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Osteosarcoma is the most common primary malignancy of the skeleton in children and adults. The outcomes of people with osteosarcomas are unsatisfied. β-Phenethyl isothiocyanate (PEITC) exhibits chemoprevention and chemotherapeutic activities against many human cancers. The molecular mechanism underlying its action on osteosarcoma is still unknown. This study was aimed at investigating the effect of PEITC on human osteosarcoma both in vitro and in vivo. The results showed that PEITC reduced cell viability, inhibited proliferation, and caused G2/M cell cycle arrest in four human osteosarcoma cell lines (MNNG/HOS, U-2 OS, MG-63, and 143B). Then, we found that PEITC altered iron metabolism related to the processes of iron import, storage, and export, which resulted in increased labile iron. Expectedly, PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation. Multiple cell death modalities, including ferroptosis, apoptosis, and autophagy, were triggered in human osteosarcoma cells. Three MAPKs (ERK, p38, and JNK) were all activated after PEITC treatment; however, they presented different responses among the four human osteosarcoma cell lines. ROS generation was proved to be the major cause of PEITC-induced decreased proliferative potential, altered iron metabolism, cell death, and activated MAPKs in human osteosarcoma cells. In addition, PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose. In conclusion, this study reveals that PEITC simultaneously triggers ferroptosis, apoptosis, and autophagy in human osteosarcoma cells by inducing oxidative stress.

Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC50 value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G2/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers.

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.

Polyacrylate resin composite materials with the mineral exhibit super water absorbency and good degradation ability. In this work, expanded perlite and sodium polyacrylate resin composite materials have been prepared with ceric ammonium nitrate (CAN), N,N’-methylene bisacrylamide (MBA), tapioca starch, and expanded perlite. Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (SEM) are used to characterize the bonds absorption peaks and morphologies. The results suggest that the expanded perlite can graft on sodium polyacrylate resin, and the optimal distilled water and 0.9% NaCl absorbency are 1079 and 253 g/g when the expanded perlite content is 8 wt%, respectively. The swelling water model of the composite materials is firstly simulated to be Voigt-based model. In addition, the composite materials absorbency that is influenced by special characteristics of the expanded perlite has been shown.

Ferroptosis, a form of regulated cell death, is initiated by oxidative perturbations of the intracellular microenvironment, which is under the constitutive control of glutathione peroxidase 4 (GPX4). Ferrous iron (Fe2+) accumulation and lipid peroxidation are critical events in the induction of ferroptosis, which is inhibited by iron chelators and lipophilic antioxidants. Ferroptosis terminates in mitochondrial dysfunction and toxic lipid peroxidation. It plays a vital role in inhibiting cancer growth and proliferation. It can be induced in cancer cells, and certain normal cells, by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3) or clinical drugs. The purpose of this review is to summarize the various drugs (e.g., sulfasalazine, lanperisone, sorafenib, fenugreek (trigonelline), acetaminophen, cisplatin, artesunate, combination of siramesine and lapatinib, ferumoxytol, and salinomycin (ironomycin)) that could induce ferroptosis in cancer cells and provide an overview of current knowledge regarding the mechanisms underlying ferroptosis. In future, we anticipate the development of more ferroptosis-inducing drugs, and the availability of such drugs for the clinical treatment of cancer.

Background Cancer is one of the major threats to human health and current cancer therapies have been unsuccessful in eradicating it. Ferroptosis is characterized by iron-dependence and lipid hydroperoxides accumulation, and its primary mechanism involves the suppression of system Xc−-GSH (glutathione)-GPX4 (glutathione peroxidase 4) axis. Co-incidentally, cancer cells are also metabolically characterized by iron addiction and ROS tolerance, which makes them vulnerable to ferroptosis. This may provide a new tactic for cancer therapy. Scope of review The general features and mechanisms of ferroptosis, and the basis that makes cancer cells vulnerable to ferroptosis are described. Further, we emphatically discussed that disrupting GSH may not be ideal for triggering ferroptosis of cancer cells in vivo, but directly inhibiting GPX4 and its compensatory members could be more effective. Finally, the various approaches to directly inhibit GPX4 without disturbing GSH were described. Major conclusions Targeting system Xc− or GSH may not effectively trigger cancer cells' ferroptosis in vivo the existence of other compensatory pathways. However, directly targeting GPX4 and its compensatory members without disrupting GSH may be more effective to induce ferroptosis in cancer cells in vivo, as GPX4 is essential in preventing ferroptosis. General significance Cancer is a severe threat to human health. Ferroptosis-based cancer therapy strategies are promising, but how to effectively induce ferroptosis in cancer cells in vivo is still a question without clear answers. Thus, the viewpoints raised in this review may provide some references and different perspectives for researchers working on ferroptosis-based cancer therapy.

