Bee Bread Can Alleviate Lipid Abnormalities and Impaired Bone Morphology in Obese Zucker Diabetic Rats

This study examined for the first time whether bee bread (BB, consisting of monofloral rape bee pollen) could alleviate lipid derangements and reduced bone quality in Zucker diabetic fatty (ZDF) rats, which are considered an appropriate animal model for type 2 diabetes mellitus (T2DM) investigation. Adult ZDF rats were segregated into four groups: lean non-diabetic rats (L group), obese diabetic rats untreated (C group), and those treated with the BB at two doses (500 and 700 mg/kg body weight, respectively, B1 and B2 groups) for 10 weeks. Significantly reduced levels of total cholesterol and triglyceride were recorded in the B2 group versus the C group. In both BB-treated groups, significantly increased relative volume of trabecular bone and trabecular thickness, enhanced density of secondary osteons, accelerated periosteal bone apposition, and improved blood flow were observed. A positive effect of higher dose of BB on femoral weight and cortical bone thickness was also demonstrated. Our results suggest a promising potential of BB to ameliorate T2DM-related complications associated with lipid and bone damages.     

Impaired erythrocyte transmembrane potential in diabetes mellitus and its possible improvement by resorcylidene aminoguanidine

Erythrocytes of diabetic patients have abnormal membrane properties. We examined in vitro transmembrane potential and the possible effect of resorcylidene aminoguanidine (RAG) on its modulation in erythrocytes of diabetic subjects. The transmembrane potential was assessed in RAG-treated and untreated erythrocytes, respectively, using a fluorescent dye (3,3'-dipropylthiadicarbocyanine iodide [DiSC3(5)]). We confirmed earlier findings that the transmembrane potential of diabetic erythrocytes is significantly increased compared with control (P < 0.01). The membrane hyperpolarization found in diabetic cells seems to be a result of oxidative stress present in diabetes mellitus. On one hand, the RAG treatment induced decrease in abnormal transmembrane potential values in diabetic erythrocytes (P < 0.01), presumably via its antioxidant and antiglycation activity. On the other hand, RAG moderately hyperpolarized the control erythrocytes (P < 0.05). We suggest that the drug-induced transient membrane expansion leads to an intracellular potassium loss and a subsequent change of the transmembrane potential. However, if controlled by an appropriate dosage, RAG can eliminate certain types of erythrocyte membrane damage induced by diabetes mellitus.     

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.     

Metabolite Variation in Lean and Obese Streptozotocin (STZ)-Induced Diabetic Rats via <Superscript>1</Superscript>H NMR-Based Metabolomics Approach

Diabetes mellitus (DM) is considered as a complex metabolic disease because it affects the metabolism of glucose and other metabolites. Although many diabetes studies have been conducted in animal models throughout the years, the pathogenesis of this disease, especially between lean diabetes (ND + STZ) and obese diabetes (OB + STZ), is still not fully understood. In this study, the urine from ND + STZ, OB + STZ, lean/control (ND), and OB + STZ rats were collected and compared by using ¹H NMR metabolomics. The results from multivariate data analysis (MVDA) showed that the diabetic groups (ND + STZ and OB + STZ) have similarities and dissimilarities for a certain level of metabolites. Differences between ND + STZ and OB + STZ were particularly noticeable in the synthesis of ketone bodies, branched-chain amino acid (BCAA), and sensitivity towards the oral T2DM diabetes drug metformin. This finding suggests that the ND + STZ group was more similar to the T1DM model and OB + STZ to the T2DM model. In addition, we also managed to identify several pathways and metabolism aspects shared by obese (OB) and OB + STZ. The results from this study are useful in developing drug target-based research as they can increase understanding regarding the cause and effect of DM.     

