Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Sulfur vacancy-enhanced In2S3-x hollow microtubes for photocatalytic Cr (VI) and tetracycline removal.

Morphological regulation and defect engineering are efficient methods for photocatalytic technology by improving photon absorption and electron dissociation. Herein, In2S3-x hollow microtubes with S-vacancies (MIS) were fabricated via a simple solvothermal reaction using In-based metal-organic frameworks (In-MOFs) as a precursor. Experimental results demonstrate that the hollow structure and optimal S-vacancies can jointly accelerate the photocatalytic reaction, attributed to a larger specific surface area, more active sites, and faster electron transfer efficiency. The champion MIS(2) displayed significantly better photocatalytic activity for Cr(VI) reduction and tetracycline (TC) degradation. The Cr(VI) reduction rate by MIS(2) is 3.67 and 2.82 times higher than those of optimal In2S3 template-free (HIS(2)) and MIS(1) with poor S-vacancies, respectively. The removal efficiency of TC by MIS(2) is 1.37 and 1.15 times higher than those of HIS(2) and MIS(1). Further integration of MIS(2) with aerogel simplifies the recovery process significantly.

Accelerated deterioration corrosion of X70 steel by oxidation acid-producing process catalyzed by Acinetobacter soli in oil-water environment.

Deterioration corrosion occurs between the external surface of oil pipelines and aerobic oil-degrading microorganisms in oil fields. Microorganisms with aerobic oil pollution remediation capabilities may catalyze more serious anaerobic microbial corrosion due to the carbon source supply. In this study, Acinetobacter soli strains were isolated from oil-contaminated environments, and their role in the deterioration corrosion behavior of X70 steel in an oil-water environment was investigated using the EDS multipoint scanning method. The presence of oil controls the deposition of carbon and phosphorus and diffusion of oxygen, leading to significant adhesion attraction and initial growth inhibition of biofilm on the metal surface. A. soli facilitates oxygen transfer and iron ion dissolution, thereby accelerating the pitting corrosion of X70 steel. This corrosion of the X70 steel, in turn, further accelerates the microbial degradation of oil, inhibiting the appearance of calcareous scale in the later stage of corrosion. The corrosion of X70 steel is influenced by microbial degradation, and the specific corrosion behaviors are related to the activity of A. soli in the petroleum environment. This study sheds light on the corrosion mechanisms of X70 steel by A. soli at different stages, providing insights into the interactions between microorganisms, oil pollution, and metal corrosion in oil fields.

Application of Nanomaterials in Stem Cell-Based Therapeutics for Cardiac Repair and Regeneration.

Cardiovascular disease is a leading cause of disability and death worldwide. Although the survival rate of patients with heart diseases can be improved with contemporary pharmacological treatments and surgical procedures, none of these therapies provide a significant improvement in cardiac repair and regeneration. Stem cell-based therapies are a promising approach for functional recovery of damaged myocardium. However, the available stem cells are difficult to differentiate into cardiomyocytes, which result in the extremely low transplantation efficiency. Nanomaterials are widely used to regulate the myocardial differentiation of stem cells, and play a very important role in cardiac tissue engineering. This study discusses the current status and limitations of stem cells and cell-derived exosomes/micro RNAs based cardiac therapy, describes the cardiac repair mechanism of nanomaterials, summarizes the recent advances in nanomaterials used in cardiac repair and regeneration, and evaluates the advantages and disadvantages of the relevant nanomaterials. Besides discussing the potential clinical applications of nanomaterials in cardiac therapy, the perspectives and challenges of nanomaterials used in stem cell-based cardiac repair and regeneration are also considered. Finally, new research directions in this field are proposed, and future research trends are highlighted.

PRELP promotes myocardial fibrosis and ventricular remodelling after acute myocardial infarction by the wnt/ß-catenin signalling pathway.

