mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.

BACKGROUND: Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear. METHODS: Brain EC-specific CCM3-deficient (Pdcd10BECKO) mice were generated by crossing Pdcd10fl/fl mice with Mfsd2a-CreERT2 mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches. RESULTS: Single-cell RNA-sequencing analyses from P10 Pdcd10BECKO mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 Pdcd10BECKO brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the Pdcd10BECKO model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in Pdcd10BECKO mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins. CONCLUSIONS: CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.

The Effect of Irradiation on Meat Products.

The effects of irradiation on meat constituents including water, proteins, and lipids are multifaceted. Irradiation leads to the decomposition of water molecules, resulting in the formation of free radicals that can have both positive and negative effects on meat quality and storage. Although irradiation reduces the number of microorganisms and extends the shelf life of meat by damaging microbial DNA and cell membranes, it can also accelerate the oxidation of lipids and proteins, particularly sulfur-containing amino acids and unsaturated fatty acids. With regard to proteins, irradiation affects both myofibrillar and sarcoplasmic proteins. Myofibrillar proteins, such as actin and myosin, can undergo depolymerization and fragmentation, thereby altering protein solubility and structure. Sarcoplasmic proteins, including myoglobin, undergo structural changes that can alter meat color. Collagen, which is crucial for meat toughness, can undergo an increase in solubility owing to irradiation-induced degradation. The lipid content and composition are also influenced by irradiation, with unsaturated fatty acids being particularly vulnerable to oxidation. This process can lead to changes in the lipid quality and the production of off-odors. However, the effects of irradiation on lipid oxidation may vary depending on factors such as irradiation dose and packaging method. In summary, while irradiation can have beneficial effects, such as microbial reduction and shelf-life extension, it can also lead to changes in meat properties that need to be carefully managed to maintain quality and consumer acceptability.

Variation of volatile compounds and sensory profile for Protaetia brevitarsis larvae fermented with lactic acid bacteria and yeast.

This study aimed to investigate the correlation between the composition of volatile compounds, consumer acceptance, and drivers of (dis)liking of Protaetia brevitarsis larvae fermented using lactic acid bacteria and yeast. Volatile compounds were analyzed using HS-SPME-Arrow-GC-MS, and a sensory evaluation was conducted with 72 consumers. A total of 113 volatile compounds were detected, and principal component analysis indicated that the samples could be divided into three groups. The calculated relative odor activity values (ROAV) revealed the presence of 27 compounds (ROAV >1). Volatile compounds with high ROAV were predominantly found during yeast fermentation. The sensory evaluation results indicated a strong correlation between low levels of off-odor intensity and high odor liking, emphasizing that odor profile had a more direct association with consumer acceptance than odor intensity. These findings suggest that yeast fermentation using volatile compounds, which positively influences consumer acceptance, is appropriate for Protaetia brevitarsis larvae.

Effects of myofibril-palatinose conjugate as a phosphate substitute on meat emulsion quality.

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

Heat-induced gelation of egg white proteins depending on heating temperature: Insights into protein structure and digestive behaviors in the elderly in vitro digestion model.

This study investigated the effects of heating temperature of egg white gels (EWGs) on the digestive characteristics by heating egg white (EW) to reach 75 °C (EWG-75) and 95 °C (EWG-95). The gel protein structure showed a decrease in the maximum tryptophan fluorescence intensity and a significant increase in the surface hydrophobicity of EWGs compared to EW (P < 0.05). The total and reactive free sulfhydryl groups were higher in the EWGs than in the EW (P < 0.05). While the proportions of α-helical and ß-sheet structures remained similar in EW and EWG-75 (P > 0.05), EWG-95 exhibited a notable decrease in α-helix content (P < 0.05) and an increase in ß-sheet content (P < 0.05). Furthermore, EWG-95 displayed higher hardness and cohesiveness than EWG-75 (P < 0.05). In the adult and elderly in vitro digestion models, EWG-95 exhibited the highest protein digestibility (50.44 % and 54.65 % in the models of elderly and adult subjects, respectively) after GI digestion (P < 0.05), followed by EWG-75 and EW. The electrophoretogram of the digesta revealed more intense protein bands in the elderly digestion model, particularly in the gastric digesta of EW, indicating slower digestion compared to the adult model. Therefore, EW should be appropriately heated before consumption, especially for elderly individuals, to facilitate efficient protein digestion and absorption.

Effects of Natural Extract Mixtures on the Quality Characteristics of Sausages during Refrigerated Storage.

