Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences

Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end-stage renal disease. In addition, low birth weight and low nephron number are associated with increased risk for CKD. This study examined the development and severity of unilateral ureter obstruction (UUO)-induced renal fibrosis in male and female wild-type (ROP +/+) and mutant (ROP Os/+) mice, a mouse model of low nephron number. Methods: Male and female ROP +/+ and ROP Os/+ mice were subjected to UUO, and kidney tissue was collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. Results: Male and female UUO mice demonstrated marked renal injury, kidney fibrosis, and renal extracellular matrix production. Renal fibrosis and α-smooth muscle actin were increased to a similar degree in ROP +/+ and ROP Os/+ mice with UUO of either sex. There were also no sex differences in renal tubular cast formation or renal infiltration of macrophage in ROP +/+ and ROP Os/+ UUO mice. Interestingly, renal fibrosis and α-smooth muscle actin were 1.5–3-fold greater in UUO-ROP +/+ compared to UUO-ROP Os/+ mice. Renal inflammation phenotypes following UUO were also 30–45% greater in ROP +/+ compared to ROP Os/+ mice. Likewise, expression of extracellular matrix and renal fibrotic genes was greater in UUO-ROP +/+ mice compared to UUO-ROP Os/+ mice. In contrast to these findings, ROP Os/+ mice with UUO demonstrated glomerular hypertrophy with 50% greater glomerular tuft area compared to ROP +/+ with UUO. Glomerular hypertrophy was not sex-dependent in any of the genotypes of ROP mice. These findings provide evidence that low nephron number contributes to UUO-induced glomerular hypertrophy in ROP Os/+ mice but does not enhance renal fibrosis, inflammation, and renal tubular injury. Conclusion: Taken together, we demonstrate that low nephron number contributes to enhanced glomerular hypertrophy but not kidney fibrosis and tubular injury. We also demonstrate that none of the changes caused by UUO was affected by sex in any of the ROP mice genotypes

Green formulation, chemical characterization and anti-acute leukemia effects of vanadium nanoparticles containing Foeniculum vulgare extract

In this study, vanadium nanoparticles (VNPs) were green synthesized using Foeniculum vulgare extract. VNPs were characterized using chemical analysis techniques including FT-IR, XRD, FE-SEM, TEM and EDS. The microscopy techniques revealed a spherical morphology for the particles with size less than 50 nm. According to XRD data V2O5 was confirmed for VNPs. Maybe significant anti-human acute leukemia potentials of the synthesized nanoparticles against common human acute leukemia cell lines are linked to their antioxidant activities. MTT assay was used on common acute leukemia cell lines i.e., 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 to survey the cytotoxicity and anti-acute leukemia effects of the synthesized nanoparticles. The synthesized nanoparticles had very low cell viability and high anti-acute leukemia activities dose-dependently against 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 cell lines without cytotoxicity on the normal cell line (HUVEC). To determine the antioxidant properties of the synthesized nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The IC50 of VNPs were 25, 33 and 26 µg/mL against 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 cell lines, respectively. The synthesized nanoparticles inhibited half of the DPPH molecules in the concentration of 28 µg/mL

Introducing a novel and natural antibiotic for the treatment of oral pathogens: Abelmoschus esculentus green-formulated silver nanoparticles

Nanotechnology can solve many biomedical problems and cause transformation in the field of health and pharmaceuticals. The use of this technology in removing pathogenic bacteria is of great interest. The introduction of a strong antibacterial agent is very important to control pathogenic bacteria, especially strains resistant to antibiotics. The aim of this research was to synthesize silver nanoparticles (AgNPs) with the help of Abelmoschus esculentus aqueous extract and investigate its antibacterial properties against oral pathogens. Our study examined the ability of AgNPs to inhibit the dental bacterial growth and anti-adherence in vitro. The biosynthesized AgNPs@Abelmoschus esculentus were characterized by FT-IR, UV–Vis, and SEM tests. The physical and chemical investigation of the synthesized AgNPs showed that the particles were produced in nano dimensions, spherical shape, and without any impurities. In antibacterial test, the 8 µg/mL exhibited the lowest minimum inhibitory concentrations (MICs) against Porphyromonas gingivalis and Streptococcus mutans (MIC = 8 µg/mL). In vitro adherence of S. mutans was significantly prevented by AgNPs@Abelmoschus esculentus (MIC = 8–16 µg/mL). According to the results, the AgNPs@Abelmoschus esculentus may be good candidates for the oral hygiene agents to prevent periodontopathic conditions and dental caries