OBJECTIVES: Proline/arginine-rich end leucine-rich repeat protein (PRELP) has been reported to contribute to the remodelling of cardiovascular tissues in the ischaemia-reperfusion injury model. However, research is lacking on the role of PRELP in myocardial fibrosis and ventricular remodelling, and the mechanism through which PRELP brings about these changes is not clear. This study aimed to evaluate the role of PRELP in ventricular remodelling and myocardial fibrosis following acute myocardial infarction (AMI) and to explore the underlying mechanism. METHODS: In this study, we established AMI mouse and cellculture models in an oxygen-glucose deprivation environment. RESULTS: We found that over-expression of PRELP increased the infarct size and interstitial fibrotic area. Expression of the wnt/ß-catenin pathway molecules, which are downstream of PRELP, increased more in the PRELP over-expression group than in the AMI group. CONCLUSIONS: Our results showed that PRELP, through the wnt/ß-catenin signalling pathway, led to myocardial fibrosis and ventricular remodelling following AMI.

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that leads to respiratory failure, and for which there is no effective treatment. Apolipoprotein A-1 (ApoA-1) has been reported to ameliorate the bleomycin (BLM)-induced IPF model. METHODS: To examine the function of D-4F, an ApoA-1 mimetic polypeptide, in IPF, we used an in-vivo BLM-induced model. We assigned mice into the following 3 groups: the Blank Group (BLK Group), the Bleomycin Treatment Group (Model Group), and the D-4F Interference Group (Inter Group). The BLM-induced fibrosis was examined by hematoxylin and eosin, Masson's trichrome (M-T) staining and immunohistochemical staining. An untargeted lipidomic and transcriptomic analysis were used to examine the function of D-4F. RESULTS: There were 35 differentially altered lipids (DALs) in the BLK, Model and Inter Groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that glycerophospholipid metabolism was the most highly enriched of the 35 DALs. There were 99 differentially expressed genes (DEGs) in the BLK, Model and Inter Groups. The enriched KEGG pathway analysis showed that the mitogen-activated protein kinase (MAPK) pathway was 1 of the top 10 pathways. The results of the untargeted lipidomic and transcriptomic analysis showed that phospholipase A2 group 4c (Pla2g4c) was a crucial gene in both the MAPK pathway and glycerophospholipid metabolism. Pla2g4c was increased in the Model Group but decreased in the Inter Group. CONCLUSIONS: It may be that D-4F prevented the BLM-induced pulmonary fibrosis model by inhibiting the expression of pla2g4c. Our findings suggest that D-4F may be a potential treatment of IPF.

Upconversion nanoparticles/carbon dots (UCNPs@CDs) composite for simultaneous detection and speciation of divalent and trivalent iron ions.

In this study, the application of carbon dots (CDs) modified NaYF4:Yb, Er nanoparticles (UCNPs@CDs) as the fluorescent nanoprobe for simultaneous detection of Fe2+ and Fe3+ was investigated. Fe3+ quantification (5-80 µmol L-1) was achieved, as a result of Fe3+ induced fluorescence quenching of UCNPs@CDs at 434 nm (under the 336 nm excitation). The chelate (Fe2+-phen) formed by Fe2+ and 1,10-phenanthroline had a broad absorption centered at 510 nm, due to inner filter effect (IFE), Fe2+ quantification (4-120 µmol L-1) was achieved as a result of (Fe2+-phen) induced fluorescence quenching of UCNPs@CDs at 545 nm (under the 980 nm excitation). The resultant UCNPs@CDs probe, with excellent anti-interference capability, favorable fluorescence stability, and convincing performance in real sample analysis, showed promising application in simultaneous detection of Fe2+ and Fe3+.

Determination of nitric oxide using light-emitting diode-based colorimeter with tubular porous polypropylene membrane cuvette.

On the basis of the Griess-Saltzman (GS) reaction, an optical device for nitric oxide (NO) detection in exhaled breath and atmosphere was developed by employing the light-emitting diode (LED, 560 nm) as the light source, light-to-voltage converter (LVC) as the detector, and porous polypropylene membrane tube (PPMT) as the cuvette. The PPMT was filled with GS reagents and covered with a coaxial jacket tube for gas collection and color reaction; two ends of the PPMT were connected with the LED and LVC to detect the change of light transmissivity in the wavelength range of 530 to 590 nm mainly. A gas absorber filled with GS reagents was installed prior to another absorber filled with KMnO4 solution to eliminate the interference of coexisting NO2. Under the optimized experimental conditions, the device achieved a limit of detection (3σ/k) of 4.4 ppbv for NO detection. The linearity range of this device was divided into two segments, i.e., 25 to 100 ppbv and 50 to 1000 ppbv, with both coefficients of determination > 0.99. The relative standard deviation was 2.7% (n = 9, c = 100 ppbv), and the analytical time was 5.5 min per detection. The minimum detectable quantity was decreased to 1.18 ng, which was ~ 100 times lower than the original GS method (115 ng). The present device was applied for determination of NO in exhaled breath, vehicle exhaust, and air. In addition to satisfactory spiking recoveries (i.e., 103% and 107%), the analytical results of the present device were in agreement with the results obtained by the standard method. These results assured the practicality of the developed device for NO detection in real environmental samples.

