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Background Ileal neobladder fistula is a rare complication after radical cystectomy, with an incidence of approximately 0.7%. At present, there are scattered reports of vesicoileal fistula, but there are no reports of ileal neobladder fistula (INF) caused by bladder stones. In this paper, a case of ileal neobladder fistula caused by chronic stimulation of bladder stones was successfully diagnosed and treated. Case presentation A 68-year-old man who had undergone radical cystectomy and an orthotopic ileal neobladder procedure 10 years prior presented with refractory diarrhoea and oliguria and was diagnosed with ileal neobladder fistula caused by chronic stimulation of bladder stones. We performed fistulectomy, cystotomy, partial ileectomy, and end-to-end ileal anastomosis, and the patient recovered and was discharged after the operation. Conclusion Urinary calculi are delayed complications of orthotopic neobladder construction after total cystectomy. Bladder stones are a rare complication of ileal neovesical fistula, which can cause neovesical cutaneous fistula. It is difficult to diagnose through routine examination and easily misdiagnosed as acute gastroenteritis. Surgery is an effective treatment for INF and can achieve a good prognosis.

Although organic nanomaterials and inorganic nanoparticles possess inherent flexibility, facilitating functional modification, increased intracellular uptake and controllable drug release, their underlying cytotoxicity and lack of specificity still cause safety concerns. Owing to their merits, which include natural biocompatibility, structural stability, unsurpassed programmability, ease of internalization and editable functionality, tetrahedral DNA nanostructures show promising potential as an alternative vehicle for drug delivery and biomedical treatment. Here, we describe the design, fabrication, purification, characterization and potential biomedical applications of a self-assembling tetrahedral DNA nanostructure (TDN)-based multifunctional delivery system. First, relying on Watson-Crick base pairing, four single DNA strands form a simple and typical pyramid structure via one hybridization step. Then, the protocol details four different modification approaches, including replacing a short sequence of a single DNA strand by an antisense peptide nucleic acid, appending an aptamer to the vertex, direct incubation with small-molecular-weight drugs such as paclitaxel and wogonin and coating with protective agents such as cationic polymers. These modified TDN-based complexes promote the intracellular uptake and biostability of the delivered molecules, and show promise in the fields of targeted therapy, antibacterial and anticancer treatment and tissue regeneration. The entire duration of assembly and characterization depends on the cargo type and modification method, which takes from 2 h to 3 d.

DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With the rapid progress in DNA nanotechnology, multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson-Crick base-pairing for molecular self-assembly. Some DNA materials could functionally change cell biological behaviors, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNAs (ssDNAs) or RNAs with secondary structures via self-pairing, named aptamer, possess the ability of targeting, which are selected by systematic evolution of ligands by exponential enrichment (SELEX) and applied for tumor targeted diagnosis and treatment. Some DNA nanomaterials with three-dimensional (3D) nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic agents. While the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies, and also proved with great potential in the biological and medical use, there is still a long way to go for the eventual application of DNA materials in real life. Here in this review, we conducted a comprehensive survey of the structural development history of various DNA nanomaterials, introduced the principles of different DNA nanomaterials, summarized their biological applications in different fields, and discussed the current challenges and further directions that could help to achieve their applications in the future., This work was supported in part by National Key R&D Program of China (Grant Nos. 2019YFA0110600) and National Natural Science Foundation of China (Grant Nos. 81970916 and 81671031).

Aim Tissue engineering has been recognised as one of the most effective means to form a new viable tissue for medical purpose. Tissue engineering involves a combination of scaffolds, cells, suitable biochemical and physicochemical factors, and engineering and materials methods. This review covered some biomedicine, such as biomaterials, bioactive factors, and stem cells, and manufacturing technologies used in tissue engineering in the oral maxillofacial region, especially in China. Materials and methods Data for this review were identified by searches of Web of Science and PubMed, and references from relevant articles using the search terms "biomaterials", "oral tissue regeneration", "bioactive factors" and "stem cells". Only articles published in English between 2013 and 2018 were included. Conclusion The combination of stem cells, bioactive factors and 3D scaffolds could be of far-reaching significance for the future therapies in tissue repair or tissue regeneration. Furthermore, the review also mentions issues that need to be solved in the application of these biomedicines.