557 Dual TGFβR1/MAP4K4 inhibitor reduces kidney injury in a mouse model of renal fibrosis.

OBJECTIVES/GOALS: Renal fibrosis is a critical pathophysiological event in chronic kidney diseases. Our goal is to determine the ability of dual-inhibitor of transforming growth factor beta receptor 1 (TGFα²R1) and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), TK850, on reducing kidney fibrosis. METHODS/STUDY POPULATION: To test the renal anti-fibrotic action ofdual TK850,8-10-week-old male and female C57BL/6mice with unilateral ureteral obstruction (UUO) induced kidney fibrosis were used. Mice were separated into 3 groups: group 1 contained mice that had UUO surgery (UUO control), group 2 contained mice prophylactically treated with TK850 thatstarted 7 days prior to UUO(UUO-P,20 mpk/d/ip), and group 3 contained mice interventionally treated with TK850 that started3 days after UUO(UUO-I,20 mpk/d/ip). Ten days following UUO the kidneys and blood were collected for analysis. Renal fibrosis was assessed from hydroxyproline content (measure of collagen)and histological collagen analysis using Picrosirius red stain. RESULTS/ANTICIPATED RESULTS: Renal hydroxyproline was increased equally in the UUO kidney of male (5.4 ± 0.41 µg/10mg, n=5) and female mice (5.5 ± 0.50 µg/10mg, n=5) compared to the contralateral control kidney (2.9 ± 0.14 µg/10mg, n=10). TK850 treatment in UUO-P mice (n=10, 3.4 ± 0.24 µg/10mg) and UUO-I mice (4.30 ± 0.20 µg/10mg, n=10) had significantly reduced hydroxyproline levels. Histopathological evaluation revealed that kidney injury increased collagen deposition in the UUO kidney (17.1 ± 0.43% collagen positive area, n=10) compared to the control kidney (2.0 ± 0.23%, n=10). TK850 treatment in UUO-P mice significantly attenuated collagen deposition (10.5 ± 0.38%, n=10), while UUO-I had significantly reduced collagen deposition as well (13.1 ± 0.25%, n=10). DISCUSSION/SIGNIFICANCE: Taken together, these results validate the dual TGFβR1/MAP4K4 inhibitor, TK850 as a potential therapeutic to mitigate renal fibrosis and supports the emergence of a combinational pharmacotherapeutic approach for multi-factorial kidney diseases

Green synthesis of silver nanoparticles from aqueous extract of Ziziphora clinopodioides Lam and evaluation of their bio-activities under in vitro and in vivo conditions

© 2020 John Wiley & Sons, Ltd. The purpose of this experiment was the green synthesis of silver nanoparticles from aqueous extracts of Ziziphora clinopodioides Lam (AgNPs@Ziziphora) and assessment of their cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound-healing effects. These nanoparticles were characterized using ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction (XRD), field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FESEM-EDX), atomic force microscopy (AFM), and transmission electron microscopy (TEM). UV–Vis, TEM, and FESEM analyses indicated that the size of Ag nanoparticles (AgNPs) depended on Z. clinopodioides and AgNO3 concentrations. In vitro biological experiments indicated that AgNPs@Ziziphora has excellent antioxidant potential against DPPH, antifungal effects against Candida guilliermondii, Candida krusei, Candida glabrata, and Candida albicans, and antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Streptococcus pneumonia, Salmonella typhimurium, Pseudomonas aeruginosa, and Escherichia coli O157:H7. Also, these nanoparticles did not exhibit cytotoxicity property against human umbilical vein endothelial cells (HUVECs). An in vivo biological test revealed that AgNPs@Ziziphora ointment significantly (p ≤ 0.01) increased the levels of wound contracture, blood vessels, hydroxyl proline, hexuronic acid, hexosamine, fibrocytes, fibroblasts, and fibrocyte/fibroblast ratio and significantly (p ≤ 0.01) decreased the wound area, and levels of total cells, neutrophils, and lymphocytes than other groups in rats. The results of UV–Vis, XRD, FESEM-EDX, AFM, and TEM confirmed that the aqueous extract of Z. clinopodioides can be used to produce silver nanoparticles with significant antioxidant, antimicrobial, and cutaneous wound-healing properties without any cytotoxicity