Influence of thickness and strength on plastic instability in tailored steel structures.

A mathematical model was intricately devised to explore the influence of continuous variations in thickness and mechanical properties on the performance of tailor rolled blanks (TRB) and tailor rolled tubes (TRT). Through the integration of analytical and numerical techniques, it was discerned that these variations play a pivotal role in modulating stress distribution and strain localization, thereby inducing a spectrum of plastic instability behaviors within the structures. The introduction of an 'equivalent strength' metric as a novel means to quantify structural performance shed light on strategic material distribution to enhance durability and mechanical efficiency. Moreover, the insights garnered from this research deepen the understanding of the mechanical responses of tailor-rolled constructs under varying loads, offering valuable perspectives for the development and fabrication of engineered materials with bespoke properties. This study not only contributes to bridging a knowledge gap in the realm of tailored material engineering but also fosters the advancement of design methodologies in the construction of high-performance engineered structures.

Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress.

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

Forming Characteristics of Tailor Rolled Blank of Aluminum Alloy during Three-Point Bending.

This paper presents an investigation on the forming characteristics of the tailor rolled blank of an aluminum alloy (Al-TRB) during three-point bending at room temperature through experiments and finite element simulations. The strain distribution, spring-back characteristics, and metal flow law of 6000 series Al-TRB during three-point bending are explored. The prepared Al-TRB has good bending properties, and no surface cracks appear in the bending region of the Al-TRB when bent to 180°. Surface roughening occurs on the outside of the bending region. Since the strain in the thick zone is greater than that in the thin zone, the surface roughening in the thick zone is more obvious than that in the thin zone. The spring-back angle in the thin zone is higher than that in the thick zone after three-point bending, and the overall spring-back angle of Al-TRB becomes larger with an increasing bending angle. When the transition zone of Al-TRB is centered and the length of the transition zone is certain, as the length of the equal-thickness zone increases, the spring-back angle of the thin zone is larger, while the spring-back angle of the thick zone is smaller. Under the premise of a certain total length of Al-TRB and the length of the transition zone, the larger the length proportion of the thin zone, the larger the overall spring-back angle of Al-TRB, and the larger the length proportion of the thick zone, the smaller the overall spring-back angle of Al-TRB. In addition, a slight metal flow phenomenon exists during three-point bending, which shows that the metal in the bending region will flow to the thick zone, and the metal at the edge will flow to the thin zone. At the same time, there are localized thickening and thinning phenomena in Al-TRB. This study is helpful because it provides theoretical guidance for designing molds for the actual production of Al-TRB parts for automotives.

A bibliometric analysis of metastatic breast cancer: two-decade report (2002-2022).

Background: MBC is a lethal form of breast cancer that arises when cancer cells invade other organs or tissues. The treatment of MBC needs personalized approaches based on the tumor and patient characteristics. The purpose of this paper is to analyze MBC studies from 2002 to 2022 using bibliometrics and to investigate its current situation, main contributors, core journals, highly cited papers, and topic evolution. Materials and methods: We retrieved data from Web of Science Core Collection (WOSCC). Bibliometric analysis of the included literatures mainly used the following tools: the function of "analyze results" and "citation report" in WoS, Microsoft excel 2021, CiteSpace v.6.1. R6, VOSviewer v.1.6.18, BICOMB v.2.04 and gCLUTO v.1.0. Results: We found 12,653 articles on MBC research published in 1, 802 journals by 69, 753 authors from 118 countries. The annual output and citation of MBC articles showed a rising trend over time. The United States was the most influential country in MBC research. The most cited journal in this field was The Journal of Clinical Oncology. And the most cited article was by Slamon DJ. The co-word analysis of keywords divides MBC into six research clusters. The hormone receptor-positive MBC and liquid biopsy of MBC are the frontiers research trends. "CDK4/6 inhibitor" had the highest burst strength. Conclusion: Our bibliometric analysis offers a comprehensive overview of MBC research in the past two decades. It shows the current situation, main contributors, core journals, highly cited papers, and topic evolution of this field. Our study can assist researchers and practitioners to comprehend the development and trends of MBC research and to discover potential directions for future research.

