Dietary supplementation with quercetin: an ideal approach for improving meat quality and oxidative stability of broiler chickens.

This study aimed to improve the eating quality of yellow-feathered broiler chicks by feeding them corn-soybean meal diets supplemented with 250, 500, and 1,000 mg/kg quercetin. we examined the impact of varying doses of dietary quercetin on the sensory quality of chicken breast meat as well as on the antioxidant enzymes, antioxidant-related signaling molecules, structure and thermal stability of myofibrillar protein (MPs), and microstructure of myogenic fibers in the meat during 24 h of postslaughter aging. Additionally, we investigated the potential correlations among antioxidant capacity, MP structure, and meat quality parameters. The results indicated that dietary supplementations with 500 and 1,000 mg/kg quercetin improved the physicochemical properties and eating quality of yellow-feathered broiler chicken breast meat during 12 to 24 h postslaughter. Additionally, quercetin improved the postslaughter oxidative stress status and reduced protein and lipid oxidation levels. It also increased hydrogen bonding interactions and α-helix content during 6 to 12 h postslaughter and decreased ß-sheet content during 12 to 24 h postslaughter in chicken breast MP. This resulted in improved postslaughter MP structure and thermal stability. The correlation results indicated that the enhancement of antioxidant capacity and MP structure enhanced the physicochemical and edible qualities of yellow-feathered broiler chicken breast meat. In conclusion, the current findings suggest that dietary supplementation with quercetin is an ideal approach for improving the eating quality of chicken meat, thereby broadening our understanding of theoretical and technological applications for improving the quality of chicken.

Probiotic Characteristics and Anti-Inflammatory Effects of Limosilactobacillus fermentum 664 Isolated from Chinese Fermented Pickles.

Limosilactobacillus fermentum (L. fermentum) is widely used in industrial food fermentations, and its probiotic and health-promoting roles attracted much attention in the past decades. In this work, the probiotic potential of L. fermentum 664 isolated from Chinese fermented pickles was assessed. In addition, the anti-inflammatory properties and mechanisms were investigated using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results indicated that L. fermentum 664 demonstrated excellent acid and bile salt tolerance, adhesion capability, antimicrobial activity, and safety profile. L. fermentum 664 downregulated the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and cyclooxygenase-2 (COX-2) stimulated with LPS. Moreover, L fermentum 664 inhibited the nuclear translocation of the nuclear factor κB (NF-κB) and the activation of mitogen-activated protein kinases (MAPKs) induced by LPS. This action was associated with a reduction in reactive oxygen species (ROS) levels and an enhanced expression of heme oxygenase-1 (HO-1) protein. Additionally, whole genome sequencing indicated that L. fermentum 664 contained genes that encode proteins with antioxidant and anti-inflammatory functions, including Cytochrome bd ubiquinol oxidase subunit I (CydA), Cytochrome bd ubiquinol oxidase subunit II (CydB), and NAD(P)H dehydrogenase quinone 1 (NQO1). In conclusion, our study suggested that L. fermentum 664 has the potential to become a probiotic and might be a promising strategy for the prevention of inflammation.

Vitamin B12-Induced Autophagy Alleviates High Glucose-Mediated Apoptosis of Islet ß Cells.

High glucose levels can lead to the apoptosis of islet ß cells, while autophagy can provide cytoprotection and promote autophagic cell death. Vitamin B12, a water-soluble B vitamin, has been shown to regulate insulin secretion and increase insulin sensitivity. However, the precise mechanism of action remains unclear. In this study, we investigated the influence of vitamin B12 on high glucose-induced apoptosis and autophagy in RIN-m5F cells to elucidate how vitamin B12 modulates insulin release. Our results demonstrate that exposure to 45 mM glucose led to a significant increase in the apoptosis rate of RIN-m5F cells. The treatment with vitamin B12 reduced the apoptosis rate and increased the number of autophagosomes. Moreover, vitamin B12 increased the ratio of microtubule-associated protein 1 light chain 3 beta to microtubule-associated protein 1 light chain 3 alpha (LC3-II/LC3-I), while decreasing the amount of sequestosome 1 (p62) and inhibiting the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K) under both normal- and high-glucose conditions. The additional experiments revealed that vitamin B12 inhibited high glucose-induced apoptosis. Notably, this protective effect was attenuated when the autophagy inhibitor 3-methyladenine was introduced. Our findings suggest that vitamin B12 protects islet ß cells against apoptosis induced by high glucose levels, possibly by inducing autophagy.

Expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma.

Objective: To investigate the expression and correlation of COX-2 and NUCB1 in colorectal adenocarcinoma and adjacent tissues. Methods: The expression of COX-2 and NUCB1 and their effects on prognosis were predicted using bioinformatics. Immunohistochemistry was used to identify the expression of two molecules in 56 cases of colorectal adenocarcinoma and the surrounding tissues. The expression of two molecules and their association with clinicopathological variables were examined using the chi-square test. The association between COX-2 and NUCB1 was investigated using the Spearman correlation test. Results: The STRING database revealed that COX-2 and NUCB1 were strongly linked. According to the UALCAN and HPA database, COX-2 was upregulated while NUCB1 was downregulated in colorectal adenocarcinoma, both at the protein and gene levels. The OS times for COX-2 and NUCB1 high expression, however, exhibited the same patterns. The rate of positive COX-2 immunohistochemical staining in cancer tissues was 69.64% (39/56), which was significantly higher than the rate in healthy tissues 28.57% (16/56). NUCB1 was expressed positively in cancer tissues at a rate of 64.29% (36/56) compared to just 19.64% (11/56) in neighboring tissues. The positive expression levels of COX-2 and NUCB1 were both closely related to clinical stage, differentiation degree, and lymphatic metastases (P < 0.05). In colorectal cancer, COX-2 and NUCB1 expression were significantly correlated (rs = 0.6312, P < 0.001). Conclusion: Both COX-2 and NUCB1 are overexpressed and significantly associated in colorectal adenocarcinoma.

Separation of m-cresol and p-cresol by NaZSM-5 with different Si/Al ratios.

m-Cresol and p-cresol are widely used in medicine and pesticides as important chemical intermediates. They are generally produced as a mixture in industry and are difficult to separate due to the similarities in both chemical structures and physical properties. The adsorption behaviours of m-cresol and p-cresol on zeolites (NaZSM-5 and HZSM-5) with different Si/Al ratios have been compared by static experiments. Selectivity on NaZSM-5(Si/Al = 80) could be greater than 6.0. Adsorption kinetics and isotherms were investigated in detail. The kinetic data was correlated by PFO, PSO, and ID models, the NRMSE of which were 14.03%, 9.41%, and 21.11%, respectively. In the meanwhile, according to the NRMSE of Langmuir (6.01%), Freundlich (57.80%), D-R (1.1%), and Temkin (0.56%) isotherms, adsorption on NaZSM-5(Si/Al = 80) was mainly a monolayer and chemical adsorption process. It was endothermic for m-cresol and exothermic for p-cresol. The Gibbs free energy, entropy, and enthalpy were calculated accordingly. The adsorption of cresol isomers on NaZSM-5(Si/Al = 80) were both spontaneous, and it was exothermic (ΔH = -37.11kJ/mol) for p-cresol while endothermic (ΔH = 52.30kJ/mol) for m-cresol. Additionally, ΔS were respectively -0.05 and 0.20 kJ·mol-1·K-1for p-cresol and m-cresol, which were both close to zero. The adsorption was mainly driven by enthalpy. The result of breakthrough further demonstrated m-cresol and p-cresol could be separated effectively by NaZSM-5(Si/Al = 80). Additionally, the selectivity increased from 7.53 to 14.72 after four cycles regeneration with 9.95% and 53.96% decreases in the adsorption amounts for m-cresol and p-cresol, respectively. In conclusion, NaZSM-5(Si/Al = 80) could be a feasible adsorbent for the separation of m-cresol and p-cresol.

Carbon Quantum Dots from Roasted Coffee Beans: Their Degree and Mechanism of Cytotoxicity and Their Rapid Removal Using a Pulsed Electric Field.

Carbon quantum dots (CQDs) from heat-treated foods show toxicity, but the mechanisms of toxicity and removal of CQDs have not been elucidated. In this study, CQDs were purified from roasted coffee beans through a process of concentration, dialysis and lyophilization. The physical properties of CQDs, the degree and mechanism of toxicity and the removal method were studied. Our results showed that the size of CQDs roasted for 5 min, 10 min and 20 min were about 5.69 ± 1.10 nm, 2.44 ± 1.08 nm and 1.58 ± 0.48 nm, respectively. The rate of apoptosis increased with increasing roasting time and concentration of CQDs. The longer the roasting time of coffee beans, the greater the toxicity of CQDs. However, the caspase inhibitor Z-VAD-FMK was not able to inhibit CQDs-induced apoptosis. Moreover, CQDs affected the pH value of lysosomes, causing the accumulation of RIPK1 and RIPK3 in lysosomes. Treatment of coffee beans with a pulsed electric field (PEF) significantly reduced the yield of CQDs. This indicates that CQDs induced lysosomal-dependent cell death and increased the rate of cell death through necroptosis. PEF is an effective way to remove CQDs from roasted coffee beans.

