Tumor iron homeostasis and immune regulation.

Abnormal iron metabolism has long been regarded as a key metabolic hallmark of cancer. As a critical cofactor, iron contributes to tumor progression by participating in various processes such as mitochondrial electron transport, gene regulation, and DNA synthesis or repair. Although the role of iron in tumor cells has been widely studied, recent studies have uncovered the interplay of iron metabolism between tumor cells and immune cells, which may affect both innate and adaptive immune responses. In this review, we discuss the current understanding of the regulatory networks of iron metabolism between cancer cells and immune cells and how they contribute to antitumor immunity, and we analyze potential therapeutics targeting iron metabolism. Also, we highlight several key challenges and describe potential therapeutic approaches for future investigations.

Calcitriol combined with high-calcium and high-phosphorus diet induces vascular calcification model in chronic kidney disease rats.

BACKGROUND: Cardiovascular diseases represent a significant complication arising from chronic kidney disease (CKD). Vascular calcification is an important risk factor for cardiovascular diseases. Reducing vascular calcification is therefore critical to reducing mortality in CKD patients. HYPOTHESIS: This study aims to establish a vascular calcification model in rats with CKD by administering subcutaneous injections of calcitriol in combination with a high-calcium and high-phosphorus diet. METHODS: The rats were divided into the CKD vascular calcification model group (subtotal nephrectomy+ [SNx+]) and the sham-operated control group (subtotal nephrectomy- [SNx-]). The rats in the SNx(+) group were administered high-calcium and high-phosphorus feeds following a 5/6 nephrectomy. Calcitriol (1 µg/kg, three times a week) was injected subcutaneously at weeks 0, 4, 8, and 12 after the operation. Measurements of body weight, urine, serum biochemical indicators and vascular calcification level were conducted in rats. RESULTS: (1) Compared with the SNx(-) group, rats in the SNx(+) group experienced an increase in 24-h urine output, urinary phosphorus, and urinary microprotein excretion, along with the development of severe anemia. Additionally, there was a notable elevation in serum phosphorus, blood urea nitrogen, blood creatinine, fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone levels, accompanied by severe hypoproteinemia at week 12. (2) The results of micro-compuyed tomography (µCT) and alizarin S staining of the thoracic aorta demonstrated an increase in vascular calcification in the SNx(+) group. (3) The expression levels of vascular calcification-related proteins were increased. CONCLUSIONS: The administration of calcitriol combined with a high-calcium and high-phosphorus diet was found to induce vascular calcification in CKD rats, leading to a disturbance in mineral metabolism. Vascular calcification was effectively induced in CKD rats after 12 weeks of modeling, thereby presenting a novel approach for establishing a vascular calcification model in CKD rats, helping to elucidate this clinical condition and its underlying molecular mechanisms.

Effects of a closed-loop system against SARS-CoV-2 at the Beijing 2022 Olympic Winter Games: a descriptive and modeling study.

BACKGROUND: To assess the efficacy of the epidemic prevention measures of the "closed-loop" system adopted by the Beijing 2022 Olympic Winter Games (BOWG). METHODS: We retrospectively collected and analyzed information, including age, sex, nationality, vaccination status, date of diagnosis, and date of entry, from 280 SARS-CoV-2-positive individuals identified during the BOWG. A susceptibility-exposed-infectious-remove model was employed to evaluate the effectiveness of epidemic prevention strategies on controlling the spread of SARS-CoV-2 under different scenarios during the BOWG. RESULTS: Regarding SARS-CoV-2-positive cases, 97.9% were imported, and 96.4% were asymptomatic. The median age was 37 years (range: 29-47 years), and 73.9% were male, with the majority of cases being broadcasters and European attendees. Regarding vaccination status, 93.5% were fully vaccinated, and six cases were considered to have been infected in the closed-loop system during the BOWG. Assuming that the BOWG adopted a semi-closed-loop management system, the cumulative number of confirmed cases would be 1,137 for quick quarantine measures (3 d later) implemented and 5,530 for delayed quarantine measures (9 d later) implemented. This modeling revealed that stringent pandemic prevention measures and closed-loop management effectively controlled the spread of SARS-CoV-2 during the BOWG. CONCLUSION: Imported cases are considered the main risk factor for SARS-CoV-2 transmission during mass gatherings, but a comprehensive closed-loop system could minimize transmission among attendees and general personnel.