Melatonin Ameliorates Cisplatin-Induced Renal Tubular Epithelial Cell Damage through PPARα/FAO Regulation.

Previous studies revealed that melatonin ameliorated acute renal injury induced by cisplatin, but the mechanisms remain unclear. Peroxidase proliferative receptor α (PPARα) is considered the major regulator of fatty acid oxidation (FAO), which is an important source of energy for renal tubular epithelial cells. In this study, the aim was to investigate the role of melatonin in cisplatin-induced NRK-52E (rat renal tubular epithelial cell line) cell damage and the underlying mechanisms. We established a cisplatin-stimulated NRK-52E model in vitro. We assessed the levels of apoptotic proteins, including caspase-3, caspase-9, and B-cell lymphoma 2-associated X protein (Bax), as well as PPARα and FAO-related genes (Acadm, Acat1, Acsm2, Acsm3, PGC-1α, Pecr, Bdh2, and Echs1). Furthermore, we detected the effects of miR-21 and PPARα antagonist on the above indicators. We found that melatonin reduced the protein expression levels of caspase-3, caspase-9, and Bax, and increased the expression levels of the PPARα gene and protein and PPARα activity, as well as FAO-related genes, in NRK-52E cells. However, miR-21 mimics and PPARα antagonists partially antagonized the above effects of melatonin. Our data indicated that melatonin could alleviate cisplatin-induced cell damage through the upregulation of PPARα/FAO.

Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1.

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and DC-derived extracellular vesicles (DC-EV), triggering systemic antigen-specific T-cell antitumor immunity. Combining VitE with DC-recruiting cancer vaccines or immunogenic chemotherapies greatly boosted ICT efficacy in animals. Therefore, combining VitE supplement or SHP1-inhibited DCs/DC-EVs with DC-enrichment therapies could substantially augment T-cell antitumor immunity and enhance the efficacy of cancer immunotherapies. SIGNIFICANCE: The impacts of nutritional supplements on responses to immunotherapies remain unexplored. Our study revealed that dietary vitamin E binds to and inhibits DC checkpoint SHP1 to increase antigen presentation, prime antitumor T-cell immunity, and enhance immunotherapy efficacy. VitE-treated or SHP1-silenced DCs/DC-EVs could be developed as potent immunotherapies. This article is highlighted in the In This Issue feature, p. 1599.

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

Idiopathic Granulomatous Mastitis: Etiology, Clinical Manifestation, Diagnosis and Treatment.

Idiopathic granulomatous mastitis (IGM) is a rare form of chronic inflammatory breast disease. Although it is a benign breast lesion, it may be sometimes difficult to distinguish from breast cancer. The cause of IGM is unknown, but may be associated with autoimmunity, abnormal hormone levels and infection. While the clinical manifestations of IGM involve various manifestations of inflammation, the diagnosis is principally established by histopathology, characterized by non-caseating granulomas and microabscess formation centered on the breast lobules. Therapeutic options for IGM range from observation to various medical treatments, such as steroids, immunosuppressants, and antibiotics, to surgical intervention, particularly if secondarily infected. Given that the controversy on etiology and treatment choices, we accomplished the present review through reviewing IGM-related literature published in 'Pubmed' and 'Web of science' databases during 1997 to 2020, aiming to provide the basis for rational clinical diagnosis and treatment.

Effects of Cold Rolling Reduction on Microstructure, Thickness, Adhesive Force of Al-Si Coating and on Bending Toughness of Al-Si Coated Press-Hardened Steel.