We aimed to evaluate the biological effects of high static magnetic field (HiSMF, 2–12 Tesla [T]) exposure on mice in a stable and effective breeding environment in the chamber of a superconducting magnet. C57BL/6 mice were bred in the geomagnetic field and HiSMF with different magnetic field strengths (2–4 T, 6–8 T, and 10–12 T) for 28 days. The body weight, blood indices, organ coefficients, and histomorphology of major organs were analyzed. The results showed that the HiSMF had no significant effect on the body weight, organ coefficients, or histomorphology of major organs in mice. The HiSMF had no effect on most routine blood and biochemical indices, but the value of the mean corpuscular hemoglobin (MCH) was increased in the 2–4 T group compared with that of the other groups, and the uric acid level (UA) was decreased in the three HiSMF groups compared with that of the control group. The C57BL/6 mice were not affected when they were exposed to different HiSMF environments for 28 days. • No physiological problems were observed in mice with long-term whole-body exposure to HiSMF.

Four tannins were isolated and identified from Potentilla parvifolia using high-speed counter-current chromatography (HSCCC) in this study. A two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:11:1.2:11, v/v/v/v) was chosen and yielded 18.8 mg of procyanidin B3, 9.8 mg of procyanidin B6, 9.1 mg of procyanidin B7, and 6.9 mg of 2,3,4,6-tetra-O-galloyl-D-glucose, all at over 95% purity, from 120 mg of the crude sample powder. The identifications were performed with 1H NMR and 13C NMR. This is the first report showing the presence of procyanidin B7 and 2,3,4,6-tetra-O-galloyl-D-glucose in the genus Potentilla, and procyanidin B3 and procyanidin B6 were isolated from P. parvifolia for the first time.

A method of using high-speed counter-current chromatography (HSCCC) and semi-preparative reversed-phase liquid chromatography (semi-preparative RPLC) to preparatively separate flavone glucosides and lignan from the crude extracts of Caragana korshinskii has been established for the first time in this study. Five flavone glucosides, including 9 mg of kaempferol 3-O-{β-d-glucopyranosyl(1→2)-[α-l-rhamonopyranosyl(1 → 6)]-β-d-galactopyranoside}, 21 mg of kaempferol 3-O-α-l-rhamnopyranosyl(1→6)-β-d-galactopyranoside-7-O-α-l-rhamnopyranoside, 34 mg of kaempferol 3-O-β-d-galactopyranoside-7-O-α-l-rhamnopyranoside, 27 mg of kaempferol 3-O-β-d-glucopyranosyl-7-O-α-l-rhamnopyranoside, and 14 mg of calycosin 7-O-β-d-glucopyranoside, and one lignan, 16 mg of alangilignoside B, were successfully isolated from 1.8 g of the crude sample through the combination of HSCCC with a two-phase solvent system composed of ethyl acetate–n-butanol–0.5 % formic acid (4:1:5, v/v/v) and semi-preparative RPLC with a mobile phase of methanol–water (20:80, v/v). The purities of the six compounds are all over 95 % as determined by HPLC and the structures are confirmed by the analysis of UV, 1H-NMR, and 13C-NMR and compared with published data.

In this study, we established a flow-rate gradient separation method to isolate four flavan-3-ol compounds with high purity from the seed coat extracts of Iris lactea by high-speed counter-current chromatography (HSCCC). First, the ethyl acetate extract was pre-separated by silica column chromatography fractionation to obtain the enriched flavan-ols sample (EFS). Then, the EFS was separated by HSCCC with a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (0.75:12.5:1:12.5, v/v/v/v) by increasing the flow rate of the mobile phase from 1.5 to 3.0 mL/min after 120 min. The separation temperature was 30°C, the detection wavelength was 280 nm and the revolution speed was 900 rpm. By the optimized HSCCC method, 300 mg of the EFS was separated, yielding 58 mg of procyanidin B3, 72 mg of procyanidin B1, 52 mg of catechin, and 18 mg of procyanidin B7, at a purity of 98.23%, 99.05%, 99.03%, and 96.34% in 240 min. In this work, the flavan-3-ols in I. lactea are partly reviewed and the resul...