A Novel Method in Identifying Pyroptosis and Apoptosis Based on the Double Resonator Piezoelectric Cytometry Technology.

In this study, a double resonator piezoelectric cytometry (DRPC) technology based on quartz crystal microbalance (QCM) was first employed to identify HeLa cell pyroptosis and apoptosis by monitoring cells' mechanical properties in a real-time and non-invasive manner. AT and BT cut quartz crystals with the same frequency and surface conditions were used concurrently to quantify the cells-exerted surface stress (ΔS). It is the first time that cells-exerted surface stress (ΔS) and cell viscoelasticity have been monitored simultaneously during pyroptosis and apoptosis. The results showed that HeLa pyroptotic cells exerted a tensile stress on quartz crystal along with an increase in the elastic modulus (G'), viscous modulus (G″), and a decrease of the loss tangent (G″/G'), whereas apoptotic cells exerted increasing compressive stress on quartz crystal along with a decrease in G', G″ and an increase in G″/G'. Furthermore, engineered GSDMD-/--DEVD- HeLa cells were used to investigate drug-induced disturbance and testify the mechanical responses during the processes of pyroptosis and non-pyroptosis. These findings demonstrated that the DRPC technology can serve as a precise cytomechanical sensor capable of identifying pyroptosis and apoptosis, providing a novel method in cell death detection and paving the road for pyroptosis and apoptosis related drug evaluation and screening.

Vitamin B6 Inhibits High Glucose-Induced Islet ß Cell Apoptosis by Upregulating Autophagy.

Vitamin B6 may alleviate diabetes by regulating insulin secretion and increasing insulin sensitivity, but its mechanism remains to be explored. In this study, vitamin B6-mediated autophagy and high glucose-induced apoptosis were tested to investigate the mechanism by which vitamin B6 regulates insulin release. The results showed that 20 mM glucose increased the apoptosis rate from 10.39% to 22.44%. Vitamin B6 reduced the apoptosis rate of RIN-m5F cells from 22.44% to 11.31%. Our data also showed that the vitamin B6 content in processed eggs was decreased and that the hydrothermal process did not affect the bioactivity of vitamin B6. Vitamin B6 increased the number of autophagosomes and the ratio of autophagosome marker protein microtubule associated protein 1 light chain 3 beta to microtubule associated protein 1 light chain 3 alpha (LC3-II/LC3-I). It also decreased the amount of sequetosome 1 (SQSTM1/p62) and inhibited the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K) under normal and high glucose stress. Another study showed that vitamin B6 inhibited the apoptosis rate, whereas the autophagy inhibitor 3-methyladenine (3-MA) blocked the protective effect of vitamin B6 against apoptosis induced by high glucose. The hydrothermal process decreased the vitamin B6 content in eggs but had no effect on the cytoprotective function of vitamin B6 in RIN-m5f cells. In conclusion, we demonstrated that vitamin B6-mediated autophagy protected RIN-m5f cells from high glucose-induced apoptosis might via the mTOR-dependent pathway. Our data also suggest that low temperatures and short-term hydrothermal processes are beneficial for dietary eggs.

Tumor microenvironment-associated lactate metabolism regulates the prognosis and precise checkpoint immunotherapy outcomes of patients with lung adenocarcinoma.

BACKGROUND: Despite the wide clinical application of checkpoint inhibitor immunotherapy in lung adenocarcinoma, its limited benefit to patients remains puzzling to researchers. One of the mechanisms of immunotherapy resistance may be the dysregulation of lactate metabolism in the immunosuppressive tumor microenvironment (TME), which can inhibit dendritic cell maturation and prevent T-cell invasion into tumors. However, the key genes related to lactate metabolism and their influence on the immunotherapeutic effects in lung adenocarcinoma have not yet been investigated in depth. METHODS: In this study, we first surveyed the dysregulated expression of genes related to lactate metabolism in lung adenocarcinoma and then characterized their biological functions. Using machine learning methods, we constructed a lactate-associated gene signature in The Cancer Genome Atlas cohort and validated its effectiveness in predicting the prognosis and immunotherapy outcomes of patients in the Gene Expression Omnibus cohorts. RESULTS: A 7-gene signature based on the metabolomics related to lactate metabolism was found to be associated with multiple important clinical features of cancer and was an independent prognostic factor. CONCLUSIONS: These results suggest that rather than being simply a metabolic byproduct of glycolysis, lactate in the TME can affect immunotherapy outcomes. Therefore, the mechanism underlying this effect of lactate is worthy of further study.