Recently, a DNA tetrahedron has been reported to be a novel nanomedicine and promising drug vector because of its compactness, biocompatibility, biosafety, and editability. Here, we modified the DNA tetrahedron with a DNA aptamer (AS1411) as a DNA-based delivery system, which could bind to nucleolin for its cancer cell selectivity. Nucleolin is a specific biomarker protein overexpressed on membranes of malignant cancer cells and its deregulation is implicated in cell proliferation. The antimetabolite drug 5-fluorouracil (5-FU) is an extensively used anticancer agent; however, its major limitation is the lack of target specificity. Cyanine 5 (Cy5), a fluorescent probe, can be used to label DNA tetrahedron and enhance photostability with minimal effects on its basic functions. In this study, we additionally attached 5-FU to the DNA-based delivery system as a new tumor-targeting nanomedicine (AS1411-T-5-FU) to enhance the therapeutic efficacy and targeting of breast cancer. We examined the difference of the cellular uptake of AS1411-T-5-FU between breast cancer cells and normal breast cells and concluded that AS1411-T-5-FU had a better targeting ability to kill breast cancer cells than 5-FU. We further evaluated the expressions of cell apoptosis-related proteins and genes, which are associated with the mitochondrial apoptotic pathway. Ultimately, our results suggest the potential of DNA tetrahedron in cancer therapies, and we develop a novel approach to endow 5-FU with targeting property.

The overuse of antibiotics has led to the emergence of multidrug-resistant pathogens. There is an urgent need to develop alternative therapeutic strategies to reduce mortality and morbidity related to drug-resistant bacterial infections. Self-synthesized tetrahedral framework nucleic acids (tFNAs) are used as the drug loading platform to deliver ampicillin to combat methicillin-resistant

Cartilage, as a nanostructured tissue, because of its awfully poor capacity for inherent regeneration and complete hierarchical structure, is severely difficult to regenerate after damages. Tissue engineering methods have provided a great contribution for cartilage repair. Nanomaterials have special superiority in regulating stem cell behaviors due to their special mechanical and biological properties and biomimetic characteristics. Therefore, they have been given great attention in tissue regeneration. Nanomaterials are divided into organic and inorganic nanomaterials. They provide the microenvironment to support differentiation of stem cells. Nanomaterials inducing stem cells to differentiate into chondrocyte phenotypes would be a benefit for cartilage tissue regeneration, then promoting the development of cartilage tissue engineering. In this review, we summarized the important roles of nanomaterials in chondrogenic differentiation of stem cells.

Paclitaxel (PTX) is an effective drug against diseases such as lung cancer, ovarian cancer, and breast cancer. However, multidrug resistance limits the clinical applications of this drug. Tetrahedral DNA nanostructures (TDNs) offer great promise as a drug delivery candidate. In our study, we prepared TDNs that were subsequently loaded with PTX (PTX/TDNs). The cytotoxicity of PTX/TDNs and PTX alone on non-small cell lung cancer (NSCLC) cells (A549) and the PTX-resistant cell line (A549/T) was determined using a cell count kit-8 (CCK-8) assay. PTX/TDNs exerted strong lethality on both cell lines. Moreover, drug resistance was overcome. Furthermore, the mechanisms used by PTX/TDNs to overcome drug resistance were studied. The expression of mdr 1 gene and P-glycoprotein (P-gp) in A549/T was found to be downregulated, thus indicating that TDNs serve as a P-gp inhibitor. We also showed that PTX/TDNs killed cancer cells via apoptosis. Thus, PTX/TDNs have great potential for use as a nanodelivery system for the treatment of PTX-resistant NSCLC.

