Whey protein and flaxseed gum co-encapsulated fucoxanthin promoted tumor cells apoptosis based on MAPK-PI3K/Akt regulation on Huh-7 cell xenografted nude mice.

Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg-1) and doxorubicin hydrochloride (DOX, 1 mg kg-1) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ±â€¯1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis.

Phycocyanin-phlorotannin complexes improve the structure and functional properties of yogurt.

Adding natural bioactive ingredients to yogurt can improve the nutritional and physiological benefits. In this study, we used ultrasonic-assisted phlorotannin from Ascophyllum nodosum (A. nodosum) modified phycocyanin (PC) to form a complex (UPP) to produce a fortified fermented yogurt. The effects of PC and UPP on the structure, stability, and function of fermented yogurt within 7 days were assessed using physicochemical properties, texture analysis, rheological testing, 16S rDNA sequencing analysis, and lipidomics analysis. Molecular docking indicated that PC might bind to phlorotannin via ARG-77, ARG-84, LEU-120, ALA-81, CYS-82, and ASP-85 sites.When the mass ratio of the complex is 1:1, the ability of UPP1:1 to remove DPPH· scavenging ability in an acid environment increased by about 50 %. UPP1:1 with more acid stability changed the microstructure of the yogurt, enhanced the stability of the yogurt, improved the antioxidant properties, and inhibited the growth of harmful bacteria within 7 days. This work encouraged the extraction and use of phlorotannin from edible brown algae and offered a straightforward method for making yogurt supplemented with PC.

Characterization of flavor substances in cooking and seasoned cooking brown seaweeds by GC-IMS and E-nose.

The flavor of algae was one of the key factors for consumer acceptance. The objective of this study was to investigate the characteristic volatile compounds in cooking and seasoned cooking edible brown seaweeds (Undaria pinnatifida and Laminaria japonica). The gas chromatography-ion mobility spectrometry (GC-IMS) and electronic nose (E-nose) analysis showed that baking resulted in significant difference in flavor of brown seaweeds. However, the overall effect of cooking was not as significant as that of the seasoning solution treatment. Additionally, brown seaweeds treated with the seasoning solution were more acceptable. Undaria pinnatifida was found to contain 72 volatile flavor compounds, while Laminaria japonica had a total of 70. This study proved the applicability of GC-IMS combined with E-nose technology to detect the changes of volatile components of brown seaweeds after processing, providing beneficial knowledge and basic theory for the deep processing of brown seaweeds.

Undaria pinnatifida gel inks for food 3D printing are developed based on the colloidal properties of Undaria pinnatifida slurry and protein/colloidal/starch substances.

Currently, people eat Undaria pinnatifida (UP) in a single way, and processing homogeneity is serious. However, UP has not gained any traction in the 3D printing industry to date. This study explored the incorporation of soy protein isolate (SPI), pea protein (PP), xanthan gum (XG), guar gum (GG), corn starch (CS), and potato starch (PS) into UP slurry liquid, the primary component of the study, to formulate a UP gel ink. The UP gel 3D printing ink system based on UP paste was established and characterized. The results show that hydrogen bonds are formed, and three-dimensional gel network structure is formed in all UP gel inks. UP gel inks containing high concentrations of SPI and GG exhibited good texture and rheological qualities and good 3D printing effect, with storage modulus (G') values of 8440.405 ± 3.893 and 8111.730 ± 3.585 Pa. The loss of modulus (G″) values were 1409.107 ± 3.524 and 1071.673 ± 3.669 Pa. Unfortunately, the properties of other UP gel inks are not suitable, resulting in poor 3D printing results. The food 3D printing method developed in this study provides valuable insights for expanding food 3D printing material choices and achieving high-value applications of UP.

Baicalin attenuates chronic unpredictable mild stress-induced hippocampal neuronal apoptosis through regulating SIRT1/PARP1 signaling pathway.