Lactate: The Mediator of Metabolism and Immunosuppression.

The Warburg effect, one of the hallmarks of tumors, produces large amounts of lactate and generates an acidic tumor microenvironment via using glucose for glycolysis. As a metabolite, lactate not only serves as a substrate to provide energy for supporting cell growth and development but also acts as an important signal molecule to affect the biochemical functions of intracellular proteins and regulate the biological functions of different kinds of cells. Notably, histone lysine lactylation (Kla) is identified as a novel post-modification and carcinogenic signal, which provides the promising and potential therapeutic targets for tumors. Therefore, the metabolism and functional mechanism of lactate are becoming one of the hot fields in tumor research. Here, we review the production of lactate and its regulation on immunosuppressive cells, as well as the important role of Kla in hepatocellular carcinoma. Lactate and Kla supplement the knowledge gap in oncology and pave the way for exploring the mechanism of oncogenesis and therapeutic targets. Research is still needed in this field.

Heliothis virescens ascovirus 3h blocks the cell cycle of Spodoptera exigua fat body cells at G2 /M phase by downregulating cyclin B1 and cyclin-dependent kinase 1.

Ascoviruses are double-stranded DNA viruses that are pathogenic to noctuid larvae. In vitro infection causes the cells to fail to replicate and proliferate normally. However, the molecular mechanisms are unclear. In this study, the transmission electron microscopy data of infected-Spodoptera exigua (Hübner) fat body cells (SeFB, IOZCAS-SpexII-A cells) showed that virions were internalized in phagocytic vesicles, but not in the nucleus. FACS of cell-cycle progression was performed in SeFB cells infected with Heliothis virescens ascovirus 3h (HvAV-3h). The cell cycle phase distributions of the SeFB cells were G1 = 29.52 ± 1.10%, S = 30.33 ± 1.19%, and G2 /M = 40.06 ± 0.75%. The cell culture doubling time was approximately 24 h. The G1 , S, and G2 /M phases were each approximately 8 h. The unsynchronized or synchronized cells were arrested at G2 /M phase after infection with HvAV-3h. Our data also showed that cells with more than 4N DNA content appeared in the HvAV-3h-treated group. While the mRNA levels of cyclin B1 , cyclin H, and cyclin-dependent kinase 1 (CDK1) were downregulated after HvAV-3h infection, the mRNA expression levels of cyclin A, cyclin D, and cyclin B2 were not significantly changed. Western blotting results showed that the expression of cyclin B1 and CDK1 in infected SeFB cells within 24 h postinfection (hpi), and HvAV-3h infection inhibited the expression of cyclin B1 and CDK1 at 12-24 hpi. Overall, these data implied that HvAV-3h infection leads to an accumulation of cells in the G2 /M phases by downregulating the expression of cyclin B1 and CDK1.

Tripartite motif-containing protein 11 promotes hepatocellular carcinogenesis through ubiquitin-proteasome-mediated degradation of pleckstrin homology domain leucine-rich repeats protein phosphatase 1.

BACKGROUND AND AIMS: HCC is one of the main types of primary liver cancer, with high morbidity and mortality and poor treatment effect. Tripartite motif-containing protein 11 (TRIM11) has been shown to promote tumor formation in lung cancer, breast cancer, gastric cancer, and so on. However, the specific function and mechanism of TRIM11 in HCC remain open for study. APPROACH AND RESULTS: Through clinical analysis, we found that the expression of TRIM11 was up-regulated in HCC tissues and was associated with high tumor node metastasis (TNM) stages, advanced histological grade, and poor patient survival. Then, by gain- and loss-of-function investigations, we demonstrated that TRIM11 promoted cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Mechanistically, RNA sequencing and mass spectrometry analysis showed that TRIM11 interacted with pleckstrin homology domain leucine-rich repeats protein phosphatase 1 (PHLPP1) and promoted K48-linked ubiquitination degradation of PHLPP1 and thus promoted activation of the protein kinase B (AKT) signaling pathway. Moreover, overexpression of PHLPP1 blocked the promotional effect of TRIM11 on HCC function. CONCLUSIONS: Our study confirmed that TRIM11 plays an oncogenic role in HCC through the PHLPP1/AKT signaling pathway, suggesting that targeting TRIM11 may be a promising target for the treatment of HCC.

