Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/ß-Catenin Signaling.

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/ß-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/ß-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/ß-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/ß-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

Catalytic performance of Ni-Co/HZSM-5 catalysts for aromatic compound promotion in simulated bio-oil upgrading.

Bio-oil can be used as a substitute for fossil fuels after it is upgraded. Bimetal-modified HZSM-5 catalysts with various Ni-to-Co ratios were prepared to address catalysis problems, including deactivation of the catalysts and low hydrocarbon yields. The catalytic performance of Ni-Co/HZSM-5 in upgrading the simulated bio-oil was investigated with a fixed-bed reactor, and the influence of the loaded duplex metal ratio was also discussed. The new moderately strong/strong acid sites of Ni-Co/HZSM-5 changed according to the Ni/Co loading ratios, which substantially affected the acidity, catalytic activity and selectivity of the Ni-Co/HZSM-5. However, incorporating Co and Ni into the zeolite did not alter the structure of the HZSM-5. The interactions of the loaded bimetallic oxides reached equilibrium in 6Ni-4Co/HZSM-5, in which moderately strong acid sites and strong acid sites were formed after loading with Co3O4 and NiO. With a suitable acid site ratio, 6Ni-4Co/HZSM-5 exhibited excellent performance, with a lower coke deposition of 3.29 wt% and stable catalytic activity, and the conversion remained at 83-73% during 360 min of uninterrupted catalysis. Periodic changes in the acid sites and interfacial protons were the critical factors that improved the properties of the 6Ni-4Co/HZSM-5 and enhanced its selectivity for aromatic compounds.

Evaluation of the Impact of Ritlecitinib on Organic Cation Transporters Using Sumatriptan and Biomarkers as Probes.

Ritlecitinib, an inhibitor of Janus kinase 3 and hepatocellular carcinoma family kinases, is in development as potential treatment for several inflammatory diseases. In vitro studies presented ritlecitinib as an inhibitor of hepatic organic cation transporter (OCT) 1, renal transporters OCT2 and multidrug and toxin extrusion (MATE) proteins 1/2K using multiple substrates, and ritlecitinib's major inactive metabolite M2, as an inhibitor of OCT1. A clinical interaction study with an OCT1 drug probe (sumatriptan) and relevant probe biomarkers for OCT/MATE was conducted to assess the effect of ritlecitinib on these transporters in healthy adult participants. The selectivity of sumatriptan for OCT1 was confirmed through a series of in vitro uptake assays. A simple static model was used to help contextualize the observed changes in sumatriptan area under the plasma concentration-time curve (AUC). Coadministration of a single 400-mg dose of ritlecitinib increased sumatriptan AUC from time 0 to infinity (AUCinf ) by ≈30% relative to a single 25-mg sumatriptan administration alone. When administered 8 hours after a ritlecitinib dose, sumatriptan AUCinf increased by ≈50% relative to sumatriptan given alone. Consistent with OCT1 inhibition, the AUC from time 0 to 24 hours of isobutyryl-L-carnitine decreased by ≈15% after ritlecitinib. Based on the evaluation of the renal clearance of N1 -methylnicotinamide, ritlecitinib does not exert clinically meaningful inhibition on renal OCT2 or MATE1/2K. This study confirmed that ritlecitinib and M2 are inhibitors of OCT1 but not OCT2 or MATE1/2K in healthy adults.

Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway.

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 ß, IL-2, IL-6, TNF-α and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.

Evaluation of the Effect of Abrocitinib on Drug Transporters by Integrated Use of Probe Drugs and Endogenous Biomarkers.

