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For decades, pine nut oil Pickering emulsions have been stabilized using a covalent composite of two phenolic chemicals (tannic acid, TA; and gallic acid, GA) and whey protein isolate (WPI) following alkali treatment. Based on covalent composite particles being excellent sources of high-quality stabilizers, this research explored the influence of phenolic addition and hydroxyl content on stability, rheological parameters and characterization of Pickering emulsions.Tannic acid was more effective in reducing the average particle size of the emulsion, which decreased from 479.4 ± 2.1 nm without addition to between 187.6 ± 5.9 and 368.2 ± 16.8 nm (P 0.05). The potential values of all the emulsions were between -30 and -50 mV (except for the gallic acid addition of 2.5 g kgBoth phenolic compounds significantly improved the physicochemical stability of the emulsions (P 0.05) and their oxidative stability. Covalently crosslinking phenolic compounds to proteins is a better method to prepare stable emulsions. It is more prominent that TA shows a more significant improvement in emulsion stability due to the number of hydroxyl groups it can provide. This research might serve as a theoretical foundation for enhancing the quality of pine nut oil-related products. © 2022 Society of Chemical Industry.

Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar-Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide, p-aminobenzoic acid, NAD, NADH, uridine 5'-monophosphate, adenosine monophosphate, and methylmalonic acid. Collectively, these findings suggest that ABE may play a role in affecting oxidative stress and purine, nicotinate, and nicotinamide metabolism.

Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.

Oncogenic activation of the mTOR signaling pathway occurs frequently in tumor cells and contributes to the devastating features of cancer, including breast cancer. mTOR inhibitors rapalogs are promising anticancer agents in clinical trials; however, rapalogs resistance remains an unresolved clinical challenge. Therefore, understanding the mechanisms by which cells become resistant to rapalogs may guide the development of successful mTOR-targeted cancer therapy. In this study, we found that eEF-2K, which is overexpressed in cancer cells and is required for survival of stressed cells, was involved in the negative-feedback activation of Akt and cytoprotective autophagy induction in breast cancer cells in response to mTOR inhibitors. Therefore, disruption of eEF-2K simultaneously abrogates the two critical resistance signaling pathways, sensitizing breast cancer cells to rapalogs. Importantly, we identified mitoxantrone, an admitted anticancer drug for a wide range of tumors, as a potential inhibitor of eEF-2K via a structure-based virtual screening strategy. We further demonstrated that mitoxantrone binds to eEF-2K and inhibits its activity, and the combination treatment of mitoxantrone and mTOR inhibitor resulted in significant synergistic cytotoxicity in breast cancer. In conclusion, we report that eEF-2K contributes to the activation of resistance signaling pathways of mTOR inhibitor, suggesting a novel strategy to enhance mTOR-targeted cancer therapy through combining mitoxantrone, an eEF-2K inhibitor.

Dietary preferences were closely associated with the pathogenesis of numbers of metabolic disorders, in particularly, obesity. Dietary fiber was shown to be capable of preventing weight gain and excessive food intake mainly through stimulating chewing and saliva secretion, and promote satiety signals. In this study, we characterized the "Vitamin World® Vegan Meal" Formula of Feihe, a novel protein‐enriched fiber dietary supplement contained potato protease inhibitor II (PI2) that developed. And we demonstrated that this particular fiber formula was effective in preventing weight gain, increasing satiety signals, and reducing food intake in rats in a dosage‐dependent manner. Our study provides lines of evidence and would further bolster the use of this nutritious vegan meal in regulating satiety and food intake in clinics., A novel protein‐enriched fiber dietary supplement contained potato protease inhibitor II was developed. The satiety function evaluation of the fiber vegan product was carried out.

Our recent study demonstrated eIF3a loss contributes to vemurafenib resistance in melanoma by activating ERK. However, overexpression of eIF3a in the clinic is not feasible to produce vemurafenib re-sensitization, and ERK inhibitors combined with vemurafenib still exhibit limited effectiveness in the treatment of melanoma. Here, using the human receptor tyrosine kinase phosphorylation antibody array, we observed that silencing eIF3a could activate BMX, a tyrosine kinase. The BMX inhibitor CHMFL-BMX-078 could significantly suppress proliferation and induce cell cycle arrest in vemurafenib resistant melanoma cell line A375 (A375R), however, it was hypotoxic in immortal keratinocytes, melanoma cells, and other solid cancer cells such as glioma and breast cancer cells. Furthermore, the combined treatment of CHMFL-BMX-078 and vemurafenib synergistically reduced cell viability and restored the sensitivity of resistant cells to vemurafenib. The reversal of the resistant phenotype by CHMFL-BMX-078 was associated with the AKT signaling pathway, as co-treatment with the AKT activator SC-79 or up-regulation of AKT attenuated the anti-proliferation effect of CHMFL-BMX-078 and vemurafenib. Lastly, we demonstrated that CHMFL-BMX-078 could significantly enhance vemurafenib efficacy in a xenograft model of A375R cells without producing additive toxicity. In conclusion, these findings reveal that the BMX inhibitor CHMFL-BMX-078 may reverse vemurafenib resistance in melanoma by suppressing the AKT signaling pathway, implying that CHMFL-BMX-078 may be a promising compound for overcoming vemurafenib resistance.