Al-Si coated press-hardened steel (PHS) is widely used along with the development of light-weight vehicles, and the tailor-rolled blank parts based on Al-Si coated PHS have attracted much attention. The preparation process includes cold rolling, austenitization, hot-stamping, and quenching. The most widely used AS60/60 coating will change after cold rolling and austenitization, which has been little-studied. Herein, the effects of cold rolling reduction on the microstructure, thickness, adhesive force of AS60/60 coating and on bending toughness of AS60/60 coated PHS were studied. As the cold rolling reduction ratio increased from 0% to 50%, the coatings were gradually thinned, but the overall continuity was unchanged. When the reduction ratio was 40% or above, rapid diffusion channels were formed. The adhesive force of coatings was 21.50-22.15 MPa. After austenitization, the coating thickness gradually decreased as the cold rolling reduction ratio rose from 0% to 50%, but the structure and overall continuity were both unchanged, and the adhesive force was 21.60-22.40 MPa. The rapid diffusion channels promoted the transition from brittle Fe2Al5 to tough FeAl during austenitization, leading to a rapid increment in bending toughness after Al-Si coated PHS was quenched. When the reduction ratio was 50%, the bending angle was improved by 23%.

Comprehensive Genomic Characterization Analysis Identifies an Oncogenic Pseudogene RP11-3543B.1 in Human Gastric Cancer.

Background: Gastrointestinal Cancer (GICs) is the most common group of malignancies, and many of its types are the leading causes of cancer related death worldwide. Pseudogenes have been revealed to have critical regulatory roles in human cancers. The objective of this study is to comprehensive characterize the pseudogenes expression profiling and identify key pseudogenes in the development of gastric cancer (GC). Methods: The pseudogenes expression profiling was analyzed in six types of GICs cancer from The Cancer Genome Atlas RNA-seq data to identify GICs cancer related pseudogenes. Meanwhile, the genomic characterization including somatic alterations of pseudogenes was analyzed. Then, CCK8 and colony formation assays were performed to evaluate the biological function of RP11-3543B.1 and miR-145 in gastric cancer cells. The mechanisms of pseudogene RP11-3543B.1 in GC cells were explored via using bioinformatics analysis, next generation sequencing and lucifarese reporter assay. Results: We identified a great number of pseudogenes with significantly altered expression in GICs, and some of these pseudogenes expressed differently among the six cancer types. The amplification or deletion in the pseudogenes-containing loci involved in the alterations of pseudogenes expression in GICs. Among these altered pseudogenes, RP11-3543B.1 is significantly upregulated in gastric cancer. Down-regulation of RP11-3543B.1 expression impaired GC cells proliferation both in vitro and in vivo. RP11-3543B.1 exerts oncogene function via targeting miR-145-5p to regulate MAPK4 expression in gastric cancer cells. Conclusion: Our study reveals the potential of pseudogenes expression as a new paradigm for investigating GI cancer tumorigenesis and discovering prognostic biomarkers for patients.

Integrated genomic analysis reveals regulatory pathways and dynamic landscapes of the tRNA transcriptome.

tRNAs and tRNA-derived RNA fragments (tRFs) play various roles in many cellular processes outside of protein synthesis. However, comprehensive investigations of tRNA/tRF regulation are rare. In this study, we used new algorithms to extensively analyze the publicly available data from 1332 ChIP-Seq and 42 small-RNA-Seq experiments in human cell lines and tissues to investigate the transcriptional and posttranscriptional regulatory mechanisms of tRNAs. We found that histone acetylation, cAMP, and pluripotency pathways play important roles in the regulation of the tRNA gene transcription in a cell-specific manner. Analysis of RNA-Seq data identified 950 high-confidence tRFs, and the results suggested that tRNA pools are dramatically distinct across the samples in terms of expression profiles and tRF composition. The mismatch analysis identified new potential modification sites and specific modification patterns in tRNA families. The results also show that RNA library preparation technologies have a considerable impact on tRNA profiling and need to be optimized in the future.

Ginsenoside Rb1 ameliorates autophagy via the AMPK/mTOR pathway in renal tubular epithelial cells in vitro and in vivo.