Abrocitinib is an oral Janus kinase 1 (JAK1) inhibitor currently approved in the United Kingdom for the treatment of moderate-to-severe atopic dermatitis (AD). As patients with AD may use medications to manage comorbidities, abrocitinib could be used concomitantly with hepatic and/or renal transporter substrates. Therefore, we assessed the potential effect of abrocitinib on probe drugs and endogenous biomarker substrates for the drug transporters of interest. In vitro studies indicated that, among the transporters tested, abrocitinib has the potential to inhibit the activities of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), organic cation transporter 1 (OCT1), and multidrug and toxin extrusion protein 1 and 2K (MATE1/2K). Therefore, subsequent phase I, two-way crossover, open-label studies in healthy participants were performed to assess the impact of abrocitinib on the pharmacokinetics of the transporter probe substrates dabigatran etexilate (P-gp), rosuvastatin (BCRP and OAT3), and metformin (OCT2 and MATE1/2K), as well as endogenous biomarkers for MATE1/2K (N1 -methylnicotinamide (NMN)) and OCT1 (isobutyryl-L -carnitine (IBC)). Co-administration with abrocitinib was shown to increase the plasma exposure of dabigatran by ~ 50%. In comparison, the plasma exposure and renal clearance of rosuvastatin and metformin were not altered with abrocitinib co-administration. Similarly, abrocitinib did not affect the exposure of NMN or IBC. An increase in dabigatran exposure suggests that abrocitinib inhibits P-gp activity. By contrast, a lack of impact on plasma exposure and/or renal clearance of rosuvastatin, metformin, NMN, or IBC suggests that BCRP, OAT3, OCT1, and MATE1/2K activity are unaffected by abrocitinib.

Sulforaphane inhibits the production of Aß partially through the activation of Nrf2-regulated oxidative stress.

Sulforaphane (SFN), a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator, presents a potential role in improving Alzheimer's disease (AD)-specific symptoms. However, the regulation mechanism of SFN in AD is poorly understood. Here, we established AD models both in vitro and in vivo. Animal behaviors were tested by the Morris water maze test. The pathology of the hippocampus and the content of Aß were detected. SFN (40 mg kg-1) decreased the escape latency (24.96 ± 7.43 s) and increased the target-zone frequency (3.19 ± 1.19) in rats. SFN improved the pathological morphology and the number of neurons in the hippocampus. Additionally, SFN significantly upregulated the contents of thioredoxin and glutathione as well as the activities of antioxidant enzymes, along with the expression of the Nrf2 protein. Conversely, SFN lowered the Aß content and ROS level in N2a/APP cells. After silencing the Nrf2 by SiRNA, the inhibitory effects of SFN on ROS and Aß production were partially weakened. In conclusion, the improvement of AD by SFN was closely related with Nrf2 activation.

Anaerobic digestion of corn straw pretreated by ultrasonic combined with aerobic hydrolysis.

Corn straw (CS) was pretreated by ultrasonic combined aerobic with biogas slurry as medium for anaerobic digestion (AD), that strengthened the degradation efficiency CS, varied in the composition of digestion slurry, thereby the methane production was increased. Central combinatorial design (CCD) test was used to treat CS at ultrasonic power (200, 400, and 600 W), time (10, 20, and 30 min) and AD for 25 days, at 37 ± 1℃. According to data showed that the pH and volatile fatty acids (VFAs) affected methane production directly. With an ultrasonic power 309 W, time 26 min, it reached the maximum content of VFAs with 16.24 g/L, the cumulative methane production achieved the highest with 198.56 mL/g VS, which was 46.73% higher than unpretreated raw material as CK. Ultrasonic-aerobic hydrolysis pretreatment can obtain higher VFAs and methane production content in a short period of time that is great significance to biogas engineering.

[Identification and differential expression of miRNA related to seed dormancy of Paris polyphylla var. chinensis].

