Corn oligopeptides inhibit Akt/NF-κB signaling pathway and inflammatory factors to ameliorate CCl4 -induced hepatic fibrosis in mice.

In this study, the effect of corn oligopeptides (COPs) with liver protection activity on mice with hepatic fibrosis (HF) induced by carbon tetrachloride (CCl4 ) was studied. It was proved that COPs can ameliorate the liver injury and inflammation caused by CCl4 by histopathology and enzyme-linked immunosorbent assay in mice. The expression of Akt/NF-κB inflammatory pathway was determined by real-time polymerase chain reaction (RT-PCR) and western blotting (WB). The results showed that COPs inhibited the expression of key proteins in the inflammatory pathway. In conclusion, the results of this study suggested that COPs could improve CCl4 -induced HF by improving liver injury, reducing the expression of inflammatory factors, and inhibiting the expression of inflammatory signaling pathways. PRACTICAL APPLICATIONS: The corns around the world are mainly used as animal feed, and the liver protective activity of corn oligopeptides (COPs) is rarely applied to the market. The development of COPs liver protective food can prevent the occurrence of liver-related diseases such as hepatic fibrosis to a certain extent. Developing COPs liver protecting food can improve the utilization value of corn. It is hoped that this study can provide experimental support for the application of COPs in liver protection food.

Caloric restriction inhibits renal artery ageing by reducing endothelin-1 expression.

BACKGROUND: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression. METHODS: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-ß1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis. RESULTS: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1ß, TNF-α, and TGF-ß1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats. CONCLUSIONS: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction.

Effect of Shexiang Baoxin Pill () in Alleviating Early Hypertensive Renal Injury in Rats.

OBJECTIVE: To investigate the effect of Shexiang Baoxin Pill (, SBP) on early hypertensive renal injury in rats and to explore the possible mechanism. METHODS: Twelve-week-old spontaneous hypertensive rats (SHRs) with high-salt diet (dietary containing 8% NaCl) were randomized into the SBP group [40 mg/(kg·d)], losartan potassium group [20 mg/(kg·d)] and saline group by stratified random sampling method, 12 in each group. Blood pressure and urea albumin creatinine ratio were measured. After 10 weeks, the expression levels of serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1 ß, IL-6, tumor necrosis factor α (TNF-α), and transforming growth factor ß (TGF-ß) in serum were assessed. Kidney pathology periodate-schiff staining was performed. Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining. Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), monocyte chemokine peptide (MCP-1), inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). RESULTS: SBP did not affect the mortality of SHR (P<0.05). SBP significantly reduced the level of elevated blood pressure of SHRs, but the effect was less significantly than that of losartan potassium. SBP decreased urine protein (P<0.01) and the expression levels of IL-1 ß, IL-6, TNF-α, and TGF-ß in serum. The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells, glomerular ischemic lesions, inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis. Both SBP and losartan potassium had alleviated renal pathological change, and significantly reduced the infiltration of macrophage (P<0.05, P<0.01). SBP and losartan potassium decreased the expressions of TLR4, NF-κB, MCP-1, iNOS, and Arg-1. CONCLUSION: SBP significantly modified the early hypertensive renal injury by reducing inflammation, and the effect was similar to losartan potassium.

[Effects of kidney stem cells on injure-recovery of human renal tubular epithelial cells].

OBJECTIVE: To investigate the protective effects and the mechanism of kidney stem cells (KSC) on the injured tubular epithelial cells. METHODS: KSC were isolated from rat renal papilla. The human kidney epithelial cells (HKC) injury model was induced with 0.1 µmol/L antimycin A for 30 minutes. The injured HKC were co-cultured with KSC or supernatant of cultured KSC. The apoptosis of HKC were detected by flow cytometry. The changes of ATP in the HKC and the level of malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) in the supernatant of cultured HKC were detected after being co-cultured with KSC. RESULTS: The study of the co-culture showed that KSC was less capable to migrate through the micropores of Transwell compared with bone marrow stem cells. However, after being co-cultured with the KSC conditional supernatant, ATP content of injured HKC, total SOD value in the supernatant of injured HKC were increased, and the MDA and LDH in the supernatant of injured HKC decreased. CONCLUSION: KSC have protected effects and participate in the repair of injured HKC.

[Stem cells and diabetic nephropathy].

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetic mellitus. Its treatment by now is mainly focused on the suppression of the renin-angiotonin system and the control of relative risk factors such as hypertension, hyperglycemia and so on, whose effectiveness is disappointed. Stem cells can be found in almost all organs and tissues, the main functional characteristics of stem cells are their capacity for self-renewal, the differentiation into several other cell types, and their immunomodulatory ability. In this article, we review the potential of stem cells as new therapeutic agents in the treatment of DN, discuss about how the diabetic environment affects these cells, and the therapeutic benefits that these stem cells offer for treating DN, suggesting that stem cells therapies might represent a new and promising strategy for the treatment of DN.

[Long-term follow-up of elderly patients with atherosclerotic renal artery stenosis treated by percutaneous transluminal angioplasty with stent implantation].