DNA nanorobots have emerged as new tools for nanomedicine with the potential to ameliorate the delivery and anticancer efficacy of various drugs. DNA nanostructures have been considered one of the most promising nanocarriers. In the present study, we report a DNA framework-based intelligent DNA nanorobot for selective lysosomal degradation of tumor-specific proteins on cancer cells. We site-specifically anchored an anti-HER2 aptamer (HApt) on a tetrahedral framework nucleic acid (tFNA). This DNA nanorobot (HApt-tFNA) could target HER2-positive breast cancer cells and specifically induce the lysosomal degradation of the membrane protein HER2. An injection of the DNA nanorobot into a mouse model revealed that the presence of tFNA enhanced the stability and prolonged the blood circulation time of HApt, and HApt-tFNA could therefore drive HER2 into lysosomal degradation with a higher efficiency. The formation of the HER2-HApt-tFNA complexes resulted in the HER2-mediated endocytosis and digestion in lysosomes, which effectively reduced the amount of HER2 on the cell surfaces. An increased HER2 digestion through HApt-tFNA further induced cell apoptosis and arrested cell growth. Hence, this novel DNA nanorobot sheds new light on targeted protein degradation for precision breast cancer therapy.

Objectives Pegaptanib might be a promising anti‐tumour drug targeting VEGF to inhibit tumour vascular endothelial cell proliferation. However, the poor biostability limited its application. In this study, we took tetrahedron DNA nanostructures (TDNs) as drug nanocarrier for pegaptanib to explore the potent anti‐angiogenesis and anti‐tumour activity of this drug delivery system. Materials and methods The successful synthesis of TDNs and pegaptanib‐TDNs was determined by 8% polyacrylamide gel electrophoresis (PAGE), capillary electrophoresis and dynamic light scattering (DLS). The cytotoxicity of pegaptanib alone and pegaptanib‐TDNs on HUVECs and Cal27 was evaluated by the cell count kit‐8 (CCK‐8) assay. The effect of pegaptanib and pegaptanib‐TDNs on proliferation, migration and tube formation of HUVECs induced by VEGF was examined by CCK‐8 assay, wound healing assay and tubule formation experiment. The cell binding capacity and serum stability were detected by flow cytometry and PAGE, respectively. Results Pegaptanib‐TDNs had stronger killing ability than pegaptanib alone, and the inhibiting effect was in a concentration‐dependent manner. What's more, pegaptanib‐loaded TDNs could effectively enhance the ability of pegaptanib to inhibit proliferation, migration and tube formation of HUVECs induced by VEGF. These might attribute to the stronger binding affinity to the cell membrane and greater serum stability of pegaptanib‐TDNs. Conclusions These results suggested that pegaptanib‐TDNs might be a novel strategy to improve anti‐angiogenesis and anti‐tumour ability of pegaptanib.

DNA nanotechnology is a new frontier in the field of tumor biotherapy. Simple DNA strands can be precisely constructed for integration into nanostructures of desired shapes and sizes, with excellent stability and biocompatibility. In this review, an account of the wide range of nanostructures composed of DNA sequences and related advances in oncotherapy using aptamers and chemical drugs is given. Functional ligands, including enzymes, antibodies, and agents, have been appended to DNA frameworks based on their external and internal modifiability. Hence, additional functionalities, such as immunogenicity and enzymatic activity, have been obtained, which extend their practical applications. Importantly, aptamers and drugs can be attached to or incorporated into the wireframes, bringing in highly selective targeting and killing abilities for the modified DNA nanostructures (DNs). In conclusion, distinct DNA sequences, various functional molecules, and different interactions and modifications lead to the diversity of DNs. Currently, one of the leading areas is their applications in tumor therapy. But beyond that, DNs should have much wider application prospects.