Owing to the residual toxicity and adverse health effects of chemical preservatives, there is an increasing demand for using natural preservatives in food. Although many natural extracts have been evaluated, research on their antibacterial effects remains insufficient. Therefore, this study aimed to explore the possibility of developing Psidium guajava, Ecklonia cava, and Paeonia japonica (Makino) Miyabe & Takeda extracts as natural food preservatives. Further, the effect of mixing these extracts on microbial growth and quality was evaluated during the refrigeration of sausages. Optimal mixing ratios were determined based on the minimum inhibitory and bactericidal concentrations of each mixed extract against the Listeria monocytogenes, Salmonella spp. and Escherichia coli. D-optimal mixing design optimization tool was further used to obtain an optimum mixing ratio of Formulation 1 (F1). The antibacterial activity of F1 increased with increasing concentration, with similar activities at 0.5% and 1%. The sausages with synthetic or natural preservatives showed significantly lower lipid oxidation than those of the control and grapefruit extract-treated sausages after 4 wk of refrigeration. Total plate counts were observed only in the control and treatment groups stored for 3 wk, and no significant effect of ascorbic acid was observed. Compared to the other samples, sausages with added natural extracts showed the highest overall acceptability scores initially and after 4 wk. Therefore, similar amounts of grapefruit seed and natural extracts had the same effect on microbiological analysis and lipid rancidity during sausage storage. Hence, this mixture can serve as a potential natural preservative in meat products.

Effects of konjac glucomannan as a freeze-denaturation inhibitor or binder on the physiochemical properties of heat-induced gel of freeze-dried duck blood.

During freeze-drying, the degradation or eutectic melting of duck blood proteins can reduce the quality of duck blood gels. However, the interaction between proteins and polysaccharides during drying can improve protein-based gel quality. Therefore, here, we investigated the physicochemical properties of heat-induced gels of freeze-dried duck blood (FDB) and FDB with different proportions of the polysaccharide konjac glucomannan (KG), which serves as a freeze-denaturation inhibitor agent (FDA) or binder (BG). The pH and water-holding capacity (WHC) of FDB + KG gels were higher than those of FDB gel without KG (control). Especially, the WHC increased from 11.00% for control to 55.65% for FDB gel with 1% KG as a BG. Consequently, cooking loss and texture parameters of FDB + KG gels decreased. The hardness of control was 2.14 kg, which significantly reduced to 0.12-0.87 kg with KG addition. The highest carbonyl content was observed in control gel, and the thiobarbituric acid reactive substance content was reduced by the addition of 1% KG as an FDA (T1) or 0.8% KG as an FDA with 0.2% KG as a BG (T2) (p < 0.05). These changes might be induced by the alteration of tertiary structure and thermodynamic stability of gels. In conclusion, 1% KG can be used as an FDA to improve the quality and physicochemical properties of heat-induced gels of FDB. Optimized FDB gels with KG can be used as an innovative food ingredient to fortify nutrition and develop special dietary purposes.

Comparative Evaluation of Polysaccharide Binders on the Quality Characteristics of Plant-Based Patties.

Polysaccharides have been used in the production of plant-based meat analogs to replicate the texture of real meat. However, there has been no study that comprehensively compares the effects of different polysaccharides, and a limited number of polysaccharides have been evaluated. Thus, we aimed to identify the most suitable polysaccharide and concentration for plant-based patties. Plant-based patties were manufactured by blending different concentrations (0%, 1%, and 2%) of six polysaccharides with other ingredients, and the quality characteristics and sensory properties were evaluated. The L* values of plant-based patties reduced during the cooking process resembled the color change of beef patty (BP). In particular, a 2% κ-carrageenan-added patty (Car-2) exhibited the lowest L* value among the plant-based patties, measured at 44.05 (p < 0.05). Texture parameters exhibited high values by adding 2% κ-carrageenan and locust bean gum, which was close to BP. In the sensory evaluation, Car-2 showed higher scores for sensory preferences than other plant-based patties. Based on our data, incorporating 2% κ-carrageenan could offer a feasible way of crafting plant-based meat analogs due to its potential to enhance texture and flavor. Further studies are required to evaluate the suitability of polysaccharides in various types of plant-based meat analogs.

Absolutely Relative: How Education Shapes Voter Turnout in the United States.

Why has voter turnout in the United States not increased proportionally with educational attainment over time? Relative education theories have attempted to answer this question by highlighting how the value of individuals' education may be influenced by the educational levels achieved by others. For instance, individuals may attain a higher level of education compared to previous generations, but the relative value of their education may not improve if society as a whole also achieves higher levels of education. Thus, this increased educational attainment may have little influence on voter turnout. Using a new measure of relative education and incorporating more recent post-2000 data, this research finds that while the relative education model explains the education-turnout relationship prior to 2000, since then individuals with a higher absolute level of education have been more likely to vote, regardless of the relative value of their education. The rise in voter turnout over the past two decades could be attributed to this increase in the absolute level of education.