A Chess and Card Room-Induced COVID-19 Outbreak and Its Agent-Based Simulation in Yangzhou, China.

Objective: To evaluate epidemiological characteristics of the COVID-19 outbreak that resurged in Yangzhou and to simulate the impact of different control measures at different regional scales. Methods: We collected personal information from 570 laboratory-confirmed cases in Yangzhou from 28 July to 26 August 2021, and built a modified susceptible-exposed-infected-removed (SEIR) model and an agent-based model. Results: The SEIR model showed that for passengers from medium-high risk areas, pre-travel nucleic acid testing within 3 days could limit the total number of infected people in Yangzhou to 50; among elderly persons, a 60% increase in vaccination rates could reduce the estimated infections by 253. The agent-based model showed that when the population density of the chess and card room dropped by 40%, the number of infected people would decrease by 54 within 7 days. A ventilation increase in the chess and card room from 25 to 50% could reduce the total number of infections by 33 within 7 days; increasing the ventilation from 25 to 75% could reduce the total number of infections by 63 within 7 days. Conclusions: The SEIR model and agent-based model were used to simulate the impact of different control measures at different regional scales successfully. It is possible to provide references for epidemic prevention and control work.

Intermittent Fasting to the Eye: A New Dimension Involved in Physiological and Pathological Changes.

Intermittent fasting (IF) is gaining popularity as a therapeutic dietary strategy that regulates metabolism and can alter the development of metabolic disorders. An increasing amount of research has connected ocular diseases to IF and discovered that it has a direct and indirect effect on the eye's physiological structure and pathological alterations. This article summarizes the progress of research on IF in regulating the physiological structures of the ocular vasculature, the anterior segment of the eye, the retina, and the choroid. We explored the therapeutic potential of IF for various common ocular diseases. In the future, a comprehensive study into the fundamental processes of IF will provide a direct and rigorous approach to eye disease prevention and therapy.

Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment.

Based on the enhanced knowledge on the tumor microenvironment (TME), a more comprehensive treatment landscape for targeting the TME has emerged. This microenvironment provides multiple therapeutic targets due to its diverse characteristics, leading to numerous TME-targeted strategies. With multifaced activities targeting tumors and the TME, vitamin C is renown as a promising candidate for combination therapy. In this review, we present new advances in how vitamin C reshapes the TME in the immune, hypoxic, metabolic, acidic, neurological, mechanical, and microbial dimensions. These findings will open new possibilities for multiple therapeutic avenues in the fight against cancer. We also review the available preclinical and clinical evidence of vitamin C combined with established therapies, highlighting vitamin C as an adjuvant that can be exploited for novel therapeutics. Finally, we discuss unresolved questions and directions that merit further investigation.

The Analysis of Patterns of Two COVID-19 Outbreak Clusters in China.

Since the emergence of COVID-19, there have been many local outbreaks with foci at shopping malls in China. We compared and analyzed the epidemiological and spatiotemporal characteristics of local COVID-19 outbreaks in two commercial locations, a department store building (DSB) in Baodi District, Tianjin, and the Xinfadi wholesale market (XFD) in Fengtai District, Beijing. The spread of the infection at different times was analyzed by the standard deviation elliptical method. The spatial transfer mode demonstrated that outbreaks started at the center of each commercial location and spread to the periphery. The number of cases and the distance from the central outbreak showed an inverse proportional logarithmic function shape. Most cases were distributed within a 10 km radius; infected individuals who lived far from the outbreak center were mainly infected by close-contact transmission at home or in the workplace. There was no efficient and rapid detection method at the time of the DSB outbreak; the main preventative measure was the timing of COVID-19 precautions. Emergency interventions (closing shopping malls and home isolation) were initiated five days before confirmation of the first case from the shopping center. In contrast, XFD closed after the first confirmed cases appeared, but those infected during this outbreak benefitted from efficient nucleic acid testing. Quick results and isolation of infected individuals were the main methods of epidemic control in this area. The difference in the COVID-19 epidemic patterns between the two shopping malls reflects the progress of Chinese technology in the prevention and control of COVID-19.