The purpose of this study was to explore the expression pattern of miRNA in the process of embryo dormancy and provide a reference for the mechanism of regulating seed dormancy and germination by miRNA. We used high-throughput sequencing technology, bioinformatics analysis and real-time fluorescent quantitative PCR(qPCR) technology to sequence, screen and identify miRNAs of dormant and dormant embryos. The results showed that there were 23 811 977, 24 276 695, 20 611 876 and 20 601 811 unique sequences in the four sample libraries during the period of dormancy and dormancy release. MiRNAs are mainly distributed between 21 and 24 nt, among which the length of 24 nt occurred most frequently. A total of 31 known miRNAs were identified, belonging to 13 different families. 93 new miRNAs were predicted by bioinformatics software. Ten miRNAs(mir156 a-5 p, mir160 a-5 p, mir160 h-1, mir169 a-5 p, mir157 d, mir159 a-1, mir395-3, mir156 f-5 p, mir156-2 and mir171 a-3 p) were screened out. In this study, 10 miRNAs related to seed dormancy release were identified. The target genes mainly involved carbohydrate metabolism, plant hormone signal transduction, cell division and growth. The results of qRT-PCR showed that the sequencing results were consistent with the actual results.

Collaborative ISL1/GATA3 interaction in controlling neuroblastoma oncogenic pathways overlapping with but distinct from MYCN.

Background: Transcription factor ISL1 plays a critical role in sympathetic neurogenesis. Expression of ISL1 has been associated with neuroblastoma, a pediatric tumor derived from sympatho-adrenal progenitors, however the role of ISL1 in neuroblastoma remains unexplored. Method: Here, we knocked down ISL1 (KD) in SH-SY5Y neuroblastoma cells and performed RNA-seq and ISL1 ChIP-seq analyses. Results: Analyses of these data revealed that ISL1 acts upstream of multiple oncogenic genes and pathways essential for neuroblastoma proliferation and differentiation, including LMO1 and LIN28B. ISL1 promotes expression of a number of cell cycle associated genes, but represses differentiation associated genes including RA receptors and the downstream target genes EPAS1 and CDKN1A. Consequently, Knockdown of ISL1 inhibits neuroblastoma cell proliferation and migration in vitro and impedes tumor growth in vivo, and enhances neuronal differentiation by RA treatment. Furthermore, genome-wide mapping revealed a substantial co-occupancy of binding regions by ISL1 and GATA3, and ISL1 physically interacts with GATA3, and together they synergistically regulate the aforementioned oncogenic pathways. In addition, analyses of the roles of ISL1 and MYCN in MYCN-amplified and MYCN non-amplified neuroblastoma cells revealed an epistatic relationship between ISL1 and MYCN. ISL1 and MYCN function in parallel to regulate common yet distinct oncogenic pathways in neuroblastoma. Conclusion: Our study has demonstrated that ISL1 plays an essential role in neuroblastoma regulatory networks and may serve as a potential therapeutic target in neuroblastoma.

Unravelling the influence of sulfate loading on enhancing anaerobic co-digestion of corn stover and bio-kerosene production wastewater.

This study was conducted to investigate the effect of sulfate loading on methane production and organic matter degradation during the mesophilic anaerobic co-digestion of corn stover and bio-kerosene production wastewater (BKPW). The highest methane production of 192.04 mL/gVS was obtained at a sulfate concentration of 86 mg/L. This was 46.80% higher than that achieved by a sulfate concentration of 113 mg/L. Additional degradation of organic matter was obtained at a sulfate concentration of 113 mg/L because organic matter in the corn stover and BKPW was oxidized by sulfate-reducing bacteria (SRB). The concentration of sulfate declined by approximately 23% after 29 days of anaerobic co-digestion, and this reduction in sulfate was enhanced when the soluble chemical oxygen demand (SCOD)/sulfate ratio was less than 15. The results of a mass balance analysis showed that 34.87% of C element and 10.04% of S element in substrate, respectively, were converted to biogas during anaerobic co-digestion of corn stover and BKPW at a sulfate concentration of 86 mg/L. The microbial community was analysed using 16S rDNA sequencing technology, and the results showed that the relative abundance of Synergistes (related to methane production with acetic acid) at a sulfate concentration of 86 mg/L had obviously increased and was approximately 287% higher than the abundance achieved at a sulfate concentration of 113 mg/L.