OBJECTIVE: To evaluate the long-term effects of percutaneous transluminal renal angioplasty with stent (PTRAS) on hypertension and renal function in elderly patients with atherosclerotic renal artery stenosis (ARAS). METHODS: The data of elderly ARAS patients as diagnosed by angiography (stenosis ≥ 70%) were retrospectively collected. PTRAS was performed in 65 patients. The average follow-up period was 30.9 months. RESULTS: There were significant decrease in BP (blood pressure, mm Hg, 1 mm Hg = 0.133 kPa) (before: 154 ± 24/ 79 ± 119 vs after: 132 ± 14/69 ± 8; P < 0.01) at Day 3 post-PTRAS and the decrease of BP continued until 36 months after PTRAS. The average category of antihypertensive medication also decreased from 2.3 ± 1.1 to 2.1 ± 1.0. The incidence of contrast-induced nephropathy (CIN) was 9.2%. Logistic regression analysis showed that the factors of pre-operative diabetes mellitus, GFR ≤ 30 ml×min(-1)·1.73 m(-2), systolic pressure ≥ 180 mm Hg and hydration therapy had a significant relationship with the incidence of CIN (P = 0.0072; OR = 13.51; P = 0.0002; OR = 519.27; P = 0.0134; OR = 13.16 and P = 0.0266; OR = 0.10; respectively). Renal function improved in 9.1%-15.8% of patients, stabilized in 67.3% - 55.3% and deteriorated in 23.4% - 28.9% of patients at Months 12 - 36 post-PTRAS. Logistic regression analysis showed that the diabetics had a higher risk of deteriorating renal function at month 12 post-PTRAS (P = 0.0277; OR = 6.32). The restenosis rate was 13.8%. CONCLUSION: PTRAS is beneficial in the control of blood pressure in elderly ARAS patients within 36 months after operation. The post-PTRAS improvement of renal function in elderly patients is limited.

Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors.

The glomeruli of postmenopausal C57BL6 mice, and age-matched males, show progressive hypertrophy and glomerulosclerosis. We asked whether this was a multistage process, was due to alterations in glomerular progenitors, and was reversible in female mice. Using cross bone marrow transplants (BMT) between young and old females, we found that BMT delivered a phenotype that was donor age-specific. The fact that lesions in young recipients were more severe if the donors were in late rather than early menopause suggested that new progenitor phenotypes had appeared. Postmenopausal recipients of BMT from young donors had reduced glomerular hypertrophy and sclerosis, implying that the aging lesions in females were reversible and that progenitors, rather than the local environment, determined the glomerular profile. The altered phenotype included increased extracellular matrix synthesis and decreased matrix metalloproteinase-2 levels as well as cell hypertrophy. The mechanism of the cellular hypertrophy was due to uncoupling of hypertrophy from proliferation, resulting from elevated p27 levels. Thus, glomerular hypertrophy and sclerosis in aging females is a multistage process, is reversible, and may be determined by the phenotype of bone marrow-derived progenitor cells.

The glomerulosclerosis of aging in females: contribution of the proinflammatory mesangial cell phenotype to macrophage infiltration.

Age-associated renal changes may be an important cause of renal failure. We recently found that aged female B6 mice developed progressive glomerular lesions. This was associated with macrophage infiltration, a frequent finding in glomerulosclerosis. We used these mice as a model for studying the mechanisms of glomerular aging. We compared the gene expression profile of intact glomeruli from late postmenopausal (28-month-old) mice to that of intact glomeruli from premenopausal (5-month-old) mice. We found that inflammation-related genes, especially those expressed by activated macrophages, were up-regulated in the glomeruli of 28-month-old mice, a result correlating with the histological observation of glomerular macrophage infiltration. The mechanism for macrophage recruitment could have been stable phenotypic changes in mesangial cells because we found that mesangial cells isolated from 28-month-old mice expressed higher levels of RANTES and VCAM-1 than cells from 5-month-old mice. The elevated serum tumor necrosis factor (TNF)-alpha levels present in aged mice may contribute to increased RANTES and VCAM-1 expression in mesangial cells. Furthermore, cells from 28-month-old mice were more sensitive to TNF-alpha-induced RANTES and VCAM-1 up-regulation. The effect of TNF-alpha on RANTES expression was mediated by TNF receptor 1. Interestingly, mesangial cells isolated from 28-month-old mice had increased nuclear factor-kappaB transcriptional activity. Inhibition of nuclear factor-kappaB activity decreased baseline as well as TNF-alpha-induced RANTES and VCAM-1 expression in mesangial cells isolated from 28-month-old mice. Thus, phenotypic changes in mesangial cells may predispose them to inflammatory stimuli, such as TNF-alpha, which would contribute to glomerular macrophage infiltration and inflammatory lesions in aging.

Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: the role of mesangial cell progenitors.

The pathologic hallmarks of diabetic nephropathy are excess mesangial extracellular matrix (ECM) and mesangial cell proliferation. We previously showed that mesangial cell phenotypic changes play an important role in the pathogenesis of diabetic nephropathy. We concluded that phenotypic changes were present in bone marrow (BM)-derived mesangial cell progenitors, as transplantation of BM from db/db mice, a model of type 2 diabetic nephropathy, transferred the db genotype and a nephropathy phenotype to naive B6 mice recipients. The recipients did not develop diabetes; however, they did develop albuminuria and glomerular lesions mirroring those in the donors (i.e., glomerular hypertrophy, increased ECM, and increased cell number with cell proliferation). We found that matrix metalloproteinase 2 (MMP-2) facilitated invasion of the mesangial cells into ECM and proliferation in vitro. Thus, increased MMP-2 activity in db/db mesangial cell progenitors may partially explain increased mesangial cell repopulation and proliferation in B6 recipients of db/db BM. In summary, BM-derived mesangial cell progenitors may play a crucial role in the development and progression of ECM accumulation and mesangial cell proliferation in this model of diabetic nephropathy in type 2 diabetes.