A comparative study of 632.8 and 532 nm laser irradiation on some rheological factors in human blood in vitro

The effects of laser irradiation with 632.8 and 532 nm on rheological properties of blood were comparatively studied in vitro. Under the irradiation condition of 30 mW, laser irradiation of blood samples using a spot diameter of 5 mm with each laser, showed promising results in the modulation of hemorheological properties. When blood samples from patients with abnormally high values of erythrocyte sedimentation rate (ESR) were irradiated, the values of ESR were lowered statistically by either of the 632.8 or 532 nm lasers. The laser irradiation reduced blood viscosities at different shear rates (10-110 S(-1)) for the hyper-viscosity blood samples. Laser irradiation increased the electrophoretic mobility (EPM) of erythrocytes when the values of the sample's EPM were abnormally slow. The erythrocyte deformability was enhanced by laser irradiation when the deformability of the sample from the patients was originally poor. For verifying the improvement of laser irradiation on erythrocyte deformability, the typical erythrocyte samples with poor deformability were produced by the pre-treatment of the erythrocytes with Ca(2+). The deformability of these erythrocyte samples was also improved after laser irradiation. These results suggest that membrane-bound hemoglobin (Hbm) might be the initial site of the interaction, since Hbm is the main cause of poor deformability when erythrocytes were treated with Ca(2+). In all experiments including ESR, blood viscosity, EPM and erythrocyte deformability, the 532 nm laser demonstrated more efficient effects on modulating rheological properties than 632.8 nm laser. This wavelength effect is consistent with the absorption spectrum of hemoglobin, reflecting that hemoglobin may be one of the action targets under laser irradiation.     

The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry

Analysis of biological fluids using ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) (metabonomics) can allow new insights to be gained into disease processes, with advances in chromatographic techniques enabling the detection of thousands of metabolites. In this work metabonomics has been used to investigate the metabolic processes involved in type II diabetes in the Zucker obese rat. Plasma was analyzed from three different strains, the Zucker (fa/fa) obese, Zucker lean and the lean/(fa) obese cross. Using UPLC/MS, ca. 10,000 ions were detected due to the narrow peak widths and excellent peak shapes achieved with this technology. Confidence in the chromatographic performance was demonstrated by the use of quality control standards. The positive and negative ion total ion chromatograms obtained from the three strains were readily distinguishable using multivariate statistical analysis. The greatest difference was observed between the Zucker lean and Zucker lean/(fa) rats compared to the Zucker (fa/fa) obese rats. Positive ions m/z 220 (4.36 min), 282(3.78 min), 359 (5.33 min) and 405 (7.77 min) were elevated in the plasma derived from Zucker lean rats whilst ions m/z 385 (6.80 min) and 646 (4.36 min) were at a lower concentration compared to the plasma from the Zucker (fa/fa) obese animals. Negative ions elevated in the Zucker lean rats included m/z 212 (2.30 min), 514 (2.85 min), 295 (4.39 min), 329 (3.11 min), 343 (2.86 min) and 512 (2.86 min) with ions m/z 538 (4.18 min), 568 (4.18 min), 568 (5.09 min) and 612 (4.30 min) being raised in the samples derived from Zucker (fa/fa) obese animals. The ion m/z 514 (3.85 min) was found to correspond to taurocholate, providing further support for an involvement of taurine metabolism in diabetes.     

Effect of low power laser irradiation on disconnecting the membrane-attached hemoglobin from erythrocyte membrane

In our previous study we found that low power laser irradiation improved the erythrocyte deformability, but the mechanism is unclear. The membrane-attached hemoglobin (Hbm) may be one of the determining factors for the erythrocyte deformability. We report here for the first time, that laser irradiation can reduce the Hbm contents in pig's erythrocytes, providing the explanation for the improvement of erythrocyte deformability. The decrease of the Hbm was proportional to the irradiation dose, but the relative change of Hbm was saturated around 35%. The 532 nm laser was more efficient at lowering Hbm than the 632.8 nm laser, consistent with the absorption spectrum of Hbm.     