2018 White Paper on Recent Issues in Bioanalysis: 'A global bioanalytical community perspective on last decade of incurred samples reanalysis (ISR)' (Part 1 - small molecule regulated bioanalysis, small molecule biomarkers, peptides & oligonucleotide bioanalysis).

The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LC-MS, hybrid ligand binding assay (LBA)/LC-MS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for LC-MS for small molecules, peptides, oligonucleotides and small molecule biomarkers. Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays) are published in volume 10 of Bioanalysis, issues 23 and 24 (2018), respectively.

Expression of ILK in renal stroma is essential for multiple aspects of renal development.

Kidney development involves reciprocal and inductive interactions between the ureteric bud (UB) and surrounding metanephric mesenchyme. Signals from renal stromal lineages are essential for differentiation and patterning of renal epithelial and mesenchymal cell types and renal vasculogenesis; however, underlying mechanisms remain not fully understood. Integrin-linked kinase (ILK), a key component of integrin signaling pathway, plays an important role in kidney development. However, the role of ILK in renal stroma remains unknown. Here, we ablated ILK in renal stromal lineages using a platelet-derived growth factor receptor B ( Pdgfrb) -Cre mouse line, and the resulting Ilk mutant mice presented postnatal growth retardation and died within 3 wk of age with severe renal developmental defects. Pdgfrb-Cre;Ilk mutant kidneys exhibited a significant decrease in UB branching and disrupted collecting duct formation. From E16.5 onward, renal interstitium was disorganized, forming medullary interstitial pseudocysts. Pdgfrb-Cre;Ilk mutants exhibited renal vasculature mispatterning and impaired glomerular vascular differentiation. Impaired glial cell-derived neurotrophic factor/Ret and bone morphogenetic protein 7 signaling pathways were observed in Pdgfrb-Cre;Ilk mutant kidneys. Furthermore, phosphoproteomic and Western blot analyses revealed a significant dysregulation of a number of key signaling pathways required for kidney morphogenesis, including PI3K/AKT and MAPK/ERK in Pdgfrb-Cre;Ilk mutants. Our results revealed a critical requirement for ILK in renal-stromal and vascular development, as well as a noncell autonomous role of ILK in UB branching morphogenesis.

Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification.

Malformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest lineages. During early development, ISL1 is required for sympathetic neuronal fate determination, differentiation, and repression of glial differentiation, although it is dispensable for initial noradrenergic differentiation. ISL1 also plays an essential role in sympathetic neuron proliferation by controlling cell cycle gene expression. During later development, ISL1 is required for axon growth and sympathetic neuron diversification by maintaining noradrenergic differentiation, but repressing cholinergic differentiation. RNA-seq analyses of sympathetic ganglia from Isl1 mutant and control embryos, together with ISL1 ChIP-seq analysis on sympathetic ganglia, demonstrated that ISL1 regulates directly or indirectly several distinct signaling pathways that orchestrate sympathetic neurogenesis. A number of genes implicated in neuroblastoma pathogenesis are direct downstream targets of ISL1. Our study revealed a temporal requirement for ISL1 in multiple aspects of sympathetic neuron development, and suggested Isl1 as a candidate gene for neuroblastoma.

Effects of Yangzheng Sanjie Decoction-containing serum mediated by microRNA-7 on cell proliferation and apoptosis in gastric cancer.