Effects of different dietary polyphenols on conformational changes and functional properties of protein-polyphenol covalent complexes.

In this study, conjugates of whey protein isolate (WPI) and four polyphenols (epigallocatechin gallate [EGCG], quercetin [QC], apigenin [AG], and naringenin [NG]) were prepared through free-radical grafting. The results for polyphenol binding equivalents and content of free amino and sulfhydryl groups as well as those from sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the covalent interaction between WPI and the polyphenols. Fourier transform infrared spectroscopy and fluorescence spectrum analysis identified the potential binding sites of the complexes and determined changes in the protein structure. The particle size distribution and scanning electron microscopy data demonstrated increases in conjugate particle sizes and surface changes in the complexes. The conjugation process significantly increased the polyphenols' antioxidant properties and thermal stabilities, whereas surface hydrophobicity was substantially reduced. WPI-EGCG had the best functional properties, followed by WPI-QC, WPI-AG, and WPI-NG.

EnRank: An Ensemble Method to Detect Pulmonary Hypertension Biomarkers Based on Feature Selection and Machine Learning Models.

Pulmonary hypertension (PH) is a common disease that affects the normal functioning of the human pulmonary arteries. The peripheral blood mononuclear cells (PMBCs) served as an ideal source for a minimally invasive disease diagnosis. This study hypothesized that the transcriptional fluctuations in the PMBCs exposed to the PH arteries may stably reflect the disease. However, the dimension of a human transcriptome is much higher than the number of samples in all the existing datasets. So, an ensemble feature selection algorithm, EnRank, was proposed to integrate the ranking information of four popular feature selection algorithms, i.e., T-test (Ttest), Chi-squared test (Chi2), ridge regression (Ridge), and Least Absolute Shrinkage and Selection Operator (Lasso). Our results suggested that the EnRank-detected biomarkers provided useful information from these four feature selection algorithms and achieved very good prediction accuracy in predicting the PH patients. Many of the EnRank-detected biomarkers were also supported by the literature.

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H2O2 Generation.

Context: The DUOX/DUOXA systems play a key role in H2O2 generation in thyroid cells, which is required for iodine organification and thyroid hormone synthesis. DUOX2/DUOXA2 defects can cause congenital hypothyroidism (CH), but it is unknown whether DUOX1/DUOXA1 mutations can also cause CH. Objective: We aimed to identify DUOX1/DUOXA1 mutations and explore their role in the development of CH by investigating their functional impacts on H2O2 generation. Patients and Methods: Forty-three children with CH with goiter were enrolled, in whom all exons and flanking intronic regions of DUOX1/DUOXA1 were directly sequenced. We characterized the functional effects of identified mutations on the expression of DUOX1 and DUOXA1 and H2O2 generation. Results: We identified a heterozygous DUOX1 missense mutation (G > A base substitution at nucleotide 3920 in exon 31) that changed a highly conserved arginine to glutamine at residual 1307 (p.R1307Q) in patient 1. A heterozygous-missense mutation (c.166 C>T; p.R56W) was identified in DUOXA1 in patient 2. Functional studies demonstrated that both p.R1307Q mutant or p.R56W mutant decreased the DUOX1 expression at mRNA and protein levels, with a corresponding impairment in H2O2 generation (P < 0.01). The results also showed that intact DUOXA1 was required for full activity of DUOX1 and H2O2 generation. Conclusions: We have identified two heterozygous missense mutations in DUOX1 and DUOXA1 in two patients that can cause CH through disrupting the coordination of DUOX1 and DUOXA1 in the generation of H2O2. This study for the first time demonstrates that the DUOX1/DUOXA1 system, if genetically defective, can cause CH.

Bi2Se3 Sensitized TiO2 Nanotube Films for Photogenerated Cathodic Protection of 304 Stainless Steel Under Visible Light.