Introduction - The dried seeds of Iris lactea have been used in traditional Chinese medicine. Previous studies have been focused on irisquinones while other chemical components are rarely reported. Objective - To establish an efficient high-speed counter-current chromatography (HSCCC) separation method with continuous sample load (CSL) and double-pump balancing (DPB) mode to isolate proanthocyanidins from I. lactea. Methods - Firstly, an ethyl acetate extract of I. lacteawas pre-fractionated by silica column chromatography for the enrichment of proanthocyanidins. Secondly, the enriched proanthocyanidins sample ( EPS) was further fractionated by HSCCC with a two-phase solvent system ethyl acetate: n- butanol: water ( 9: 1: 10, v/ v/ v) using DPB mode. The flow rate of the two phases was 2.2mL/ min, the revolution speed was 900 rpm, the separation temperature was 30 degrees C and the detection wavelength was 280nm. Finally, the structures of the three isolated proanthocyanidins were elucidated by spectroscopic methods and compared with published data. Results - Under the optimized conditions, 600mg of the EPS with six continuous injections ( 100mg/ time) was fractionated, yielding 57mg of prodelphinidin B3, 198mg of procyanidin B3, and 162mg of procyanidin B1, at purities of 97.2%, 98.1% and 97.3%, respectively. Conclusions - The HSCCC separation method with CSL and DPB proved to be rapid, convenient and economical, constituting an efficient strategy for the isolation of proanthocyanidins. Copyright (c) 2015 John Wiley & Sons, Ltd.

A method of using high-speed counter-current chromatography (HSCCC) for preparative isolation and purification of oligostilbenes from the ethanol extracts of seed kernel of Iris lactea Pall. var. chinensis (Fisch.) Koidz was established in this study. Four oligostilbenes were successfully separated and purified by HSCCC with two sets of two-phase solvent system, n-hexane-ethyl acetate-methanol-water (3:6:4.2:5.5, v/v/v/v) in the head-to-tail elution mode for the first separation to mainly isolate vitisin A (58 mg), epsilon-viniferin (76 mg) and peak II (43 mg) from 300 mg of the crude ethanol extracts, and then light petroleum ethyl acetate methanol water (5:5:3:6, v/v/v/v) in the tail-to-head elution mode for the second separation to isolate vitisin B (52 mg) and vitisin C (11 mg) from 100 mg of peak II. The purities of the isolated four oligostilbenes were all over 95.0% as determined by HPLC. Vitisin A, vitisin B and vitisin C, resveratrol tetramers, were isolated from Iris lactea for the first time. The preparation of crude sample was simple and the HSCCC method for the isolation and purification of four oligostilbenes was rapid, efficient and economical. (C) 2015 Elsevier B.V. All rights reserved.

For identification and quantification of flavonoid aglycones in rape bee pollen (RBP) collected from the Qinghai-Tibetan Plateau, a high-performance liquid chromatography (HPLC) separation method with diode array detector (DAD) and atmospheric pressure chemical ionization/mass spectrometric (APCI/MS) detection and four extraction methods (i.e. microwave-assisted extraction, Soxhlet extraction, cold-soaked extraction, and heat reflux extraction) were developed in this study. The identification of flavonoid aglycones was based on retention time and mass spectra by comparison with standards. Results demonstrated that this method showed excellent reproducibility and correlation coefficient, and offered the detection limits of 0.77-15.50 pmol at signal-to-noise ratio of 3. Quercetin and kaempferol were presented in RBP, and microwave-assisted extraction (MAE) was superior to the other three methods in terms of efficiency, convenience and high content of quercetin (1.37 +/- 0.059 mg/g) and kaempferol (23.44 +/- 0.544 mg/g). Our work indicated that: 1) the proposed HPLC-DAD-APCl/MS was an accurate and precise analysis method to identify and quantify the flavonoid aglycones in RBP; and 2) MAE was efficient to extract flavonoids from RBP with short extraction time, low solvent consumption, and homogeneous extraction conditions. (C) 2014 Elsevier Inc. All rights reserved.

