An arteriovenous fistula model: Carotid artery-posterior facial vein fistula in rats.

OBJECTIVE: To describe an alternative arteriovenous fistula (AVF) model involving anastomosis of the common carotid artery (CCA) with the posterior facial vein (PFV). METHODS: Twenty-two male Sprague-Dawley rats (age 6-8 weeks) were used to establish the AVF model involving end-to-side anastomosis of PFV and CCA. The peak velocity of the CCA and the diameter of the outflow vein were recorded at 7, 14, and 42 days after the operation using Doppler ultrasound. Pathological examination of the intimal lesions was performed at 14 and 42 days after operation. RESULTS: One rat died within 24 h after surgery related to anesthesia. The patency rates at days 7, 14, and 42 were 85.7%, 81%, and 81%, respectively. The diameter of the carotid artery in rats is approximately 0.8 mm. The diameter of the outflow vein was increased by 1.7-fold and 2.2-fold at 7 days (1.1 ± 0.118 mm) and 14 days (1.4 ± 0.073 mm). At 42 days (1.96 ± 0.101 mm) after operation, the diameter was 3-fold greater compared to the unoperated control rat. The peak systolic flow velocity of the carotid artery at 7 days (593 ± 17.36 mm/s) and 14 days (767 ± 13.64 mm/s) after surgery was significantly greater compared to the control rat (314 ± 15.13 mm/s). The rate of increase was fastest at 7 days and leveled off from 14 to 42 days (875 ± 26 mm/s) after surgery. At 14 days, the intima area showed a nearly 50-fold increase (230 ± 9.93 µm2 × 103) compared to control (area 5 ± 0.37 µm2 × 103). Comparing 6 weeks with 2 weeks (280 ± 10.54 µm2 × 103) after surgery, the intima area increased 1.2 times. CONCLUSION: The CCA-PFV fistula in rats is a viable alternative AVF model.

Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury.

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it's essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI.

Podocyte Infolding Glomerulopathy: A Special Morphology of Podocyte Injury Caused by Heterogeneous Diseases.

Introduction: Podocyte infolding glomerulopathy (PIG) is a newly recognized rare glomerular injury. The clinical significance and mechanism of this injury pattern remains unclear. Methods: We conducted a retrospective study of renal biopsies from January 2018 to December 2020 in Kingmed Diagnostics. The renal biopsy features and clinical data were reviewed. Laser scanning microdissection and mass spectrometry (LMD/MS) was conducted to analyze the potential mechanism. Results: A total of 116 (0.092%) out of 126,086 biopsies were diagnosed as PIG during the period. Of these, 89 (76.7%) cases were found to have PIG coexisting with immune-complex associated glomerulonephritis (IC-PIG) whereas 27 (23.3%) were identified as isolated PIG without immunoglobulin or complement deposition. Systemic lupus erythematosus (SLE), especially with membranous lupus nephritis (LN), was diagnosed in most (70.8%) IC-PIG cases. Of the isolated PIG cases, 51.9% had no known underlying conditions; however, a relatively high positive rate (42.1%) of antinuclear antibody (ANA) was detected. Nearly half (47.5%) of the patients presented with nephrotic syndrome (NS). PIG grade was associated with proteinuria in isolated PIG (P = 0.035). LMD/MS revealed dysregulated cytoskeletal protein α-actinin4 (ACTN4) and tubulin beta-4 chain in PIG compared with normal donor kidney and minimal change disease (MCD). The displacement of ACTN4 into the glomerular basement membrane (GBM) was confirmed by the confocal microscope. Conclusion: PIG is a rare podocyte injury that can exist alone without underlying disease or be concurrent with various diseases, especially SLE. Podocyte cytoskeletal protein ACTN4 and tubulin beta-4 chain were dysregulated, which may be involved in the mechanism of PIG.