Titanium dioxide (TiO2) nanotube arrays coupled with a narrow gap semiconductor-bismuth selenide (Bi2Se3)-exhibited remarkable enhancement in the photocathodic protection property for 304 stainless steel under visible light. Bi2Se3/TiO2 nanocomposites were successfully synthesized using a simple two-step method, including an electrochemical anodization method for preparing pure TiO2 and a chemical bath deposition method for synthesizing Bi2Se3 nanoflowers. The morphology and structure of the composite films were studied by scanning electron microscopy, energy dispersion spectroscopy, X-ray photoelectron spectroscopy and X-ray diffraction. In addition, the influence of the Bi2Se3 content on the photoelectrochemical and photocathodic protection properties of the composite films was also studied. The photocurrent density of the Bi2Se3/TiO2 nanocomposites was significantly higher than that of pure TiO2 under visible light. The sensitizer Bi2Se3 enhanced the efficient separation of the photogenerated electron-hole pairs and the photocathodic protection properties of TiO2. Under visible light illumination, Bi2Se3/TiO2 nanocomposites synthesized by the chemical bath deposition method with Bi3+ (0.5 mmol/L) exhibited the optimal photogenerated cathodic protection performance for 304 stainless steel.

Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis.

BACKGROUND: The abnormal expression of certain transcription factors (NKX2.1, FOXE1, NKX2.5, and PAX8) and thyroid stimulating hormone receptor (TSHR) genes has been associated with athyreosis, which is a form of thyroid dysgenesis (TD). We aimed to identify candidate gene mutations in CH patients with athyreosis and to establish the genotype-phenotype correlations in a Chinese population. METHODS: The exons and flanking sequences of NKX2.1, FOXE1, NKX2.5, PAX8, and TSHR were screened by next-generation sequencing and further confirmed by direct Sanger sequencing. The mutation frequencies were calculated and compared against databases. The relationship between genotype and phenotype was also determined. RESULTS: Seven variants were detected in TSHR-p.P52T, p.G132R, p.M164K, p.R450H, p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q, p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected in FOXE1. In addition, one variant (p.N291I) was found in NKX2.5 and two variants (p.A355V and c.-26G>A) were detected in PAX8. CONCLUSIONS: Our study indicated that TSHR mutations have phenotypic variability and has further expanded the mutation spectrum of TSHR. We also revealed that the rate of NKX2.1, FOXE1, NKX2.5, and PAX8 mutations were low in patients with CH and athyreosis, in contrast to the higher rate of TSHR mutations.

Noninvasive Prenatal Diagnosis Significance of ERG Methylation as a Biomarker in Down's Syndrome.

BACKGROUND Down's syndrome (DS) is a genetic disease with chromosome abnormality due to the increasing chromosome 21. This study focused on the clinical application value of ERG methylation level in blood of pregnant women as a biomarker in Down's syndrome. MATERIAL AND METHODS The sham group consisted of 210 nonpregnant women, the positive control group consisted of 33 women with a delivery history of DS fetus, and the negative control group consisted of 60 women with eutocia history. A combination of restriction enzyme digestion experiment and PCR was performed to examine ERG methylation levels, methylation sites, and distribution in blood of pregnant women and in chorion tissues from abortion samples. Gene sequencing was performed to determine the ERG sequence in chromosome 21. Homology between normal tissues and chorion tissues from abortion samples was analyzed with bioinformatics technology. RESULTS ERG methylation in chorion tissues from 210 abortion samples at 8, 9, and 10 weeks gestational age were determined; however, no ERG methylation was determined in blood of pregnant women. Gene sequencing indicated that normal ERG sequence in chromosome 21 was in fetus chorion tissues, and these ERG sequences were aberrantly methylated. Bioinformatics result showed that homology and DNA methylation level was discrepancy in normal tissues and chorion tissues from abortion samples. CONCLUSIONS It was worthwhile to use ERG methylation as biomarker in noninvasive prenatal diagnosis, and ERG methylation should be applied with consent of pregnancy and her relatives.

Somatic copy number losses on chromosome 9q21.33q22.33 encompassing the PTCH1 loci associated with cardiac fibroma.