Inhibitory effect of natural extract mixtures on microbial growth and lipid oxidation of sausages during storage.

Large amounts of additives are used during meat product processing to maintain product quality and shelf life. With the growing interest in healthy foods, natural plant-based additives are being used as alternatives to synthetic additives. In this study, six types of natural extracts with excellent antibacterial activity were selected, and their antibacterial and antioxidant activities against four types of pathogens were evaluated in various combinations. In addition, the pH, color, amount of thiobarbituric acid reactive substances (TBARS), and growth of pathogenic microorganisms were analyzed during the storage of sausages treated with various combinations of these extracts. The natural extract mixtures exhibited different antibacterial activities, depending on the combination. Compared to grapefruit seed extract, a mixture of natural extracts extracted with ethanol (M4) reduced the Escherichia coli content by more than 99.9% after 8 days of storage and slowed the growth of Listeria monocytogenes and Salmonella spp. by more than 80% after 14 days. Compared to untreated (NC) and grapefruit extract (PC)-treated sausages, sausages treated with the natural extract mixtures showed a significant decrease in CIE L* and an increase in CIE a* and CIE b* (p < 0.05). The pH value was significantly lower in sausages containing natural extract mixtures than in the NC and PC sausages (p < 0.05). The natural plant extract mixtures significantly prevented lipid oxidation (p < 0.05). In summary, different types of natural extract mixtures have a synergistic effect when used together, suggesting that natural preservatives can generally inhibit the growth of microorganisms and oxidation of processed meat.

The Effect of Gelatin Coating and Sonication on the Quality Properties of Wet-Aging Pork Loins.

In this study, we evaluate the effect of gelatin coating and sonication of wet-aged pork loin on quality. The moisture content of wet-aged pork loin with sonication and gelatin coating was the highest in the G5S sample (5% gelatin coating and sonication), while the moisture content of wet-aged pork loin with sonication was higher than that without sonication. The pH of wet-aged pork loin with sonication was lower than that without sonication. The aging loss of 5% gelatin coating with sonication was significantly lower than that of G0 (control), while the cooking loss was the lowest in G0 wet-aged pork loin. The water holding capacity of the wet-aged pork loin was the highest in G1. The thiobarbituric acid reactive substances value of wet-aged pork loin was significantly decreased with coating and not affected by sonication. The gelatin coating and sonication treatment significantly increased the myofibrillar fragmentation index of the samples. Shear force of wet-aged pork loin significantly decreased as the samples were gelatin-coated and sonicated. The myofibrillar and total protein solubilities were not significantly different between samples. In conclusion, the 1% gelatin coating with sonication can enhance the quality of wet-aged pork loin.

The Function of Memory CD8+ T Cells in Immunotherapy for Human Diseases.

Memory T (Tm) cells protect against Ags that they have previously contacted with a fast and robust response. Therefore, developing long-lived Tm cells is a prime goal for many vaccines and therapies to treat human diseases. The remarkable characteristics of Tm cells have led scientists and clinicians to devise methods to make Tm cells more useful. Recently, Tm cells have been highlighted for their role in coronavirus disease 2019 vaccines during the ongoing global pandemic. The importance of Tm cells in cancer has been emerging. However, the precise characteristics and functions of Tm cells in these diseases are not completely understood. In this review, we summarize the known characteristics of Tm cells and their implications in the development of vaccines and immunotherapies for human diseases. In addition, we propose to exploit the beneficial characteristics of Tm cells to develop strategies for effective vaccines and overcome the obstacles of immunotherapy.

Effects of grafted myofibrillar protein as a phosphate replacer in brined pork loin.

For the development of healthier meat products, the grafted myofibrillar protein was evaluated as an ingredient that can substitute phosphate in brined loin. Individual brine solutions, consisting of salt (negative control, NP), salt + sodium tripolyphosphate (positive control, PC), salt + myofibrillar protein without grafting (MP), salt + myofibrillar protein grafted at high concentration (GMP-H), and salt + myofibrillar protein grafted at low concentration (GMP-L), were added to the pork loin by 40% of their weight. Differential scanning calorimetry demonstrated that MP and GMP-H lowered the thermal energy for the transition of myosin and actin, thereby improving the thermal stability of pork loin and increasing protein solubility. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that thicker protein bands appeared in MP and GMP-H samples while exhibiting increased pH values, moisture content, water holding capacity, and processing yield. Accordingly, the shear force of MP and GMP-H decreased. Lipid oxidation of pork loin was increased in MP, whereas it decreased in GMP-H. Thus, GMP-L is a potential substitute for phosphate since it improves physicochemical properties and prevents the lipid oxidation of pork loin.

