A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells.

The increasing drug efflux through the ATP-binding cassette (ABC) transporters is the most plausible mechanism that mediates resistance to the anticancer phytochemicals, such as benzyl isothiocyanate (BITC), as well as chemotherapy drugs. To identify a potential component to overcome this resistance by combinatory utilization, we focused on multidrug resistance-associated proteins (MRPs) pumping various drug metabolites with glutathione as well as the organic anions. The pharmacological treatment of an MRP inhibitor, MK571, significantly potentiated the BITC-induced antiproliferation, coincided with the enhanced accumulation of BITC and glutathione in human colorectal cancer HCT-116 cells. MK571 also enhanced the apoptosis induction as well as activation of the mitogen-activated protein kinases and caspase-3, whereas it did not affect their basal levels. These results suggested that, since MRPs might play a pivotal role in the BITC efflux, MK571 potentiates the BITC-induced antiproliferation in human colorectal cancer cells through inhibition of the glutathione-dependent BITC efflux.

Methyl-ß-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells.

Methyl-ß-cyclodextrin (MßCD) is an effective agent for the removal of plasma membrane cholesterol. In this study, we investigated the modulating effects of MßCD on the antiproliferation induced by benzyl isothiocyanate (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that MßCD dose-dependently increased the cholesterol level in the medium, possibly through its removal from the plasma membrane of human colorectal cancer cells. The pretreatment with a non-toxic concentration (2.5 mM) of MßCD significantly enhanced the BITC-induced cytotoxicity and apoptosis induction, which was counteracted by the cholesterol supplementation. Although BITC activated the phosphoinositide 3-kinase (PI3K)/Akt pathway, MßCD dose-dependently inhibited the phosphorylation level of Akt. On the contrary, the treatment of MßCD enhanced the phosphorylation of mitogen activated protein kinases, but did not potentiate their BITC-induced phosphorylation. These results suggested that MßCD might potentiate the BITC-induced anti-cancer by cholesterol depletion and thus inhibition of the PI3K/Akt-dependent survival pathway. Abbreviations: CDs: cyclodextrins; MßCD: methyl-ß-cyclodextrin; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; PI3K: phosphoinositide 3-kinase; PDK1: phosphoinositide-dependent kinase-1; MAPK: mitogen activated protein kinase; ERK1/2: extracellular signal-regulated kinase1/2; JNK: c-Jun N-terminal kinase; PI: propidium iodide; FBS: fatal bovine serum; TLC: thin-layer chromatography; PBS(-): phosphate-buffered saline without calcium and magnesium; MEK: MAPK/ERK kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PIP3: phosphatidylinositol-3,4,5-trisphosphate.

Elucidating the effects of precooked treatments on the quality attributes of red swamp crayfish (Procambarus clarkia): Insights from water boiling vs. microwaving.

Precooked treatments are essential in food processing, extending beyond mere sterilization to include the enhancement of nutritional value, flavor profile, and digestibility. This research scrutinizes the effects of water boiling and microwaving on red swamp crayfish, two distinct precooked methodologies. A comparative analytical framework has been employed to assess the efficacy of two precooked methods across a spectrum of quality indicators, including aerobic plate counts, texture, nutrient composition, volatile compound characterization, protein oxidation, and digestive properties. The findings revealed that both water boiling and microwaving effectively reduced bacterial counts to a safe level of 500 CFU/g. Microwave precooking facilitated a moderate oxidation of lipids in crayfish, preferentially liberating flavor compounds, thereby enhancing their sensory attributes. The boiling process imparted a pronounced denaturation to proteins, consequently augmenting the hardness of the crayfish. Notably, the enhanced digestibility of boiled crayfish proteins results from the denaturing action of boiling, promoting efficient protein digestion.

Water extract from artichoke ameliorates high-fat diet-induced non-alcoholic fatty liver disease in rats.

BACKGROUND: The "multiple-hit" hypothesis is currently the most widely accepted theory for non-alcoholic fatty liver disease (NAFLD) pathogenesis. The present study aimed to investigate the effects of the water extract of artichoke (WEA) on NAFLD and its underlying mechanism. METHODS: Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD and then treated with WEA at three doses (0.4, 0.8, and 1.6 g/kg body weight, BW) for 8 weeks. At the end of the intervention, serum biochemical parameters, hepatic antioxidant capacity, hepatic levels of pro-inflammatory cytokines, liver histopathology, hepatic inflammatory gene and lipid metabolism gene expression, and Akt and p-Akt (S473) protein levels were determined. RESULTS: The body weight, liver weight, liver triglyceride (TG) and serum levels of TG, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, glucose, and insulin were all significantly reduced in the WEA-treated groups (0.8 and 1.6 g/kg BW) compared with the HFD group (P < 0.01). A significant decrease in hepatic content of malondialdehyde (P < 0.01) and glutathione (P < 0.01), as well as a significant increase in liver superoxide dismutase activity (P < 0.01) were observed in WEA-treated groups (0.8 and 1.6 g/kg BW) compared to the HFD group. In addition, there was a marked decrease in the hepatic levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the WEA-treated groups compared to the HFD group (P < 0.01). In line with these findings, the histopathology of the livers of rats treated with WEA (0.8 and 1.6 g/kg BW) showed a decrease in steatosis, ballooning, and lobular inflammation. Mechanistically, the reduced hepatic TG content might be related to the downregulation of lipogenic genes (SREBP1c, FASN, SCD1) and upregulation of lipolytic gene (PPARα), and the improved insulin signaling might be associated with the observed increase in antioxidant activity and reduction in inflammation in the WEA-treated groups. CONCLUSION: The hepatoprotective role of WEA in NAFLD may be attributed to its anti-steatotic, antioxidant, anti-inflammatory, and anti-insulin resistance effects.

An integrated and conductive hydrogel-paper patch for simultaneous sensing of Chemical-Electrophysiological signals.

Simultaneous monitoring of electrophysiological and biochemical signals is of great importance in healthcare and fitness management, while the fabrication of highly integrated and flexible devices is crucial to these applications. Herein, we devised a multifunctional and flexible hydrogel-paper patch (HPP) that was capable of simultaneously real-time monitoring of electrocardiogram (ECG) signal and biochemical signal (glucose content) in sweat during exercise. The self-assembly of the highly porous PEDOT:PSS hydrogel on paper fiber provided the HPP with good conductivity and hydrophilic wettability for efficient electron transmission and substance diffusion, thereby enabling it to serve as a low-impedance ECG electrode and a highly sensitive glucose sensor. Additionally, the spontaneous capillary flow effect allows the paper patch to be used as microfluidic channels for the collect and analysis of sweat. Moreover, the HPP is integrated with a flexible printed circuit board (FPCB) and works as a multifunctional wearable device mounted on the chest for real-time monitoring of electrophysiological and biochemical signals during exercise.