Although ginsenoside Rb1 (G-Rb1) has exerted an inhibitory effect on renal fibrosis and progression of chronic kidney disease (CKD), its mechanism remains unknown. This study aims to explore the anti-fibrosis effect of G-Rb1 in unilateral ureter obstruction (UUO) mouse model and underlying mechanisms in HBSS-induced HK-2 cells. In vivo, renal function, kidney histological pathology, and autophagy-related protein molecules were assessed. Additionally, rapamycin, Deptor overexpression plasmid, Akt inhibitor, metformin, and a p38-MAPK inhibitor, as well as an ERK-MAPK inhibitor were used to evaluate the effect of AMPK/mTOR, Akt and MAPK signal pathways on the protective effect of G-Rb1 in HK-2 cells. Treatment with G-Rb1 significantly improved renal dysfunction. G-Rb1 reversed UUO-induced downregulation of p62, and upregulation of LC3 and the ratio of LC3 I/II, indicating that G-Rb1 restrained UUO-induced activation of autophagy. Furthermore, we found that treatment of HBSS-induced HK-2 cells with G-Rb1 resulted in AMPK/mTOR and ERK, p38 MAPKs signaling pathways regulated autophagy inhibition. These findings may explain, in part, the molecular mechanisms by which G-Rb1 could be applied in the treatment of patients with CKD, further suggesting that autophagy and its associated molecular signaling pathway may be new targets for the treatment of renal fibrosis and CKD.

Pyruvate kinase M2 is a marker of poor prognosis in lung adenocarcinoma but not lung squamous cell carcinoma.

BACKGROUND: To explore the pyruvate kinase M2 (PKM2) expression profile as a prognostic marker of lung adenocarcinoma (LUAD) as well as lung squamous cell carcinoma (LUSC). METHODS: Retrospective bioinformatics analysis of data from the Cancer Genome Atlas-Lung Cancer dataset and the Human Protein Atlas was performed. PKM2 mRNA expression was monitored using the Kaplan-Meier Plotter online database. GraphPad Prism 6.0 and the SPSS 19.0 software package were used for statistical analysis. RESULTS: PKM2 expression was found to be significantly higher in both LUAD and LUSC than in normal controls. Although increased PKM2 expression in LUAD was correlated with poor overall survival (OS) [hazard ratio (HR): 2.128; 95% CI: 1.754-3.653; P<0.001], recurrence-free survival (RFS) (HR: 1.524; 95% CI: 1.069-2.499; P=0.0237), and progression-free survival (PFS) (HR: 2.18; 95% CI: 1.58-3; P<0.001), no such associations were found in LUSC. CONCLUSIONS: PKM2 is a potential prognostic biomarker for LUAD but not for LUSC.

Measurements of Temperature Distribution for High Temperature Steel Plates Based on Digital Image Correlation.

Temperature distribution is an important process parameter of steel plates during electromagnetic induction heating treatment. This study uses the digital image correlation method to develop an effective non-contact temperature measurement that allows obtaining valuable information about the temperature value of a high temperature steel plate specimen and analyzing its temperature distribution. A principle of thermal radiation temperature measurement based on the color chagre couled device (CCD) technology was introduced. The image processing system encapsulates the image update module, form mode module, image event module and temperature analysis module. The error analysis and temperature calibration were carried out to make sure the error deviation of the measurement system was within a small range. The temperature distribution of B1500HS at high temperature was analyzed by the designed measurement system which was in good agreement with the result from Raynger 3i Plus temperature gun, indicating that the measurement system based on image processing basically meets the requirements of temperature distribution measurement of a high temperature steel plate, and provides an important reference for a high temperature steel plate in non-contact temperature distribution measurement.

The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin.