Na-nitroprusside and HgCl2 modify the water permeability and volume of human erythrocytes

The passage of water through the aquaporin-1 (AQP1) transmembrane channel protein of the human erythrocyte is known to be inhibited by organic mercurials such as p-chloromercuribenzoate (pCMB), which react with the free SH-group of the critical cysteine (Cys189) located near the constriction of the AQP1 water-specific channel. Sodium nitroprusside (SNP), which is known as a nitric oxide (NO) donor in interactions with SH-containing molecules, is shown here to suppress the diffusional water permeability (P(d)) of the erythrocyte membrane, presumably as a result of reaction with the Cys189 of the human erythrocyte AQP1 water channels. Further, treatment of erythrocytes with HgCl(2) is found to result in a cell volume decrease that can be related to activation of membrane K(+)-selective Gárdos channels and subsequent loss of intracellular K(+) and cell shrinkage. The variations in P(d) and volume of the erythrocyte were deduced from induced variations in the measured proton ((1)H) nuclear magnetic resonance (NMR) transverse (T(2)) relaxation functions of water exchanging between diamagnetic intracellular and paramagnetic extracellular compartments of the 20-25% hematocrit samples. The extracellular solvent contained 10 mM membrane-impermeable paramagnetic Mn(2+) ions. The (1)H-T(2) NMR technique allows determination of the time constant tau(exch) (for exchange of the erythrocyte intracellular water) that is inversely proportional to the permeability coefficient P(d) when the intracellular water volume is left unmodified, as in the case of SNP-treated erythrocytes. However, for HgCl(2)-treated erythrocytes, this technique showed simultaneous variation of both tau(exch) and the volume ratio V(in)/V(out) of intracellular and extracellular water in proportions suggesting that P(d) was left unmodified. The HgCl(2) effect has been found to be partly reversible by the reducing activity of added mercaptoethanol.     

Antidiabetic Activity of Ethanolic Extract of Zaleya decandra in Alloxan-Induced Diabetic Rats

Diabetes mellitus is a complex disorder that disturbs the metabolism of carbohydrates, fats, and proteins. Medicinal plants play an important role in the management of diabetes mellitus. The present study was aimed to evaluate the antidiabetic potential of Zaleya decandra roots on alloxan-induced diabetes in rats. Oral administration of ethanolic extract of the root (200 mg/kg body weight/day) for 15 days restored the levels of glucose, cholesterol, triglycerides, total proteins, urea, creatinine, lipid peroxidation level, and antioxidant enzymes significantly in diabetic rats. Histopathological studies showed significant changes like necrosis and degeneration in the liver and pancreas of alloxan-induced diabetic rats. Also these histopathological abnormalities were found to be normalized after treatment with Z. decandra extract. The efficacy of the root extract was found to be equivalent when compared to the standard hypoglycemic drug glibenclamide (1.25 mg/kg body weight/day, orally) in diabetic rats.     

A metabonomic analysis of plasma from Zucker rat strains using gas chromatography/mass spectrometry and pattern recognition

Plasma obtained from three strains of Zucker rats was analysed using capillary gas chromatography/mass spectrometry (GC/MS) to obtain global metabolite profiles as part of a series of metabonomic investigations of animal models of diabetes. Samples were obtained from 20-week-old male wild-type Zucker lean, (fa/fa) obese and lean/(fa) animals and were analysed following protein precipitation, using acetonitrile, and derivatisation. Subsequent data analysis using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) revealed differences between the plasma metabolite profiles of the three strains, with those of the Zucker lean and the lean/(fa) crosses being similar to each other whilst differing from the (fa/fa) obese strain.     

糖肾方对自发性Ⅱ型糖尿病鼠磷脂代谢的影响

利用正相液相色谱飞行时间质谱建立了大鼠血浆磷脂的轮廓谱。通过对磷脂轮廓谱的PLS-DA判别分析及14种化合物的定量,考察了中药糖肾方对自发性II型糖尿病鼠磷脂代谢的影响,并对比了糖肾方与西药蒙诺在糖尿病发展过程中的不同作用。结果表明：与正常对照组相比,糖尿病鼠的血浆磷脂代谢发生异常。糖肾方能够调节糖尿病鼠的磷脂代谢紊乱,蒙诺则加剧了病鼠的磷脂代谢异常。此外,8种磷脂化合物可能成为糖尿病发展过程中的潜在生物标志物。     