Baicalin (BA), a flavonoid glycoside extracts from Scutellaria baicalensis Georgi, has been reported to exert antidepressant effects. Emerging evidence indicates that neuronal apoptosis plays a crucial role in the pathogenesis of depression. Poly (ADP-ribose) polymerase-1 (PARP1) is established as a key regulator of the cellular apoptosis. In the present study, we explored whether BA exerts antidepressant effects by regulating PARP1 signaling pathway and elucidated the underlying mechanisms. We found that administration of BA (30 mg/kg, 60 mg/kg) alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors by increasing sucrose consumption in sucrose preference test (SPT), improving activity status in open field test (OFT) and reducing rest time in tail suspension test (TST). Hematoxylin and eosin (HE) staining and Nissl staining showed that BA ameliorated CUMS-induced neuronal damage in the hippocampus. Moreover, BA significantly upregulated anti-apoptotic protein Bcl-2, downregulated pro-apoptotic protein Bax and cleaved-caspase-3 after CUMS in hippocampal of mice. Intriguingly, western blot and immunohistochemistry (IHC) results showed that the protein level of PARP1 was significantly increased in hippocampal tissue after CUMS, which was reversed by BA treatment. In primary hippocampal neurons (PHNs), BA abrogated the neuronal apoptosis caused by PARP1 overexpression. Meanwhile, BA significantly increased the protein level of SIRT1, SIRT1 inhibitor (EX-527) treatment reversed the effect of BA on reducing the protein level of PARP1 and neuronal apoptosis in CUMS-induced mice. Overall, our results indicated that BA attenuated the CUMS-induced hippocampal neuronal apoptosis through regulating the SIRT1/PARP1 signaling pathway.

Computational insights into the interaction mechanism of transcription cofactor vestigial-like protein 4 binding to TEA domain transcription factor 4 by molecular dynamics simulation and molecular mechanics generalized Born/surface area) calculation.

Hippo pathway has been implicated in the suppression of tissue overgrowth and tumor formation by restricting the oncogenic activity of Yes-associated protein (YAP). Transcription cofactor vestigial-like protein 4 (VGLL4), a natural YAP antagonist that competes with YAP for TEA domain transcription factor 4 (TEAD4) binding is a potential tumor suppressor in human gastric cancer. Comparing with the full length of VGLL4, the Tondu 2 domain of VGLL4 alone is fully functional in inhibiting YAP-induced TEAD4 reporter activity. Revealing the details of binding interaction between VGLL4 and TEAD4 would accelerate the discovery of improved drugs against YAP-driven human cancers. We investigated systematically the interaction mechanisms between TEAD4 and VGLL4 by molecular dynamics (MD) simulation, free energy calculation, and free energy decomposition analysis. Our simulations show that two loops of VGLL4 (residues 218-222 and 251-252) have little binding contribution on VGLL4 binding to TEAD4. The ß1 strand of VGLL4 plays important role in the contribution to the binding, whereas the α3 helix gives small contribution. More interestingly, the mutation of several residues of α2 helix to alanine results in the contribution of α2 helix decreasing, accompanied by the increased binding contribution of α3 helix. Deletion of the ß1 or α3 segment of VGLL4 has slight effect on the remaining two segments. Our simulation is well consistent with the in vivo evaluation of the binding of biotinylated VGLL4 peptides to TEAD4 in HepG2 cells by immunological approaches. We expect this work can provide valuable information for design of improved VGLL4 derivative anticancer peptides. Communicated by Ramaswamy H. Sarma.

Synthesis and biological evaluation of bifendate derivatives bearing 6,7-dihydro-dibenzo[c,e]azepine scaffold as potential P-glycoprotein and tumor metastasis inhibitors.

As a continuation of previous research, fifteen bifendate derivatives bearing 6,7-dihydro-dibenzo [c,e]azepine scaffold were synthesized and evaluated as P-gp-medicated multidrug resistance (MDR) reversal agents. Biological evaluation indicated that compounds 6k and 9c more potently reversed P-gp-mediated MDR than bifendate and verapamil (VRP) by blocking P-gp mediated drug efflux function and not by decreasing P-gp expression in K562/A02 MDR cells. Interestingly, wound-healing and chamber migration assay showed that 6k and 9c could significantly attenuate the migration of MDA-MB-231 cells. Notably, 6k and 9c could markedly suppress the invasive activity of MDA-MB-231 cells, thus displayed potential anti-metastasis activity. Preliminary mechanism studies indicated that the anti-metastasis activity of 6k and 9c was associated with their inhibitory effect on the activity and expression of MMP-2 and MMP-9. These results, together with the MDR reversal results indicated that compounds 6k and 9c might be promising leads for developing novel anti-cancer agents with P-gp and tumor metastasis inhibitory activities.