Phagocytosis of various targets, such as apoptotic cells or opsonized pathogens, by macrophages is coordinated by a complex signaling network initiated by distinct phagocytic receptors. Despite the different initial signaling pathways, each pathway ends up regulating the actin cytoskeletal network, phagosome formation and closure, and phagosome maturation leading to degradation of the engulfed particle. Herein, we describe a new phagocytic function for the nucleoside diphosphate kinase 1 (NDK-1), the nematode counterpart of the first identified metastasis inhibitor NM23-H1 (nonmetastatic clone number 23) nonmetastatic clone number 23 or nonmetastatic isoform 1 (NME1). We reveal by coimmunoprecipitation, Duolink proximity ligation assay, and mass spectrometry that NDK-1/NME1 works in a complex with DYN-1/Dynamin (Caenorhabditis elegans/human homolog proteins), which is essential for engulfment and phagosome maturation. Time-lapse microscopy shows that NDK-1 is expressed on phagosomal surfaces during cell corpse clearance in the same time window as DYN-1. Silencing of NM23-M1 in mouse bone marrow-derived macrophages resulted in decreased phagocytosis of apoptotic thymocytes. In human macrophages, NM23-H1 and Dynamin are corecruited at sites of phagosome formation in F-actin-rich cups. In addition, NM23-H1 was required for efficient phagocytosis. Together, our data demonstrate that NDK-1/NME1 is an evolutionarily conserved element of successful phagocytosis.-Farkas, Z., Petric, M., Liu, X., Herit, F., Rajnavölgyi, É., Szondy, Z., Budai, Z., Orbán, T. I., Sándor, S., Mehta, A., Bajtay, Z., Kovács, T., Jung, S. Y., Afaq Shakir, M., Qin, J., Zhou, Z., Niedergang, F., Boissan, M., Takács-Vellai, K. The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/dynamin.

CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma.

CBX3, namely chromobox protein homolog 3, a member of the heterochomatin protein 1 (HP1) family, has been shown to be associated with the tumorigenesis of various types of cancer. The aim of the present study was to assess the biological role and the clinicopathological importance of CBX3 in osteosarcoma. The Oncomine database was utilized to determine the CBX3 expression in sarcoma patients. A retrospective cohort study was conducted to evaluate the prognostic value of CBX3 expression. In addition, correlations between the clinicopathological features of the osteosarcoma patients and CBX3 expression were assessed and involved recurrence, distant metastasis, lymph node metastasis, response to chemotherapy, pathological differentiation, clinical stage, anatomic location, tumor size and age. To investigate the function of CBX3 in osteosarcoma, a small interfering RNA for CBX3 was designed and this was used for the transfection of osteosarcoma MG63 cells. Then, the effects of CBX3 on proliferation, cell cycle distribution and apoptosis of osteosarcoma cells were investigated via CCK­8 assay and cell cycle assay and cell apoptosis analysis, respectively. Based on our findings, upregulation of CBX3 expression was noted both in osteosarcoma and also other sarcoma types, which included pleomorphic liposarcoma, myxofibrosarcoma, myxoid/round cell liposarcoma and dedifferentiated liposarcoma. In addition, based on the retrospective cohort study, CBX3 expression was associated with the disease­free survival (DFS) and overall survival (OS) of the osteosarcoma patients and a large tumor size, high distant metastasis rate and high clinical stage rate. In addition, the proliferation ability was blocked by the knockdown of CBX3 through the application of CBX3 siRNA, and CBX3 knockdown also led to increased apoptosis and cell cycle arrest at G0 and G1 phases in osteosarcoma cells. CBX3 is highly expressed in human osteosarcoma tissues. Meanwhile, high CBX3 is a predictor of the poor prognosis of osteosarcoma patients. To conclude, the growth of osteosarcoma can be promoted by CBX3, which may be used as an independent potential prognostic biomarker for patients suffering from osteosarcoma.

Dispersion Characteristics of Hazardous Gas and Exposure Risk Assessment in a Multiroom Building Environment.