Gold nanoparticles as carriers for efficient transmucosal insulin delivery

Nanomaterials have gained tremendous importance in biology and medicine because they can be used as carriers for delivering small molecules such as drugs, proteins, and genes. We report herein the binding of the hormone insulin to gold nanoparticles and its application in transmucosal delivery for the therapeutic treatment of diabetes mellitus. Insulin was loaded onto bare gold nanoparticles and aspartic acid-capped gold nanoparticles and delivered in diabetic Wistar rats by both oral and intranasal (transmucosal) routes. Our principle observations are that there is a significant reduction of blood glucose levels (postprandial hyperglycemia) when insulin is delivered using gold nanoparticles as carriers by the transmucosal route in diabetic rats. Furthermore, control of postprandial hyperglycemia by the intranasal delivery protocol is comparable to that achieved using the standard subcutaneous administration used for type I diabetes mellitus, thus showing considerable promise for further development.     

Cell Adhesion onto Highly Curved Surfaces: One‐Step Immobilization of Human Erythrocyte Membranes on Silica Beads

This paper deals with single‐step, orientation‐selective immobilization of human erythrocyte membranes on bare silica beads with different topographies: 1) solid (nonporous) silica beads with a diameter of 3 μm and 2) porous silica beads with a diameter of 5 μm. Erythrocyte membranes were immobilized onto beads simply by incubation, without sonication or osmotic lysis. Membrane orientation before and after immobilization was identified with two immunofluorescence labels: 1) the extracellular part of glycophorin can be labeled with a first monoclonal antibody and a second polyclonal antibody with fluorescence dyes (outside label), while 2) the cytoplasmic domain of Band 3 can be recognized with a first monoclonal antibody and a second fluorescent polyclonal antibody (inside label). Adherent erythrocytes on the beads all ruptured, inverted the asymmetric orientation of the membrane, and selectively exposed their cytoplasmic domain. The surface topography did not influence the orientation or the amount of immobilized membrane. On the other hand, the fact that no adsorption or rupture of erythrocytes could be observed on planar quartz substrates suggests a significant influence of contact curvature on adhesion energy.     

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), urea, and creatinine increased significantly in the DPN and diabetic rats without peripheral neuropathy (PN) compared with control group. The treatment of DNP with gabapentin induced significant increases in ALAT and ASAT activities but LLLT treatment induced significant decreases in ALAT and ASAT activities as compared with DNP group. Neither gabapentin nor LLLT could improve the elevated levels of serum urea and creatinine in the DNP. It could be concluded that LLLT is more safe and effective than gabapentin in the management of neuropathy in diabetic rats.     

The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.     

Protective effects of Ocimum sanctum on lipid peroxidation and antioxidant status in streptozocin-induced diabetic rats

The antioxidant effects of Ocimum sanctum in experimental streptozocin-induced diabetic rats was evaluated in this study. Streptozocin, 55?mg?kg(-1) body weight, was injected intraperitoneally once daily for 30 days to induce diabetes mellitus in rats. Streptozocin-induced diabetic rats were orally treated with an aqueous extract of O. sanctum once daily for 30 days. After the experimental period, thiobarbituric acid reacting substances (TBARS) and antioxidant enzymes such as catalase, superoxide dismutase (SOD) and glutathione peroxidase were measured. Administration of O. sanctum to streptozocin-induced diabetic rats for 30 days significantly reduced the plasma level of TBARS and improved the status of the antioxidant enzymes catalase, SOD and glutathione peroxidase in vital organs such as the liver and kidney. These results confirmed that the Indian medicinal plant O. sanctum has a protective effect and it may be useful in controlling complications resulting from diabetes.     