Cardiovascular diseases are the major cause of mortality in diabetes patients. Increased levels of glycated low density lipoprotein (glyLDL) are detected in diabetic patients. Endothelial nitric oxide synthase (eNOS) generates nitric oxide, which is responsible to endothelium-dependent vasodilation. The impact of glyLDL on the expression and activity of eNOS in vascular endothelial cells (EC) remains unknown. The present study investigated the effect of glyLDL on the levels of protein, mRNA and activity of eNOS in cultured human umbilical vein EC. The results demonstrated that incubation of EC with physiological concentrations of glyLDL significantly reduced the abundances of eNOS protein in EC with the maximal inhibition at 100μg/ml for 24h. At the optimized condition, glyLDL decreased eNOS mRNA and reduced its activity in EC. Blocking antibody against the receptor for advanced glycation end products (RAGE) prevented glyLDL-induced downregulation of eNOS in EC. GlyLDL increased the translocation of H-Ras from cytoplasm to membrane in EC. Farnesyl-transferase inhibitor-276, an H-Ras antagonist, normalized glyLDL-induced downregulation of eNOS and prevented glyLDL-induced upregulation of H-Ras in EC membrane. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress antagonist, prevented glyLDL-induced eNOS downregulation in EC. The results suggest that diabetes-associated metabolic stress inhibits the production and activity of eNOA in cultured human vascular EC through the activation of RAGE/H-Ras mediated upstream signaling pathway. ER stress induced by glyLDL is possibly involved in eNOS downregulation.

Background Brain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD). Aims To explore the diagnostic value of the measurement of blood thiamine metabolites for AD. Methods Blood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable γ that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients. Results TDP and the γ exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The γ had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the γ can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for γ) and frontotemporal dementia (84.6% for TDP, 100.0% for γ). Interpretation. The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits., Highlights • The measurement of blood thiamine metabolites by HPLC as a promising biomarker test for Alzheimer’s disease diagnosis. • This test is inexpensive, easy to perform and noninvasive which meets the criteria of ideal biomarker for Alzheimer’s disease. The disturbance of brain glucose metabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate, one of thiamine metabolites, is a critical coenzyme for three key enzymes of glucose metabolism and significantly reduced in brain and blood samples of a small number of Alzheimer's disease patients. Our study demonstrates that the measurement of blood thiamine metabolites, manifested as thiamine diphosphate level and the variable γ representing the best combination of thiamine metabolites and age, exhibits excellent value for Alzheimer's disease diagnosis with inexpensive, easy to perform, noninvasive merits.

Endoplasmic reticulum (ER) stress is associated with insulin resistance and diabetic cardiovascular complications, and mechanism or remedy for ER stress remains to be determined. The results of the present study demonstrated that the levels of ER stress or unfolded protein response (UPR) markers, the intensity of thioflavin T (ThT) fluorescence and the abundances of GRP78/94, XBP-1 and CHOP proteins were elevated in cardiovascular tissue of diabetic leptin receptor-deficient (db/db) mice. Cyanidin-3-glucoside (C3G) and cyanidin-3-galactoside (C3Ga) are major anthocyanins in Saskatoon berry (SB) powder. The administration of 5% SB powder for 4 weeks attenuated ThT fluorescence and the UPR markers in hearts and aortae of wild-type and db/db mice. Treatment with glycated low-density lipoprotein (gLDL) increased ThT intensity in human umbilical vein endothelial cells (ECs). Elevated UPR markers were detected in gLDL-treated EC compared to control cultures. The involvement of ER stress in gLDL-treated EC was supported by that the addition of 4-phenyl butyrate acid (a known ER stress antagonist) inhibited gLDL-induced increases in ER stress or UPR markers. C3G at 30 μM or C3Ga at 100 μM reached their maximal inhibition on gLDL-induced increases in ThT, GRP78/94, XBP-1 and CHOP in EC. The results demonstrated that ER stress was enhanced in cardiovascular tissue of db/db mice or gLDL-treated EC. SB powder or cyanidin glycans prevented the abnormal increases in ER stress and UPR markers in cardiovascular tissue of diabetic db/db mice or gLDL-treated EC.