Casticin protected against neuronal injury and inhibited the TLR4/NF-κB pathway after middle cerebral artery occlusion in rats.

Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti-inflammatory and anti-tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF-α, TGF-ß, IL-6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF-κB p65, and NF-κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/R-PC12 cells, reduced the expression of TLR4, NF-κB p65, and NF-κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF-κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients.

An evaluation of COVID-19 transmission control in Wenzhou using a modified SEIR model.

In December 2019, the first confirmed case of pneumonia caused by a novel coronavirus was reported. Coronavirus disease 2019 (COVID-19) is currently spreading around the world. The relationships among the pandemic and its associated travel restrictions, social distancing measures, contact tracing, mask-wearing habits and medical consultation efficiency have not yet been extensively assessed. Based on the epidemic data reported by the Health Commission of Wenzhou, we analysed the developmental characteristics of the epidemic and modified the Susceptible-Exposed-Infectious-Removed (SEIR) model in three discrete ways. (1) According to the implemented preventive measures, the epidemic was divided into three stages: initial, outbreak and controlled. (2) We added many factors, such as health protections, travel restrictions and social distancing, close-contact tracing and the time from symptom onset to hospitalisation (TSOH), to the model. (3) Exposed and infected people were subdivided into isolated and free-moving populations. For the parameter estimation of the model, the average TSOH and daily cured cases, deaths and imported cases can be obtained through individual data from epidemiological investigations. The changes in daily contacts are simulated using the intracity travel intensity (ICTI) from the Baidu Migration Big Data platform. The optimal values of the remaining parameters are calculated by the grid search method. With this model, we calculated the sensitivity of the control measures with regard to the prevention of the spread of the epidemic by simulating the number of infected people in various hypothetical situations. Simultaneously, through a simulation of a second epidemic, the challenges from the rebound of the epidemic were analysed, and prevention and control recommendations were made. The results show that the modified SEIR model can effectively simulate the spread of COVID-19 in Wenzhou. The policy of the lockdown of Wuhan, the launch of the first-level Public Health Emergency Preparedness measures on 23 January 2020 and the implementation of resident travel control measures on 31 January 2020 were crucial to COVID-19 control.

3'UTR SNPs in the LPP gene associated with Immunoglobulin A nephropathy risk in the Chinese Han population.

The purpose of this study was to investigate the relationship between Lipoma preferred partner (LPP) gene polymorphisms and the risk of Immunoglobulin A nephropathy (IgAN) in the Chinese Han population. In this case-control study, we genotyped three single nucleotide polymorphisms (SNPs) of the LPP gene in 357 IgAN cases and 384 controls, using Agena Bioscience MassARRAY technology and assessed their association with IgAN using the χ2 test and genetic model analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess risk and were adjusted for age and gender by logistic regression. In the allele model, there were significant associations between LPP rs1064607 (OR = 1.24; 95% CI = 1.01-1.53; p = 0.041), rs3796283 (OR = 1.32; 95% CI = 1.08-1.63; p = 0.008), and rs2378456 (OR = 1.29; 95% CI = 1.05-1.59; p = 0.016), as well as an increased risk of IgAN. In the dominant model, the "G/C-C/C" genotypes of rs1064607 (p = 0.023), the "G/A-G/G" genotypes of rs3796283 (p = 0.0013) and the "G/C-C/C" genotypes of rs2378456 (p = 0.00052) were risk factors for IgAN. The results of the stratified analysis showed that rs3796283 and rs2378456 were connected with susceptibility to IgAN in different subgroups. Our data may provide new evidence to research the etiology of IgAN.

Genetic Variations rs859, rs4646, and rs372883 in the 3'-Untranslated Regions of Genes Are Associated with a Risk of IgA Nephropathy.