Apoptosis-Inducing Effects of Short-Chain Fatty Acids-Rich Fermented Pistachio Milk in Human Colon Carcinoma Cells.

Pistachio milk (PM), an extraction product of pistachio, is protein- and fat-dense food. Short-chain fatty acids (SCFAs) are known for inducing cytotoxicity and apoptosis in colon carcinoma cells. This study aimed to find an optimal combination of probiotics that can produce a higher amount of SCFAs in PM. In addition, the anti-cancer effect of fermented PM on human colon carcinoma cells (Caco-2) was determined. The combinations of probiotics were as follows: Streptococcus thermophilus + Lactobacillus bulgaricus (C); C + Lactobacillus acidophilus (C-La); C + Lactobacillus gasseri (C-Lg); C + Bifidobacterium bifidum (C-Bb). The results indicated that fermented PM was produced after a short fermentation time in all the probiotics combinations. C-Bb produced up to 1.5-fold more acetate than the other probiotics combinations did. A significant amount of cytotoxicity, i.e., 78, 56, and 29% cell viability was observed in Caco-2 cells by C-Bb-fermented PM at 1, 2.5 and 5%, respectively. C-Bb-fermented PM (5%) induced early and late apoptosis up to 6-fold. Additionally, Caco-2 cells treated with C-Bb-fermented PM significantly induced the downregulation of α-tubulin and the upregulation of cleaved caspase-3, as well as nuclear condensation and fragmentation. Our data suggest that fermented PM, which is rich in acetate, may have the potential as a functional food possessing anti-colon cancer properties.

Effect of Grafted Insect Protein with Palatinose on Quality Properties of Phosphate-Free Meat Emulsion.

Due to concerns about the negative effects of phosphate on human health, the development of phosphate substitutes is an active area of research. Among the various methods, the structural modification of proteins has previously been established. In this study, we used grafting technology. Extracted insect protein was grafted with palatinose (GI), and 0.1 and 0.15% of GI were added to a phosphate-free meat emulsion mixed with 0.1% of eggshell powder (ES). The pH, myofibrillar protein solubility, and apparent viscosity increased with the addition of GI and ES (p < 0.05). Color values were also affected by GI and ES addition (decreased CIE L* and CIE a* and increased CIE b*; p < 0.05), while cooking loss was only improved by the addition of ES and not GI. Although the total fluid separated more than negative control (p < 0.05), the addition of ES improved emulsion stability and total expressible fluid separation and the fat separation reduced with addition of GI and ES (p < 0.05). Lipid oxidation was inhibited by the addition of GI and ES (p < 0.05). Moreover, the protein molecular weight distribution under 20 kDa was modified by the addition of GI, and the hardness and springiness of treatments decreased. In conclusion, the addition of GI and ES might be used to improve cooking loss, emulsion stability, and antioxidants, while the textural properties should be further researched.

Development of ß-Cyclodextrin/Konjac-Based Emulsion Gel for a Pork Backfat Substitute in Emulsion-Type Sausage.

Emulsion gel has been used to replace animal fats in meat products. Konjac is a widely used gelling agent; however, its low emulsion stability limits its use in meat products. This study aimed to examine the quality characteristics of ß-cyclodextrin (CD)-supplemented konjac-based emulsion gel (KEG) (CD-KEG) and its application as a fat substitute in emulsion-type sausages. The supplementation of CD increased hydrogen bonds and hydrophobic interactions with konjac and oil in the gels, respectively. Additionally, CD increased the structural complexity and strength of KEG. Since adding more than 6% of CD to KEG did not increase the gel strength, 6% CD-added KEG was adopted to substitute for pork backfat in manufacturing low-fat emulsion-type sausages. The following formulations of the sausages were prepared: pork backfat 20% (PF20); pork backfat 10% + KEG 10% (KEG10); KEG 20% (KEG20); pork backfat 10% + CD-KEG 10% (CD-KEG10); CD-KEG 20% (CD-KEG20); and pork backfat 5% (PF5). The CD-KEG20 formulation exhibited higher viscosity and viscoelasticity than KEG20, which suggested that CD improves the rheological properties and the thermal stability of meat batter. Additionally, CD-KEG20 showed similar emulsion stability, cooking yield and texture parameters compared with PF20. Therefore, 6% CD-added KEG is a suitable fat substitute for preparing low-fat emulsion-type sausages.

