Albrightgrimes6392
Evaluate the effects of maternal high fat and high cholesterol (HFHC) diet consumption on blood pressure (BP), renal function and oxidative stress along the gut-kidney axis in male and female rat offspring.
Pregnant rats were fed with a control (CTL) or HFHC diet during pregnancy and lactation. At 90days, BP was assessed by tail-cuff plethysmography, and urinary and biochemical variables were measured. Biomarkers for oxidative stress, enzymatic antioxidant defense (activity of superoxide dismutase-SOD, catalase, and glutathione-S-transferase-GST) and nonenzymatic antioxidant defense (thiols content) were evaluated in the colon and renal cortex.
Male and female offspring from dams fed with a HFHC diet presented increased BP when compared to their respective CTL group. Male offspring from dams fed with HFHC diet showed reduced GST activity and thiols content in the colon, reduced SOD activity in the renal cortex and decreased urinary creatinine excretion when compared to the CTL group. Regarding female offspring, catalase activity and thiols content were reduced in the colon when compared to CTL group. Although lipid peroxidation had been increased in the renal cortex of HFHC female offspring, the CAT and SOD enzymatic antioxidant acitivities (CAT and SOD) were increased in the renal cortex of female offspring when compared with male offspring; and the renal function was not impaired by maternal HFHC diet consumption.
HFHC diet during pregnancy and lactation induces sex-specific oxidative stress along the gut-kidney axis in offspring, which might induce renal dysfunction and arterial hypertension in later life.
HFHC diet during pregnancy and lactation induces sex-specific oxidative stress along the gut-kidney axis in offspring, which might induce renal dysfunction and arterial hypertension in later life.Exosomes hold great potential for cancer treatment to deliver therapeutics due to its inherent low immunogenicity. Exosomes are biocompatible cell-exocytosed secreted vesicles by most cell types, which can be used to construct novel biomanufacturing platform for drug delivery and cancer therapy. In this study, we implemented nano-sized vesicles which were secreted by mesenchymal stem cell (MSC), to encapsulate doxorubicin (DOX) through electroporation method (DOX@exosome). DOX was loaded into exosomes, with an encapsulation efficiency of up to 35% and separated by ultracentrifugation. Subsequently, carboxylic acid-end MUC1 aptamer was used to covalently decorate the surface amine groups of the exosomes via amide bond formation to provide selective guided drug delivery (DOX@exosome-apt). The data showed that the DOX@exosome-apt provided highly efficient DOX transportation to MUC1-positive cancer cells in vitro as confirmed by MTT and flow cytometry experiments. Moreover, in vivo study on ectopic model of C26 (mouse colon adenocarcinoma) in BALB/c mice indicated that the single dose intravenous injection of DOX@exosome-apt significantly suppress tumor growth in comparison with free DOX. Ex vivo fluorescent imaging also verified the desirable biodistribution of DOX@exosome-apt by exhibiting higher tumor accumulation and faster liver clearance in comparison with DOX@exosome and free DOX. It could be concluded that MUC1 aptamer-decorated exosomes can be implemented therapeutically for the safe and versatile delivery of DOX to colon adenocarcinoma, thus offering valuable platform for clinical applications.
Complement C3 (C3) has been shown to be involved in the aging process. However, the role of C3 in kidney aging has not been fully elucidated. This study aimed to investigate the effect of C3 on senescence related kidney disorders in mice.
Two-, 8-, and 16-month-old C3-deficient male mice (KO) (n=6) and age-, gender-, and strain- matched wild type (WT) C57BL/6 mice (n=6) were selected to represent young, middle-aged and aging mice. Renal, blood and urine samples were collected. Hematoxylin-eosin (HE), Masson, and immunohistochemistry (IHC) staining as well as ELISA and Western blotting were used to explore the mechanisms involved in renal aging.
The level of C3 was upregulated during aging in WT mice. The glomerular sclerosis index and tubulointerstitial fibrosis index were increased significantly in WT mice during aging. Renal function was not significantly different between the young and aged groups. Selleck Tocilizumab Compared with those in WT mice, the levels of inflammation and fibrosis were decreased, while the expression of CD31 was significantly increased in the KO group.
Our data demonstrated that age-related changes in renal structure occur earlier than functional changes and that complement C3 is involved in aging-related kidney disorder.
Our data demonstrated that age-related changes in renal structure occur earlier than functional changes and that complement C3 is involved in aging-related kidney disorder.In sepsis-induced acute kidney injury, kidney blood flow may increase despite decreased glomerular filtration. Normally, angiotensin-II reduces kidney blood flow to maintain filtration. We hypothesized that sepsis reduces angiotensin type-1 receptor (AT1R) expression to account for this observation and tested this hypothesis in a patient case-control study and studies in mice. Seventy-three mice underwent cecal ligation and puncture (a sepsis model) or sham operation. Additionally, 94 septic mice received losartan (selective AT1R antagonist), angiotensin II without or with losartan, or vehicle. Cumulative urine output, kidney blood flow, blood urea nitrogen, and creatinine were measured. AT1R expression was assessed using ELISA, qPCR, and immunofluorescence. A blinded pathologist evaluated tissue for ischemic injury. AT1R expression was compared in autopsy tissue from seven patients with sepsis to that of the non-involved portion of kidney from ten individuals with kidney cancer and three non-infected but critically ill patients. By six hours post ligation/puncture, kidney blood flow doubled, blood urea nitrogen rose, and urine output fell. Concurrently, AT1R expression significantly fell 2-fold in arterioles and the macula densa. Creatinine significantly rose by 24 hours and sham operation did not alter measurements. Losartan significantly exacerbated ligation/puncture-induced changes in kidney blood flow, blood urea nitrogen, creatinine, and urine output. There was no histologic evidence of cortical ischemia. Significantly, angiotensin II prevented changes in kidney blood flow, creatinine, and urine output compared to vehicle. Co-administering losartan with angiotensin-II reversed this protection. Relative to both controls, patients with sepsis had low AT1R expression in arterioles and macula densa. Thus, murine cecal ligation/puncture and clinical sepsis decrease renal AT1R expression. Angiotensin II prevents functional changes while AT1R-blockade exacerbates them independent of ischemia in mice.