BACKGROUND: Previous studies indicate that genetic factors play an important role in the pathogenesis of IgA nephropathy (IgAN). To evaluate the association between single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'-UTR) of genes and IgAN risk, we performed a case-control study in a Chinese Han population. MATERIALS: Twelve SNPs were selected and genotyped in 384 IgAN patients and 357 healthy controls. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender. Multifactor dimensionality reduction (MDR) was used to analyze the interaction of SNP-SNP with IgAN risk. RESULTS: Our study demonstrated that IL-16 rs859 (OR = 0.75, p = 0.040) and CYP19A1 rs4646 (OR = 2.58, p = 0.017) polymorphism were related to the risk of IgAN. In stratified analyses by gender, CYP19A1 rs4646 (OR = 2.96, p = 0.015) and BACH1 rs372883 (OR = 1.81, p = 0.038) polymorphisms conferred susceptibility to IgAN in males. Besides, rs372883 reduced IgAN risk in females (OR = 0.44, p = 0.042). We also found rs859 polymorphism was correlated with grade I-II (OR = 0.42, p = 0.028) in subgroup analysis of Lee's classification. Additionally, we found rs4646 polymorphism was correlated with serum creatinine (p = 0.035). CONCLUSION: Our results suggested that the IL-16 rs859, CYP19A1 rs4646, and BACH1 rs372883 polymorphisms have potential roles in the genetic susceptibility to IgAN in Chinese Han population.

3'UTR variants of TNS3, PHLDB1, NTN4, and GNG2 genes are associated with IgA nephropathy risk in Chinese Han population.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and is characterized by mesangial cell proliferation and agglomeration of the mesangial matrix. METHODS: In this study, we aimed to explore the role of TNS3, PHLDB1, NTN4, and GNG2 3'untranslated region (3'UTR) polymorphisms with the risk of IgAN in a Chinese Han cohort. A logistic recession model was used to calculate the effects of candidate single nucleotide polymorphism (SNP) on IgAN risk after adjusting age and gender difference. In silico prediction was conducted to identify potential functions of SNPs. RESULTS: The analysis revealed a significant relationship between the homozygotic genotype for NTN4 rs1362970 A/A and higher risk of IgAN (p = 0.003). Statistically significant associations were found when the sample was stratified by gender and Lee's grade. As a result, NTN4 rs1362970 A/A and GNG2 rs3204008 G/G genotypes were associated with enhanced IgAN risk in males (p = 0.006, p = 0.023, respectively), and the association between the PHLDB1 rs7389 G/T genotype and higher IgAN risk was found in females (p = 0.008). In the Lee's grade III-V subgroup, the rs1369270 in NTN4 was significantly correlated with the risk of IgAN (p = 0.004). Bioinformatics prediction suggested that rs1362970 within NTN4 3'UTR was located in the potential target sequence of miR-483-5p. CONCLUSIONS: Our research confirmed that NTN4, GNG2, and PHLDB1 gene polymorphisms were implicated in IgAN susceptibility in Chinese Han population. Further research should be conducted to investigate and validate the mechanism by which the above-mentioned polymorphisms affect IgAN.

Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype Grs1800796A rs2069837G rs2069840 (P = 0.037) and G rs1800796A rs2069837C rs2069840 (P = 0.042) in IL-6were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN.

Association between MPHOSPH6 gene polymorphisms and IgA nephropathy risk in a Chinese Han population.

Multiple genetic and environmental factors together contribute to the risk of IgA nephropathy (IgAN). MPHOSPH6 play an important role in the recruitment of the exosome to the pre-rRNA. However, to date, little information is found about the association between MPHOSPH6 polymorphisms and the IgAN risk. In this case-control study, we genotyped five single nucleotide polymorphisms (SNPs) in MPHOSPH6 gene in 416 IgAN cases and 495 controls using Sequenom Mass-ARRAY technology and evaluated their association with IgAN using the χ2 and genetic model analysis. In the allelic model analysis, we determined rs1056654 was associated with a 0.774-fold decrease in the risk of IgAN (95%CI= 0.630-0.952; p = 0.015). In the genetic model analysis, we found that the "C/C" genotype of rs1056675 was associated with an increased risk of IgAN based on the codominant model (OR =1.48; 95% CI=1.03-2.13; p=0.033) and recessive model (OR =1.52; 95% CI=1.11-2.09; p=0.0095). The "G/A-A/A" genotype of rs1056654 was associated with a decreased risk of IgAN based on the dominant model (OR =0.75; 95% CI=0.58-0.98; p=0.032) and log-additvie model (OR =0.78; 95% CI=0.64-0.96; p=0.0188). Our data suggested that gene polymorphisms in the MPHOSPH6 may exert influences IgAN susceptibility in a Chinese Han population.