It has been realized that FDA approved drugs may have more molecular targets than is commonly thought. Thus, to find the exact drug-target interactions (DTIs) is of great significance for exploring the new molecular mechanism of drugs. Here, we developed a multi-scale system pharmacology (MSSP) method for the large-scale prediction of DTIs. We used MSSP to integrate drug-related and target-related data from multiple levels, the network structural data formed by known drug-target relationships for predicting likely unknown DTIs. Prediction results revealed that Ixabepilone, an epothilone B analog for treating breast cancer patients, may target Bcl-2, an oncogene that contributes to tumor progression and therapy resistance by inhibiting apoptosis. Furthermore, we demonstrated that Ixabepilone could bind with Bcl-2 and decrease its protein expression in breast cancer cells. The down-regulation of Bcl-2 by Ixabepilone is resulted from promoting its degradation by affecting p-Bcl-2. We further found that Ixabepilone could induce autophagy by releasing Beclin1 from Beclin1/Bcl-2 complex. Inhibition of autophagy by knockdown of Beclin1 or pharmacological inhibitor augmented apoptosis, thus enhancing the antitumor efficacy of Ixabepilone against breast cancer cells in vitro and in vivo. In addition, Ixabepilone also decreases Bcl-2 protein expression and induces cytoprotective autophagy in human hepatic carcinoma and glioma cells. In conclusion, this study not only provides a feasible and alternative way exploring new molecular mechanisms of drugs by combing computation DTI prediction, but also reveals an effective strategy to reinforce the antitumor efficacy of Ixabepilone.

Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2–8 μmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231. Furthermore, the Akt-mTOR-eEF-2K signaling pathway was demonstrated to be involved in RA-induced activation of autophagy in the 3 breast cancer cell lines. Treatment with RA (2–10 μmol/L) dose-dependently induced apoptosis in the 3 breast cancer cell lines. Pretreatment with the autophagy inhibitor chloroquine (CQ, 20 μmol/L) significantly enhanced RA-caused cytotoxicity via promoting apoptosis. In conclusion, our results suggest that modulating autophagy can reinforce the cytotoxicity of RA against human breast cancer cells.

Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar-Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide

Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells. Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), was identified as a potent activator of autophagy. The activation of autophagy by TBMS1 was evidenced by increased LC3-II amount and GFP-LC3 dots, observation of autophagosomes under electron microscopy, and enhanced autophagic flux. To explore the mechanisms underlying TBMS1-activated autophagy, we performed cheminformatic analyses and surface plasmon resonance (SPR) binding assay that showed a higher likelihood of the binding between Akt protein and TBMS1. In three human breast cancer cell lines, we demonstrated that Akt–mTOR–eEF-2K pathway was involved in TBMS1-induced activation of autophagy, while Akt-mediated downregulations of Mcl-1, Bcl-xl, and Bcl-2 led to the activation of apoptosis of the breast cancer cells. Inhibition of autophagy enhanced the cytotoxic effect of TBMS1 via promoting apoptosis. Our results demonstrate the role and mechanism of TBMS1 in activating autophagy, suggesting that inhibition of cytoprotective autophagy may act as a therapeutic strategy to reinforce the activity of TBMS1 against cancers.

The industry cluster is an inevitable stage in the development of a regional industry and also a effective way to enhance the industrial competitiveness of a region.The textile and garment industry, as a traditional industry in Shanghai ,is facing a stage of further development of industrial clusters,In this paper,we talk about the status quo of Shanghai textile and garment industry cluster analysis, the development trends and the development of countermeasures discussed.

In order to improve trajectory tracking accuracy for a redundantly actuated parallel manipulator, a so-called augmented nonlinear PD (ANPD) controller based on the conventional dynamic controller is proposed in this paper. The ANPD controller is designed by replacing the linear PD in the augmented PD controller with a nonlinear PD algorithm. The stability of the parallel manipulator system with the proposed ANPD controller is proven using the Lyapunov stability theorem, and the ANPD controller is further proven to guarantee asymptotic convergence to zero of both the tracking error and error rate. The superiority of the ANPD controller is verified through trajectory tracking experiments of an actual 2-d.o.f. redundantly actuated parallel manipulator.