaling node in podocytes. In mice, podocyte-specific RapGEF2 deletion resulted in spontaneous glomerulosclerosis, with qualitative glomerular features comparable to MAGI2 knockout mice. Knockdown of RapGEF2 or MAGI2 in human podocytes caused similar reductions in levels of Rap1 activation and Rap1-mediated downstream signaling. Furthermore, human podocytes expressing MAGI2 CNS variants show severe abnormalities of cellular morphology and dramatic loss of actin cytoskeletal organization, features completely rescued by pharmacological activation of Rap1 via a non-MAGI2 dependent upstream pathway. Finally, immunostaining of kidney sections from patients with congenital nephrotic syndrome and MAGI2 mutations showed reduced podocyte Rap1-mediated signaling. Thus, MAGI2-RapGEF2-Rap1 signaling is essential for normal podocyte function. Hence, disruption of this pathway is an important cause of the renal phenotype induced by MAGI2 CNS mutations., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)