Association of genetic polymorphisms in IL-1R1 and IL-1R2 genes with IgA nephropathy in the Han Chinese population.

AIM: IgA nephropathy (IgAN) is the major cause of end-stage renal disease(ESRD) in Asia and its pathogenesis is influenced by both genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in IL1R1 and IL-1R2 may be associated with susceptibility to IgAN. In this study, we study the association between genetic variants of IL-1R1 and IL-1R2 and IgA nephropathy risk in the Chinese Han population. RESULT: In the allelic model analysis, the rs10490571 and rs3917225 were associated with a 1.40-fold, and 1.31-fold increased risk of IgA nephropathy, respectively. In the genetic model analysis, the rs10490571 in IL1R1 was associated with a 1.46-fold increased risk of IgAN in the dominant model and 1.36-fold increased risk in the Log-additive model, respectively. However, the rs3218977 in IL1R2 was associated with a 0.71-fold decrease risk of IgAN in the dominant model and a 0.71-fold decrease risk in the over-dominant model, respectively. We found four SNPs (rs11674595, rs4851521, rs719250, and rs3218896) constructed four haplotypes in the IL1R2 gene and none of the haplotype was significantly associated with risk of IgAN. MATERIALS AND METHODS: A case-control study was conducted including 426 nephropathy patients and 463 healthy controls. Chi-squared tests and genetic model were used to evaluate associations. >CONCLUSIONS: These findings suggested that IL-1R1 and IL-1R2 polymorphisms may contribute to the development of IgAN.

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients.

Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA. Compared with healthy controls, CAPD patients had increased TF, PAI-1 protein and mRNA expression by PBMCs at baseline and after stimulated by LPS (10 ng/mL) [p < 0.001]. The fasudil treatment resulted in a significant effect in decreasing TF and PAI-1 [p < 0.05] synthesis in PBMCs. TF and PAI-1 mRNA expression and activities in PBMCs were increased in CAPD patients. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients.

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells.

OBJECTIVE: To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells. METHODS: The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot. RESULTS: AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT. CONCLUSIONS: Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.

Rho kinase pathway is likely responsible for the profibrotic actions of aldosterone in renal epithelial cells via inducing epithelial-mesenchymal transition and extracellular matrix excretion.

It has been demonstrated that aldosterone (ALD) plays a direct profibrotic role in the kidney but the underlying mechanism remains unclear. We examined the role of Rho kinase signal pathway in epithelial-mesenchymal transition (EMT) process and extracellular matirx (ECM) synthesis induced by ALD in human renal proximal tubular epithelial (HK-2) cells in vitro. Rho kinase and collagen I, III protein expressions were detected by ELISA. E-cadherin, α-smooth muscle actin (SMA), collagen_I and collagen III mRNA expressions were detected by real time PCR. E-cadherin, and α-SMA protein expressions were measured by Western blot. Our results showed that ALD could significantly activate the Rho kinase in HK-2 cells, while in the presence of mineralocorticoid receptor (MR) antagonist eplerenone and Rho kinase inhibitor Y27632, the Rho kinase protein expression were almost completely prevented. Exposure of HK-2 cells to ALD for 48 h induced EMT as evidenced by loss of E-cadherin, and de novo expression of α-SMA. The EMT was completely blocked by eplerenone and Y27632. Meanwhile, ALD could significantly increase the mRNA and protein expressions of collagen I, III in HK-2 cells when compared with the control group, while eplerenone and Y27632 could almost reverse these effects. These observations suggest that ALD can activate Rho kinase pathway and Rho kinase pathway is likely responsible for the profibrotic actions of ALD in renal proximal tubular epithelial cells via inducing EMT and ECM excretion.

[Fosinopril up-regulates and ameliorates the Ang II induced down-expression of klotho gene in NRK-52E].

OBJECTIVE: To investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene. METHODS: Culture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively. RESULTS: Fos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E. CONCLUSION: Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.