The emerging role of redox-sensitive Nrf2-Keap1 pathway in diabetes.

The pathogenic processes involving in the development of diabetes range from autoimmune destruction of pancreatic ß-cells with consequent insulin deficiency to abnormalities that result in resistance to insulin action. The major contributing factor for excessive ß-cell death includes oxidative stress-mediated mitochondrial damage, which creates an imbalance in redox homeostasis. Yet, ß-cells have evolved adaptive mechanisms to endure a wide range of stress conditions to safeguard its potential functions. These include 'Nrf2/Keap1' pathway, a key cellular defense mechanism, to combat oxidative stress by regulating phase II detoxifying and antioxidant genes. During diabetes, redox imbalance provokes defective Nrf2-dependent signaling and compromise antioxidant capacity of the pancreas which turnout ß-cells to become highly vulnerable against various insults. Hence, identification of small molecule activators of Nrf2/Keap1 pathway remains significant to enhance cellular defense to overcome the burden of oxidative stress related disturbances. This review summarizes the molecular mechanism behind Nrf2 activation and the impact of Nrf2 activators in diabetes and its complications.

P21 resists ferroptosis in osteoarthritic chondrocytes by regulating GPX4 protein stability.

Ferroptosis is involved in the pathogenesis of osteoarthritis (OA) while suppression of chondrocyte ferroptosis has a beneficial effect on OA. However, the molecular mechanism of ferroptosis in OA remains to be elucidated. P21, an indicator of aging, has been reported to inhibit ferroptosis, but the relationship between P21 and ferroptosis in OA remains unclear. Here, we aimed to investigate the expression and function of P21 in OA chondrocytes, and the involvement of P21 in the regulation of ferroptosis in chondrocytes. First, we demonstrated that high P21 expression was observed in the cartilage from OA patients and destabilized medial meniscus (DMM) mice, and in osteoarthritic chondrocytes induced by IL-1ß, FAC and erastin. P21 knockdown exacerbated the reduction of Col2a1 and promoted the upregulation of MMP13 in osteoarthritic chondrocytes. Meanwhile, P21 knockdown exacerbated cartilage degradation in DMM-induced OA mouse models and decreased GPX4 expression in vivo. Furthermore, P21 knockdown sensitized chondrocytes to ferroptosis induced by erastin, which was closely associated with the accumulation of lipid peroxides. In mechanism, we demonstrated that P21 regulated the stability of GPX4 protein, and the regulation was independent of NRF2. Meanwhile, we found that P21 significantly affected the recruitment of GPX4 to linear ubiquitin chain assembly complex (LUBAC) and regulated the level of M1-linked ubiquitination of GPX4. Overall, our results suggest that P21 plays an essential anti-ferroptosis role in OA by regulating the stability of GPX4.

Comparative study of rosemary extracts and several synthetic and natural food antioxidants. Relevance of carnosic acid/carnosol ratio.

The antiradical power, at equal concentrations of active principles, of the following antioxidants were studied using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay: butylated-hydroxyanisole, butylated-hydroxytoluene, tert-butylhydroquinone, ascorbyl palmitate, tocopherol, grape seed extract, olive extract and five rosemary extracts with different concentrations of carnosic acid (CA) and carnosol (COL). The reaction kinetics of DPPH scavenging activity in each studied substance identified significant variations in the time needed to reach the steady state. Rosemary extracts were seen to be more effective than the other compounds. CA had higher antioxidant activity than COL, although COL seemed to react faster with DPPH. The relevance of the CA/COL ratio for the antioxidant activity of rosemary extracts was also analysed. The presence of COL in rosemary extracts increased the antioxidant activity with an optimal CA/COL ratio of 2.5-3.0. Olive extract and grape seed extract seem to be very promising additives for use as technological antioxidants.

Interactions of cinnamaldehyde and its metabolite cinnamic acid with human serum albumin and interference of other food additives.