Tetrahedral DNA nanostructures (TDNs) are considered promising drug delivery carriers because they are able to permeate cellular membrane and are biocompatible and biodegradable. Furthermore, they can be modified by functional groups. To improve the drug-delivering ability of TDNs, we chose anticancer aptamer AS1411 to modify TDNs for tumor-targeted drug delivery. AS1411 can specifically bind to nucleolin, which is overexpressed on the cell membrane of tumor cells. Furthermore, AS1411 can inhibit NF-κB signaling and reduce the expression of bcl-2. In this study, we compared the intracellular localization of AS1411-modified TDNs (Apt-TDNs) with that of TDNs in different cells under hypoxic condition. Furthermore, we compared the effects of Apt-TDNs and TDNs on cell growth and cell cycle under hypoxic condition. A substantial amount of Apt-TDNs entered and accumulated in the nucleus of MCF-7 cells; however, the amount of Apt-TDNs that entered L929 cells was comparatively less. TDNs entered in much lower quantity in MCF-7 cells than Apt-TDNs. Moreover, there was little difference in the amount of TDNs that entered L929 cells and MCF-7 cells. Apt-TDNs can inhibit MCF-7 cell growth and promote L929 cell growth, while TDNs can promote both MCF-7 and L929 cell growth. Thus, the results indicate that Apt-TDNs are more effective tumor-targeted drug delivery vehicles than TDNs, with the ability to specifically inhibit tumor cell growth.

Hepatitis B virus (HBV) infection may cause acute hepatitis B, chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV evades host immunity and maintains chronic infection are largely unknown. Here, we revealed that matrix metalloproteinase 9 (MMP-9) is activated in peripheral blood mononuclear cells (PBMCs) of HBV-infected patients, and HBV stimulates MMP-9 expression in macrophages and PBMCs isolated from healthy individuals. MMP-9 plays important roles in the breakdown of the extracellular matrix and in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. MMP-9 also regulates respiratory syncytial virus (RSV) replication, but the mechanism underlying such regulation is unknown. We further demonstrated that MMP-9 facilitates HBV replication by repressing the interferon (IFN)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, IFN action, STAT1/2 phosphorylation, and IFN-stimulated gene (ISG) expression. Moreover, MMP-9 binds to type I IFN receptor 1 (IFNAR1) and facilitates IFNAR1 phosphorylation, ubiquitination, subcellular distribution, and degradation to interfere with the binding of IFANR1 to IFN-α. Thus, we identified a novel positive-feedback regulation loop between HBV replication and MMP-9 production. On one hand, HBV activates MMP-9 in infected patients and leukocytes. On the other hand, MMP-9 facilitates HBV replication through repressing IFN/JAK/STAT signaling, IFNAR1 function, and IFN-α action. Therefore, HBV may take the advantage of MMP-9 function to establish or maintain chronic infection. IMPORTANCE Hepatitis B virus (HBV) infection may cause chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV maintains chronic infection are largely unknown. Matrix metalloproteinase 9 (MMP-9) plays important roles in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. However, the effects of MMP-9 on HBV replication and pathogenesis are not known. This study reveals that MMP-9 expression is activated in patients with CHB, and HBV stimulates MMP-9 production in PBMCs and macrophages. More interestingly, MMP-9 in turn promotes HBV replication through suppressing IFN-α action. Moreover, MMP-9 interacts with type I interferon receptor 1 (IFNAR1) to disturb the binding of IFN-α to IFNAR1 and facilitate the phosphorylation, ubiquitination, subcellular distribution, and degradation of IFNAR1. Therefore, these results discover a novel role of MMP-9 in viral replication and reveal a new mechanism by which HBV evades host immunity to maintain persistent infection.

Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombogenesis, inflammation, and extracellular matrix remodeling. Previous studies indicated that oxidized low-density lipoprotein (LDL) stimulated the generation of PAI-1 in vascular endothelial cells (EC). The present study demonstrated that LDL oxidized by copper, iron, or 3-morpholinosydnonimine increased the expression of NADPH oxidase (NOX) 2, PAI-1, and heat shock factor-1 (HSF1) in human umbilical vein EC or coronary artery EC compared with LDL or vehicle. Diphenyleneiodonium, a NOX inhibitor, prevented the increases of the expression of HSF1 and PAI-1 in EC induced by oxidized LDLs. Small-interference RNA (siRNA) for p22phox, an essential subunit of NOX, prevented oxidized LDL-induced expression of NOX2, HSF1, and PAI-1 in EC. HSF1 siRNA inhibited oxidized LDL-induced expression of PAI-1 and HSF1, but not NOX2, in EC. The binding of HSF1 to PAI-1 promoter and the activity of PAI-1 promoter in EC were enhanced by oxidized LDL. Butylated hydroxytulene, a potent antioxidant, inhibited oxidized LDL-induced release of hydrogen peroxide (H2O2) and the expression of NOX2, HSF1, and PAI-1 in EC. Treatment with H2O2 increased the abundance of NOX2, HSF1, and PAI-1 in EC. The results of the present study indicate that oxidized LDL-induced expression of NOX may lead to the elevated release of reactive oxygen species, the activation of HSF1, and the enhancement of the transcription of PAI-1 gene in cultured vascular EC.

Hepatitis B virus (HBV) infection is a major cause of liver diseases. However, the mechanisms underlying HBV infection and pathogenesis remain largely unknown. The sex-determining region Y box 4 (Sox4) is a transcriptional factor, which preferentially regulates the development of various organs, tissues and cancers. But, the role of Sox4 in viral infection and pathogenesis has not been elucidated. Here, we demonstrated that Sox4 is up-regulated by HBV and revealed the mechanism by which HBV regulates Sox4 expression. First, HBV stimulates Sox4 expression through transcriptional factor Yin Yang 1 (YY1), which binds to Sox4 promoter to activate Sox4 transcriptional activity. Second, miR-335, miR-129-2 and miR-203 inhibit Sox4 expression by targeting its mRNA 3’UTR, while HBV suppresses the microRNAs expression, resulting in up-regulating Sox4 post-transcriptionally. Third, Sox4 protein is degraded by proteasome, while HBV surface protein (HBsAg) prevents Sox4 from degradation by directly interacting with the protein, thereby enhancing Sox4 production post-translationlly. More interestingly, HBV-activated Sox4 in turn facilitates HBV replication by direct binding to the viral genome via its HMG box. Thus, this study revealed a novel positive feedback mechanism by which Sox4 production and HBV replication are tightly correlated.

Impairments in mitochondrial function have been proposed to play an important role in the pathogenesis of diabetes. Atherosclerotic coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Mitochondrial dysfunction and increased production of reactive oxygen species (ROS) are associated with diabetes and CAD. Elevated levels of glycated low density lipoproteins (glyLDL) and oxidized LDL (oxLDL) were detected in patients with diabetes. Our previous studies demonstrated that oxLDL and glyLDL increased the generation of ROS and altered the activities of antioxidant enzymes in vascular endothelial cells (EC). The present study examined the effects of glyLDL and oxLDL on mitochondrial respiration, membrane potential and the activities and proteins of key enzymes in mitochondrial electron transport chain (mETC) in cultured porcine aortic EC (PAEC). The results demonstrated that glyLDL or oxLDL significantly reduced oxygen consumption in Complex I, II/III and IV of mETC in PAEC compared to LDL or vehicle control using oxygraphy. Incubation with glyLDL or oxLDL significantly reduced mitochondrial membrane potential, the activities of mitochondrial ETC enzymes - NADH dehydrogenase (Complex I), succinate cytochrome c reductase (Complex II + III), ubiquinol cytochrome c reductase (Complex III), and cytochrome c oxidase (Complex IV) in PAEC compared to LDL or control. Treatment with oxLDL or glyLDL reduced the abundance of subunits of Complex I, ND1 and ND6 in PAEC. However, the effects of oxLDL on mitochondrial activity and proteins were not significantly different from glyLDL. The findings suggest that the glyLDL or oxLDL impairs mitochondrial respiration, as a result from the reduction of the abundance of several key enzymes in mitochondria of vascular EC, which potentially may lead to oxidative stress in vascular EC, and the development of diabetic vascular complications.