Hippophae rhamnoides L., a fruit which is rich in natural chemical ingredients, has become an important raw material of health food, medicine, and cosmetics. In the present work, a method using 2-(5-benzoacridine)ethyl-p-toluenesulfonate as pre-column derivatization reagent with high sensitivity, selectivity, and short separation time was developed to analyze triterpenic acids (TTAs) in H. rhamnoides L. by HPLC with fluorescence detection and simultaneously confirmed by post-column atmospheric pressure chemical ionization-mass spectrometry. The method was validated by linearity, limits of detection (LODs) and lower limits of quantification (LLOQs), precision, and accuracy. Good linear correlations were observed for all TTAs with correlation coefficients greater than 0.9996. LODs and LLOQs were in the range of 1.71-2.14 and 7.45-8.23ngmL(-1), respectively. The method was successfully employed to analyze TTAs in H. rhamnoides L. from various origins in the Qinghai-Tibetan plateau with trace amount of samples within 15min. A systemic mapping of the TTAs in H. rhamnoides L. of different origins was established. The results indicated that H. rhamnoides L. is rich in TTAs, especially in oleanolic and ursolic acids, and the content of TTAs varies across origins. This work will support the research on pharmaceutical applications of H. rhamnoides L. and provide information for quality control.

It is difficult to simultaneously isolate and purify flavonoids and polyhydroxystilbenes due to their similar polarities. In this study, we isolated and purified these compounds from Trigonella foenum-graecum L. seed extracts using high-speed counter-current chromatography (HSCCC) in two steps with two different kinds of solvent systems. In the first step, n-hexane:ethyl acetate:methanol:water (1:5:1:5, v/v) was used as the two-phase solvent system, desoxy-rhaponticin and rhapontigenin were purified, and orientin, vitexin, isovitexin, and rhaponticin were eluted together. In the second step, ethyl acetate:water (1:1, v/v) was used as the two-phase solvent system, and orientin, vitexin, rhaponticin, and isovitexin were isolated and purified. Purities of the isolated compounds were determined using HPLC, while UV spectra, 1 H-NMR, and 13 C-NMR aided in structure identification.

The influence of spring dextrin (SD) on the gelatinized starch retrogradation was investigated by wide X-ray diffraction (WXRD), differential scanning calorimetry (DSC) and molecular dynamic (MD) simulation. Different wheat and corn starch gels were prepared with the addition of SD 3 , SD 5 , SD 7 or SD 9 . WXRD results showed that recrystallinity of wheat and corn starch gels was reduced with the addition of SD 7 or SD 9 . Alternatively, SD 3 or SD 5 accelerated recrystallinity. Enthalpies of retrograde wheat and corn starch gels were analyzed using the Avrami equation and confirmed the WXRD results. Finally, MD simulation was adapted to predict the interaction of SD and starch fraction in water, and the results showed that the SD disturbed starch retrogradation by altering starch fraction–starch fraction interaction. Based on the obtained results of WXRD, DSC and MD, it was concluded that the addition of SDs significantly influences starch long-term retrogradation.

Naturally occurring oligostilbenes are receiving more attention because they exhibit several beneficial effects for health, including hepatoprotective, antitumor, anti-adipogenic, antioxidant, antiaging, anti-inflammatory, anti-microbial, antiviral, immunosuppressive and neuroprotective activities. Thus, they could be of some potentially therapeutic values for several diseases. In this study, we adopted the alkaline extraction-acid precipitation (AEAP) method for extraction of oligostilbenes from the seed kernel of Iris lactea Then, the high-speed counter-current chromatography (HSCCC) was used for preparative isolation and purification of oligostilbenes from the AEAP extracts. Finally, three oligostilbenes, namely vitisin D (73 mg), ampelopsin B (25 mg) and cis-vitisin A (16 mg), were successfully fractionated by HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (2:5:3:6, v/v/v/v) from 300 mg of the AEAP extracts in ∼ 190 min. The purities of the three isolated oligostilbenes were all over 95.0% as analyzed by high performance liquid chromatography. They all were isolated from I. lacteal for the first time.The method of AEAP for the preparation of the oligostilbene-enriched crude sample was simple, and the HSCCC technique for the isolation and purification of oligostilbenes was efficient.