Cardiac fibroma is an extremely rare benign tumor that remains poorly characterized genetically. Somatic copy number alterations are common in tumors and have been defined as a crucial factor leading to tumors. In this study, we present a child diagnosed with cardiac fibroma with somatic copy number losses of a total of three discontinuous segments from 9q21.33 to 9q22.33, including a mosaic deletion of PTCH1. PTCH1 has been associated with sporadic cardiac fibroma. Sequencing analysis of the PTCH1 gene has not revealed any causative mutation. Quantitative PCR analysis of PTCH1 further confirms somatic copy number losses. Our data narrow down the critical causative deletions for sporadic cardiac fibroma to a region more precise than any other previously reported one. Our results suggest important roles of somatic copy number losses on chromosome 9q21.33q22.33 in the development of sporadic cardiac fibroma; these findings may provide a better understanding of sporadic cardiac fibroma pathogenesis and contribute to the identification of novel diagnostic biomarkers of this neoplasm. .

Association of acylation-stimulating protein and receptor gene polymorphisms with coronary heart disease in Han and Hui populations.

OBJECTIVE: This study was to analyze the acylation-stimulating protein (ASP) (301T>C) and C5a-like receptor 2 (C5L2) (698C>T) gene polymorphisms in Han and Hui populations, and investigate their association with coronary heart disease (CHD). METHODS: 245 Han CHD patients and 110 Hui CHD patients from Shandong, Jinan, China were included in this study. Biochemical analysis was performed to assess the blood sugar and lipid levels in these patients, and the TaqMan genotyping assay was used to determine the genotype distribution. RESULTS: Our results showed that the C allele frequency in the ASP (301T>C) polymorphism in the Hui population was significantly higher than normal controls, while no significant differences were observed in the Han population, which might contribute to the genetic susceptibility of CHD in the Hui population. Moreover, for C5L2 (698C>T) gene polymorphism in both Han and Hui populations, the frequencies of the C/T genotype and T allele were significantly higher in the CHD patients compared with normal controls. Moreover, there were slight differences in the association of ASP and C5L2 gene polymorphisms with blood sugar and lipid levels between Han and Hui populations. CONCLUSIONS: Our results suggest differential ASP and C5L2 genotype distributions between Han and Hui patients, which might be associated with the different CHD-related genetic susceptibilities in these populations. These findings might contribute to a better understanding of the etiology and pathogenesis of CHD in different regions and populations.

Proliferating cell nuclear antigen involved in the repair process of ouabain-induced brain damage independent of hypertension in rats.

BACKGROUND: Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity. It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase. Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen (PCNA) plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis. Therefore, we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension. And PCNA might be involved in this process. METHODS: Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group. Systolic blood pressure was recorded weekly. After four weeks of treatment, morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy. The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry, real time quantitative PCR, and Western blotting. RESULTS: After 4-week treatment, there was no significant difference in systolic blood pressure compared with the control group, but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment. CONCLUSIONS: These results suggest that ouabain induces alterations in the brain structure, and this effect is independent of blood pressure. PCNA might be involved in the repair process of ouabain-induced brain damage.

Profilin-1 promotes the development of hypertension-induced artery remodeling.

Hypertension is associated with the structural remodeling and stiffening of arteries and is known to increase cardiovascular risk. In the present study, we investigated the effects of overexpression and knock down of profilin-1 on the vascular structural remodeling in spontaneous hypertensive rats (SHRs) using an adenovirus injection to knock down or overexpress profilin-1 mRNA. As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). We quantified arterial structural remodeling through morphological methods, with thoracic aortas stained with hematoxylin-eosin and picosirius red. Western blotting was performed to measure the protein expression of inducible nitric oxide synthase (iNOS) and p38 mitogen-activated protein kinase (p38), and peroxynitrite was quantified by immunohistochemical staining. Overexpression of profilin-1 significantly promoted aortic remodeling, including an increase in vessel size, wall thickness, and collagen content, whereas the knockdown of profilin-1 could reverse these effects. In addition, the expression of phosphorylated p38, iNOS and peroxynitrite was significantly upregulated in SHRs with profilin-1 overexpression along with an increased level of interleukin- 6 (IL-6). These changes could be reversed by knockdown of profilin-1. Our results demonstrate a crucial role for profilin-1 in hypertension-induced arterial structural remodeling at least in part through the p38-iNOS-peroxynitrite pathway.