Gastric cancer (GC) is one of the most common types of cancer and a leading cause of cancer-associated mortality. MicroRNAs (miRNAs/miRs) are demonstrated to function as oncomiRs or tumor-suppressor-miRs in GC. miR-7 has been identified to be a tumor suppressor of GC by targeting epidermal growth factor receptor (EGFR). In our previous study, Yangzheng Sanjie Decoction (YZSJD), a traditional Chinese formula, was identified to be effective in alleviating the symptoms and even postponing turnover of precancerous lesions. To elucidate the mechanism of YZSJD, the present study evaluated the effects of YZSJD of the GC MKN-45 cell line and investigated the underlying molecular mechanisms using YZSJD-containing serum (YCS). The expression of miR-7 in GC, normal and adjacent tissue samples was examined. The results demonstrated that YCS inhibited proliferation by inducing cell cycle arrest at the S phase, and significantly induced apoptosis compared with the control group. miR-7 was significantly downregulated in GC tissues compared with the matched ones. Using reverse transcription-quantitative polymerase chain reaction and western blot analysis, the expression of miR-7 was inversely associated with EGFR. This indicates that YCS inhibits proliferation and induces apoptosis of GC cells mediated by miR-7 targeting EGFR, which may be one of the mechanisms whereby YZSJD exerts its effects on GC.

Yangzheng Sanjie decoction regulates proliferation and apoptosis of gastric cancer cells by enhancing let-7a expression.

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.

Pressurized liquid extraction and cleanup procedure for the determination of pyrethroids in soils using gas chromatography/tandem mass spectrometry.

An analytical method for the simultaneous determination of 12 pyrethroids in soil samples was developed using gas chromatography tandem quadrupole mass spectrometry. Pyrethroids were extracted by pressurized liquid extraction with optimized parameters such as solvent, temperature and extraction time. Then the graphitized carbon black cartridges were used for further purification. The method showed good linearity (R(2) > 0.9931) and good repeatability (RSD < or = 12.6%) for all compounds, with the method detection limits ranging from 0.26 ng g(-1) for transfluthrin to 0.87 ng g(-1) for prallethrin. The recoveries of all compounds were 75-120%.

[The protective effect of PEP-1-SOD1 preconditioning on hypoxia/reoxygenation injury in cultured human umbilical vein endothelial cells].

OBJECTIVE: To construct prokaryotic expression vector of pET15b-PEP-1-SOD1 and investigate whether PEP-1-SOD1 fusion protein could be transduced into human umbilical vein endothelial cells (HUVECs) and the effects on hypoxia/reoxygenation injury. METHODS: The recombinant plasmids pET15b-SOD1 and pET15b-PEP-1-SOD1 were constructed and transformed into E. coli BL21 (DE3) to express SOD1 and PEP-1-SOD1 with an N-terminal His-tag. The purified SOD1 and PEP-1-SOD1 were incubated with HUVECs and the viability (MTT assay) and the release of lactate dehydrogenase (LDH) in culture medium were determined in the hypoxia/reoxygenation injury model. The morphological changes were observed under an inverted phase contrast microscope. The content of malondialdehyde (MDA) in HUVECs was also determined with the method of thiobarbituric acid. RESULTS: PEP-1-SOD1 fusion protein could be transduced into cultured HUVECs in a time- and dose-dependent manner. The intracellular enzymatic activity of PEP-1-SOD1 after 30 min incubation with HUVECs was significantly higher than control group (60.88 U/ml +/- 6.73 U/ml vs. 41.06 U/ml +/- 4.19 U/ml, P < 0.01). The transduced PEP-1-SOD1 protein was enzymatically stable for 24 h within cells. After hypoxia/reoxygenation injury, control HUVECs shrunk, became round-shaped and intercellular space increased, while these morphological changes were not observed in PEP-1-SOD1 transduced HUVECs. PEP-1-SOD1 transduction also markedly increased the viability, decreased LDH leakage into culture media and reduced the content of MDA post hypoxia/reoxygenation. CONCLUSIONS: PEP-1-SOD1 fusion protein could be efficiently transduced into HUVECs in a natively active form, and the delivered enzymatically active PEP-1-SOD1 exhibits cellular protection against hypoxia/reoxygenation injury in HUVECs. The transduction of SOD1 mediated by cell-penetrating peptide, PEP-1, provides a basis for further research on the prevention of ischemia/reperfusion injury in vivo.