LFG-500, a novel synthetic flavonoid, suppresses epithelial-mesenchymal transition in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment.

Increasing evidence indicates that inflammatory microenvironment facilitates tumor metastasis. Here, we found that LFG-500, a novel synthetic flavonoid, significantly inhibited epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma A549 and H1299 cells co-cultured with LPS-challenged THP-1 cells or cultured in THP-1 cell-derived conditioned medium. Moreover, we found that TNF-α is a direct and decisive factor for promoting EMT and LFG-500 suppressed TNF-α-induced EMT and cell motility. NLRP3 knockdown inactivated NLRP3 inflammasome, which subsequently inhibited EMT and blocked cell migration, indicating that TNF-α-induced EMT requires the NLRP3 inflammasome. LFG-500 inhibited the activation of the NLRP3 inflammasome, thus inhibiting EMT. Moreover, LFG-500 treatment significantly inhibited metastasis in vivo by downregulating NLRP3 expression. Importantly, we found that NLRP3 was highly expressed in high-grade lung adenocarcinoma and that its expression was correlated with lymph node metastasis. NLRP3 and vimentin levels were significantly increased in matched metastatic lymph nodes. Moreover, a significant positive correlation was observed between their levels. Together, these results suggest that LFG-500 markedly suppresses EMT by inhibiting the NLRP3 inflammasome in the inflammatory microenvironment and that NLRP3 is a potential biomarker of lung adenocarcinoma metastasis.

Apoptosis induction is involved in UVA-induced autolysis in sea cucumber Stichopus japonicus.

Autolysis easily happens to sea cucumber (Stichopus japonicus, S. japonicus) for external stimulus like UV exposure causing heavy economic losses. Therefore, it is meaningful to reveal the mechanism of S. japonicas autolysis. In the present study, to examine the involvement of apoptosis induction in UVA-induced autolysis of S. japonicas, we investigated the biochemical events including the DNA fragmentation, caspase-3 activation, mitogen-activated protein kinases (MAPKs) phosphorylation and free radical formation. Substantial morphological changes such as intestine vomiting and dermatolysis were observed in S. japonicus during the incubation after 1-h UVA irradiation (10W/m(2)). The degradation of the structural proteins and enhancement of cathepsin L activity were also detected, suggesting the profound impact of proteolysis caused by the UVA irradiation even for 1h. Furthermore, the DNA fragmentation and specific activity of caspase-3 was increased up to 12h after UVA irradiation. The levels of phosphorylated p38 mitogen activated protein kinase (MAPK) and phosphorylated c-Jun.-N-terminal kinase (JNK) were significantly increased by the UVA irradiation for 1h. An electron spin resonance (ESR) analysis revealed that UVA enhanced the free radical formation in S. japonicas, even through we could not identify the attributed species. These results suggest that UVA-induced autolysis in S. japonicas at least partially involves the oxidative stress-sensitive apoptosis induction pathway. These data present a novel insight into the mechanisms of sea cucumber autolysis induced by external stress.

ROS production in homogenate from the body wall of sea cucumber Stichopus japonicus under UVA irradiation: ESR spin-trapping study.

Sea cucumber Stichopus japonicus (S. japonicus) shows a strong ability of autolysis, which leads to severe deterioration in sea cucumber quality during processing and storage. In this study, to further characterize the mechanism of sea cucumber autolysis, hydroxyl radical production induced by ultraviolet A (UVA) irradiation was investigated. Homogenate from the body wall of S. japonicas was prepared and subjected to UVA irradiation at room temperature. Electron Spin Resonance (ESR) spectra of the treated samples were subsequently recorded. The results showed that hydroxyl radicals (OH) became more abundant while the time of UVA treatment and the homogenate concentration were increased. Addition of superoxide dismutase (SOD), catalase, EDTA, desferal, NaN3 and D2O to the homogenate samples led to different degrees of inhibition on OH production. Metal cations and pH also showed different effects on OH production. These results indicated that OH was produced in the homogenate with a possible pathway as follows: O2(-) → H2O2 → OH, suggesting that OH might be a critical factor in UVA-induced S. japonicus autolysis.