Systematic thermodynamic analysis of apremilast polymorphs via solubility measurement with modeling: Mechanism evaluation through molecular simulation.

The polymorphism of apremilast has been investigated. Two polymorphs have been identified and characterized by differential scanning calorimeter, fourier transform infrared spectroscopy, and powder X-ray diffractometer. Solubilities of apremilast forms B and E in three binary solvents of methanol-water, acetonitrile-water, and acetonitrile-methanol have been measured using the static method at a temperature ranging from 288.15 K to 328.15 K under standard atmospheric pressure. Subsequently, the solubility data have been analyzed using the Wilson, NRTL, and UNIQUAC thermodynamic models, respectively. Furthermore, the Gibbs energy of solution and the radial distribution function have been calculated using the molecular simulation method to evaluate the dissolution mechanism. The Gibbs energy of solution reveals that the rank of solute-solvent interaction correlated well with solubility order in binary solvent mixtures, and the radial distribution function indicates that weakening of solvent-solvent interaction led to an increase in solubility.

Study on Dissolution Thermodynamics and Cooling Crystallization of Rifamycin S.

The solubility data of rifamycin S were measured in isopropanol, butyl acetate, and their mixed solvents across the temperature range of 283.15-323.15 K by the gravimetric method. The results demonstrate that the solubility of rifamycin S increases with the increasing temperature in the two pure solvents, and in the mixed solvents, it increases first and then decreases with increasing butyl acetate content. The experimental data of rifamycin S in the mixed solvents were better correlated using the modified Apelblat equation and ideal model equation. Furthermore, the relevant thermodynamic parameters of the dissolution process were determined based on the van't Hoff equation. The obtained dissolution enthalpy and Gibbs free energy are positive in all cases, which indicate that the dissolving process of rifamycin S is endothermic and nonspontaneous. The supersolubility data of rifamycin S were measured by the laser and thermal analytic method. The results demonstrate that the width of the metastable zone of rifamycin S becomes larger with decreasing cooling rate and increasing butyl acetate content. Furthermore, the crystallization process of rifamycin S was optimized on the basis of thermodynamic research. The results showed that when V butyl acetate:V mixed solvent was 0.04, the cooling rate was 0.1 K/min, the stirring rate was 150 rpm, the final crystallization temperature was 283.15 K, and the aging time was 8 h, the purity of rifamycin S crystals could reach 98.5%, and the crystalline yield was 89.6%. After crystallization optimization, the size of rifamycin S crystals increased, and the dissolution in water was improved.

Fluorescence nanoparticles from instant coffee accumulated in lysosome and induced lysosome-dependent cell death via necroptosis-like pathway.

Fluorescence nanoparticles (FNs) are a type of nano-dots generated during baking process, and their safety on organism is unclear and little is known to their cytotoxicity. In this study, the FNs from instant coffee were purified and characterized. The FNs with an average size about 2.08 nm emitted bright blue fluorescence with lifetime about 2.74 ns. The element and functional groups were analyzed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, respectively. The results indicated that these FNs were internalized in lysosomes and induced apoptosis of normal rat kidney (NRK) and Caco-2 cells. While, the pan-caspase inhibitor, Z-VAD-FMK didn't decrease the rate of apoptosis and cell death of the FNs-treated NRK and Caco-2 cells. These internalized FNs enlarged lysosomes, decreased lysosomal enzyme degradation activity and increased lysosomal pH value. Partial co-localization of receptor-interacting serine-threonine kinase 3 (RIPK3) to lysosomes in FNs-treated cells was observed, and the amount of RIPK1 and RIPK3 increased after treatment with FNs. The results demonstrated that the FNs from instant coffee induced lysosomal membrane permeabilization and initiated necroptosis.

Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.

BACKGROUND: This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. METHODS: This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. RESULTS: A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. CONCLUSIONS: Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.

Carbon dots from roasted chicken accumulate in lysosomes and induce lysosome-dependent cell death.