The Effects of Streptozotocin-Induced Diabetes and Insulin Treatment on Carnitine Biosynthesis and Renal Excretion

Carnitine insufficiency is reported in type 1 diabetes mellitus. To determine whether this is accompanied by defects in biosynthesis and/or renal uptake, liver and kidney were obtained from male Sprague-Dawley rats with streptozotocin-induced diabetes. Diabetic rats exhibited the metabolic consequences of type 1 diabetes, including hypoinsulinemia, hyperglycemia, and increased urine output. Systemic hypocarnitinemia, expressed as free carnitine levels, was evident in the plasma, liver, and kidney of diabetic rats. Compared to control rats, the low free carnitine in the plasma of diabetic rats was accompanied by decreased expression of γ-butyrobetaine hydroxylase in liver and kidney, suggesting impaired carnitine biosynthesis. Expression of organic cation transporter-2 in kidney was also reduced, indicating impaired renal reabsorption, and confirmed by the presence of elevated levels of free carnitine in the urine of diabetic rats. Insulin treatment of diabetic rats reversed the plasma hypocarnitinemia, increased the free carnitine content in both kidney and liver, and prevented urinary losses of free carnitine. This was associated with increased expression of γ-butyrobetaine hydroxylase and organic cation transporter-2. The results of our study indicate that type 1 diabetes induced with streptozotocin disrupts carnitine biosynthesis and renal uptake mechanisms, leading to carnitine insufficiency. These aberrations in carnitine homeostasis are prevented with daily insulin treatment.     

基于气相色谱-质谱联用的代谢组学用于黄连治疗II型糖尿病的机理探索

将代谢组学的方法用于研究黄连治疗II型糖尿病的机理。II型糖尿病造模采用对大鼠灌胃脂肪乳并腹腔注射40 mg/kg链脲佐菌素的方法,大鼠分为正常组、模型组、黄连给药治疗组(10 g/kg)、二甲双胍给药治疗组(0.08 g/kg)。大鼠给药30天后,采集血样用于生化指标的检测,采集24 h尿样用于代谢组学的分析。与模型组相比,糖尿病大鼠给药黄连30天后,空腹血糖值(FBG)显著降低了59.26%,总胆固醇(TC)降低了58.66%,甘油三酯(TG)降低了42.18%。采用气相色谱-质谱联用技术(GC-MS)对大鼠尿样中的内源性物质进行了相对含量测定,主成分分析结果表明,正常组与模型组显著分离,黄连组处于正常组与模型组之间,更接近于正常组。发现12个代谢物与糖尿病有关,包括4-甲基苯酚、苯甲酸、氨基丙二酸等。给药黄连后,其中的7个代谢物发生显著性回调,与氧化应激状态相关的氨基丙二酸和L-抗坏血酸出现向正常组显著性调节的趋势。这些结果表明,黄连不仅具有降糖和降血脂的作用,而且具有抗氧化作用,在一定程度上可能会抑制糖尿病合并症的发生和发展。     

Accumulation of argpyrimidine, a methylglyoxal-derived advanced glycation end product, increases apoptosis of lens epithelial cells both in vitro and in vivo

The formation of advanced glycation end products (AGEs) has been considered to be a potential causative factor of injury to lens epithelial cells (LECs). Damage of LECs is believed to contribute to cataract formation. The purpose of this study was to investigate the cytotoxic effect of AGEs on LECs both in vitro and in vivo. We examined the accumulation of argpyrimidine, a methylglyoxal-derived AGE, and the expression of apoptosis-related molecules including nuclear factor- kappaB (NF-κB), Bax, and Bcl-2 in the human LEC line HLE-B3 and in cataractous lenses of Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. In cataractous lenses from twenty-oneweek- old ZDF rats, LEC apoptosis was markedly increased, and the accumulation of argpyrimidine as well as subsequent activation of NF-κB in LECs were significantly enhanced. The ratio of Bax to Bcl-2 protein levels was also increased. In addition, the accumulation of argpyrimidine triggered apoptosis in methylglyoxal- treated HLE-B3 cells. However, the presence of pyridoxamine (an AGEs inhibitor) and pyrrolidine dithiocarbamate (a NF-κB inhibitor) prevented apoptosis in HLE-B3 cells through the inhibition of argpyrimidine formation and the blockage of NF-κB nuclear translocalization, respectively. These results suggest that the cellular accumulation of argpyrimidine in LECs is NF-κB-dependent and pro-apoptotic.