The leakage of hazardous chemicals during storage and transport processes is a kind of commonly occurring accident that can pose a serious threat to people's lives and property. This paper aims to investigate the airflow and dispersion characteristics of hazardous gas around a multiroom building, and evaluate the corresponding exposure risks. The effects on indoor air quality (IAQ) when polluted air enters a room under different indoor and external conditions were examined by using a computational fluid dynamics technique. First, the numerical model established herein was verified by the available wind-tunnel experimental data, and acceptable agreement was found between the predicted and measured velocities. Subsequently, the effects of different natural ventilation paths, wall porosities and outdoor pollutant source characteristics on the airflow and contaminant distribution were evaluated. The study not only reveals the airflow pattern and concentration distribution in indoor spaces under different natural ventilation conditions but also quantitatively analyzes the relationship between the probability of death and the corresponding source strength under the circumstance of pollutant leakage near a building. The results can be useful for the prevention and control of hazardous chemical gas leakages and provide some guidance on evacuation after an accidental or routine leakage.

MKP2 inhibits TGF-ß1-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells through a JNK-dependent pathway.

Epithelial-to-mesenchymal transition (EMT) is a phenotypic conversion that plays a crucial role in renal fibrosis leading to chronic renal failure. Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate the MAP kinase pathway involved in transforming growth factor-ß1 (TGF-ß1)-induced EMT. However, the function of MKP2 in the regulation of EMT and the underlying mechanisms are still largely unknown. In the present study, we detected the expression of MKP2 in an animal model of renal fibrosis and evaluated the potential role of MKP2 in tubular EMT induced by TGF-ß1. We found that the expression of MKP2 was up-regulated in the tubular epithelial of unilateral ureter obstruction rats. Meanwhile, we also demonstrated that TGF-ß1 up-regulated MKP2 expression in NRK-52E cells during their EMT phenotype acquisition. Importantly, overexpression of MKP2 inhibited c-Jun amino terminal kinase (JNK) signaling and partially reversed EMT induced by TGF-ß1. Moreover, reducing MKP2 expression enhanced JNK phosphorylation, promoted the E-cadherin suppression and induced α-SMA expression and fibronectin secretion in response to TGF-ß1, which could be rescued by a JNK inhibitor. These results provide the first evidence that MKP2 is a negative feedback molecule induced by TGF-ß1, and MKP2 overexpression inhibits TGF-ß1-induced EMT through the JNK signaling pathway. MKP2 could be a promising target to be used in gene therapy for renal fibrosis.

Semaphorin-3A and Netrin-1 predict the development of kidney injury in children with congenital hydronephrosis.

Congenital obstructive nephropathy is amongst the main causes of chronic renal failure in children. Early diagnosis and initiation of the treatment will delay progressive renal tubular atrophy and interstitial fibrosis with the loss of nephrons. The aim of this study was to evaluate whether urinary (u) semaphorin-3A (SEMA-3A) and Netrin-1 may be potential biomarkers in children with congenital hydronephrosis due to ureteropelvic junction obstruction (UPJO). The study consisted of 42 children with severe hydronephrosis who needed surgery and two control groups (Control One: 42 children with mild, non-obstructive hydronephrosis; Control Two: 44 healthy children). All children had normal renal function. Urinary semaphorin-3A and Netrin-1 levels were measured in different groups using immunoenzymatic ELISA commercial kits. Compared with Control One and Control Two groups, the preoperative median uSEMA-3A/creatinine (cr.) and uNetrin-1/cr. levels increased significantly in the children with severe hydronephrosis (p < .01). One month after surgery, uSEMA-3A/cr. and uNetrin-1/cr. levels had decreased significantly in the children with severe hydronephrosis (p < .01), but were still higher than those in both control groups (p < .05). Receiver operator characteristic (ROC) analyses revealed a good diagnostic profile for uSEMA-3A and uNetrin-1 in terms of identifying children with a differential renal function of <40% [area under the curve (AUC) 0.825 and 0.745, respectively]. Our results indicate that increased concentrations of uSEMA-3A and uNetrin-1 are found in urine from children with severe hydronephrosis and that their concentrations are related to the degree of obstruction.