Considering the adverse effect of food additives on humans, thorough research of their physiological effects at the molecular level is important. The interactions of cinnamaldehyde (CNMA), a food perfume, and its major metabolite cinnamic acid (CA) with human serum albumin (HSA) were examined by multiple-spectroscopies. NMR analysis revealed CNMA and CA both bound to HSA, and STD-NMR experiments established CNMA and CA primarily interacted with site I and site II of HSA, respectively. The ligands caused strong quenching of HSA fluorescence through a static quenching mechanism, with hydrophobic and electrostatic interaction between CNMA/CA and HSA, respectively. UV-vis absorption and CD results showed ligands induced secondary structure changes of HSA. Binding configurations were proved by docking method. Furthermore, binding constants of CNMA/CA-HSA systems were influenced by the addition of four other food additives. These studies have increased our knowledge regarding the safety and biological action of CNMA and CA.

Identification and assessment of residual levels of the main oxidation product of tert-butylhydroquinone in frying oils after heating and its cytotoxicity to RAW 264.7 cells.

tert-Butylhydroquinone (TBHQ) losses and the residual levels of 2-tert-butyl-1,4-benzoquinone (TBBQ) in tripalmitin at different heating temperatures with or without reflux over various time intervals were investigated. Heating at 120 °C resulted in the slowest TBHQ loss and the highest TBBQ levels (52.61-62.93 µg/mL). The highest TBBQ concentrations (111.73-164.67 µg/mL) at 5 and 8 h and residual concentrations of 10.23-46.95 µg/mL during heating at 170 °C over 24 h were observed. Furthermore, the potential cytotoxicity of TBBQ to RAW 264.7 cells was evaluated with the MTT assay, Hoechst 33258 staining test, and flow cytometry analysis. Results indicate that TBBQ dose- and time-dependently decreased the growth of cells and inhibited DNA synthesis by regulating the S/G2 transition. The TBBQ concentration giving 50% inhibition in RAW 264.7 cells was 10.71 µg/mL. This threshold value is lower than the residual level of TBBQ in oil, indicating the necessity for concerns over the safety of fried food in terms of TBBQ residues.

NaOH-free debittering of table olives using power ultrasound.

A major drawback to the extension of NaOH-free olive debittering is its lengthy processing. In this research, the power ultrasound efficacy was investigated in a laboratory scale to accelerate this process. Olive fruits were sonicated in water or brine (15% NaCl). The effects of ultrasound-assisted debittering (UAD) were evaluated on olives physicochemical and textural properties in comparison with conventional debittering (CD). In UAD, however, the removal rate of phenolic compounds, which cause olives natural bitterness, increased significantly and as a result, the processing time decreased by 37.8% and 38.6% when debittering was done in water and brine, respectively. The chemical compositions, fatty acids profile, total color differences, Firmness and other textural parameters of UAD-treated samples remained unchanged and their antioxidant activity was significantly higher in comparison with CD-treated samples. Remarkably, UAD was able to speed up and promote NaOH-free olive debittering, without causing any undesirable changes.

Imprinted propyl gallate electrochemical sensor based on graphene/single walled carbon nanotubes/sol-gel film.

A novel imprinted sol-gel electrochemical sensor for the determination of propyl gallate (PG) was developed based on a composite of graphene and single walled carbon nanotubes (GR-SWCNTs). It was fabricated by stepwise modifying GR-SWCNTs and molecularly imprinted polymers and stored in 0.10 mol L(-1) phosphate buffer solution pH 6.0, which endowed the sensor good sensitivity and selective recognition towards template molecules. The morphology and specific adsorption capacity of the sensor was characterized by scanning electron microscope and electrochemical methods, respectively. Under the optimized conditions, a linear range of the sensor to PG was 8.0 × 10(-8)-2.6 × 10(-3)mo lL(-1) with a limit of detection of 5.0 × 10(-8)mol L(-1) (S/N=3). The sensor exhibited specificity and selectivity towards template molecules as well as excellent reproducibility, regeneration and stability. Furthermore, the sensor could be applied to determine PG in edible oils, instant noodles and cookies with satisfactory results.