Thermal processing may generate toxicants. Carbon dots (CDs) from baked foods are toxic to cells; however, their molecular mechanism is still unexplored to date. The present study investigated the effects of CDs from roasted chicken breasts on normal rat kidney (NRK) and Caco-2 cells. The average size of CDs heated at 200 °C and 300 °C was about 2.8 nm and 1.2 nm, respectively. The element and surface groups of CDs were analyzed via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR), respectively. It was confirmed that the CDs were internalized in lysosomes and induced apoptosis. Furthermore, Z-VAD-FMK did not decrease the rate of apoptosis. The acquired data further confirmed that these internalized CDs enlarged lysosomes, decreased the lysosomal enzyme degradation activity and increased the lysosomal pH value. An increase in the co-localization of RIPK3 in lysosomes in the CD-treated groups was observed. The CD treatment increased the protein level of receptor interaction protein 1 (RIPK1) and receptor interaction protein 3 (RIPK3). Overall, CDs from the baked chicken breast induced lysosomal membrane permeabilization and initiated lysosome-dependent cell death and necroptosis. Our results elucidated the toxic mechanism of CDs from baked chicken breast and implied that food thermal processing at a lower temperature is beneficial to human health.

Delphinidin-induced autophagy protects pancreatic ß cells against apoptosis resulting from high-glucose stress via AMPK signaling pathway.

Hyperglycemia, a diagnostic characteristic of diabetes mellitus, is detrimental to pancreatic ß cells. Delphinidin, a member of the anthocyanin family, inhibits glucose absorption, increases glucagon-like peptide-1 (GLP-1) secretion, and improves insulin secretion in diabetes. However, whether delphinidin plays a protective role in pancreatic ß-cell mass and function is not clear. In this study, delphinidin was found to decrease the high-glucose-induced apoptosis of RIN-m5F pancreatic ß cells. In addition, delphinidin induced autophagy in RIN-m5F cells under the normal and high-glucose conditions, while 3-methyladenine (3-MA) inhibition of autophagy significantly diminished the protective role of delphinidin against high-glucose-induced apoptosis of pancreatic ß cells. Delphinidin also decreased the level of cleaved caspase 3 and increased the phosphorylation level of AMP-activated protein kinase α (AMPKα) Thr172. Compound C, an AMPK inhibitor, was found to decrease the ratio of LC3-II/LC3-I, and the apoptotic rate of high-glucose-injured cells was increased after treatment with delphinidin, indicating that delphinidin attenuated the negative effects of high-glucose stress to cells. In conclusion, our data demonstrate that delphinidin protects pancreatic ß cells against high-glucose-induced injury by autophagy regulation via the AMPK signaling pathway. These findings might shed light on the underlying mechanisms of diabetes and help improve the prevention and therapy of this common disease.

Food-borne nanocarriers from roast beef patties for iron delivery.

Food-borne nanoparticles (FNs) produced during thermal processing of food may have potential as nanocarriers for Fe(ii) supplements. In this paper, the FNs in beef patties roasted for different times (15, 30, and 45 minutes) and the binding between FNs and ferrous ions were studied. The size of FNs decreased from 7.5 to 3.0 nm with the increase of baking time, and the FNs emitted bright blue fluorescence under ultraviolet light irradiation. The combination of FNs with ferrous ions was by means of the amino, hydroxyl and carboxyl functional groups on the particles. Cell viability study showed that the Fe(ii)-FNs increased the apoptotic rate, but significantly decreased the necrosis rate, which led to an increase in the number of living cells. In addition, the Fe(ii)-FNs can easily enter the Caco-2 cytoplasm, but not the cellular nucleus. The FNs derived from beef patties with an ultra-small size, high water solubility and plenty of functional groups might be good candidates as nanocarriers for Fe(ii) delivery.

Glibenclamide-Induced Autophagy Inhibits Its Insulin Secretion-Improving Function in ß Cells.

Diabetes is a metabolic disease, partly due to hypoinsulinism, which affects ∼8% of the world's adult population. Glibenclamide is known to promote insulin secretion by targeting ß cells. Autophagy as a self-protective mechanism of cells has been widely studied and has particular physiological effects in different tissues or cells. However, the interaction between autophagy and glibenclamide is unclear. In this study, we investigated the role of autophagy in glibenclamide-induced insulin secretion in pancreatic ß cells. Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. Inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA) potentiated the secretory function of glibenclamide further. These results suggest that glibenclamide-induced autophagy plays an inhibitory role in promoting insulin secretion by activating the AMPK pathway instead of altering the mammalian target of rapamycin (mTOR).