DIX domain containing 1 (DIXDC1) modulates VEGFR2 level in vasculatures to regulate embryonic and postnatal retina angiogenesis.

BACKGROUND: In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ ß-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ ß-catenin signaling pathways. RESULTS: In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/ß-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis. CONCLUSION: We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.

Effects of Chitosan and Duck Fat-Based Emulsion Coatings on the Quality Characteristics of Chicken Meat during Storage.

Chicken meat is a popular food commodity that is widely consumed worldwide. However, the shelf-life or quality maintenance of chicken meat is a major concern for industries because of spoilage by microbial growth. The aim of this study was to evaluate the effects of chitosan and duck fat-based emulsion coatings on the quality characteristics and microbial stability of chicken meat during refrigerated storage. The coated chicken meat samples were as follows: control (non-coated), DFC0 (coated with duck fat), DFC0.5 (coated with duck fat and 0.5% chitosan), DFC1 (coated with duck fat and 1% chitosan), DFC2 (coated with duck fat and 2% chitosan), and SOC2 (coated with soybean oil and 2% chitosan). The results showed that the apparent viscosity and coating rate were higher in DFC2 than in other groups. Physicochemical parameters (pH, color, and Warner-Bratzler shear force) were better in DFC2 than those in other groups during 15 days of storage. Moreover, DFC2 delayed lipid oxidation, protein deterioration, and growth of microorganisms during storage. These data suggest that chitosan-supplemented duck fat-based emulsion coating could be used to maintain the quality of raw chicken meat during refrigerated storage.

Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells.

Tebuconazole (TEB), a triazole fungicide, is frequently applied to agriculture for the increase of food production. Although TEB causes liver toxicity, its effects on cellular lipid accumulation are rarely investigated. Therefore, this study aimed to study the effects of TEB on lipid metabolism and accumulation in HepG2 cells. HepG2 cells were exposed to 0-320 µM TEB for 1-24 h. TEB (20-80 µM, 24 h)-treated cells showed lipid accumulation. Further, TEB (20-80 µM, 1-12 h) increased the nuclear translocation of peroxisome proliferator-activated receptors and the expression of lipid uptake and oxidation-related markers such as cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5, and carnitine palmitoyltransferase 1. Oxidative stress levels in TEB-treated cells (20-80 µM, 24 h) were higher, compared to those in the control. TEB (20-80 µM, 24 h) also induced the loss of mitochondrial membrane potential and lower levels of microsomal triglyceride transfer protein in the cells. Thus, TEB can induce lipid accumulation by altering the expression of lipid-metabolizing molecules and can therefore impair lipid metabolism. Our data suggest that human exposure to TEB may be a risk factor for non-alcoholic fatty liver disease.

CU06-1004 (endothelial dysfunction blocker) ameliorates astrocyte end-feet swelling by stabilizing endothelial cell junctions in cerebral ischemia/reperfusion injury.

Cerebral ischemia, or stroke, is widespread leading cause of death and disability. Surgical and pharmacological interventions that recover blood flow are the most effective treatment strategies for stroke patients. However, restoring the blood supply is accompanied by severe reperfusion injury, with edema and astrocyte end-feet disruption. Here, we report that the oral administration of CU06-1004 (previously Sac-1004), immediately after onset of ischemia/reperfusion (I/R), ameliorated cerebral damage. CU06-1004 stabilized blood­brain barrier by inhibiting the disruption of the tight junction-related protein zona occludens-1 and the cortical actin ring in endothelial cells (ECs) after I/R. Interestingly, CU06-1004 significantly suppressed astrocyte end-feet swelling following I/R, by reducing aquaporin 4 and connexin 43 levels, which mediates swelling. Furthermore, the degradation of ß1-integrin and ß-dystroglycan, which anchors to the cortical actin ring in ECs, was inhibited by CU06-1004 administration after I/R. Consistently, CU06-1004 administration following I/R also suppressed the loss of laminin and collagen type IV, which bind to the cortical actin ring anchoring proteins. Unlike the protective effects of CU06-1004 in ECs, astrocyte viability and proliferation were not directly affected. Taken together, our observations suggest that CU06-1004 inhibits I/R-induced cerebral edema and astrocyte end-feet swelling by maintaining EC junction stability. KEY MESSAGES: • CU06-1004 ameliorates I/R-induced cerebral injury. • EC junction integrity was stabilized by CU06-1004 treatment after I/R. • CU06-1004 reduces astrocyte end-feet swelling following I/R. • EC junction stability affects astrocyte end-feet structure maintenance after I/R.