Preparation and functional properties of rice bran globulin-chitooligosaccharide-quercetin-resveratrol covalent complex.

BACKGROUND: As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. RESULTS: A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. CONCLUSION: The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.

17ß-Estradiol promotes metastasis in triple-negative breast cancer through the Calpain/YAP/ß-catenin signaling axis.

ß-catenin is an important regulator of malignant progression. 17ß-Estradiol (E2), an important sex hormone in women, promotes the growth and metastasis of triple-negative breast cancer (TNBC). However, whether ß-catenin is involved in E2-induced metastasis of TNBC remains unknown. In this study, we show that E2 induces the proliferation, migration, invasion, and metastasis of TNBC cells. E2 induces ß-catenin protein expression and nuclear translocation, thereby regulating the expression of target genes such as Cyclin D1 and MMP-9. The inhibition of ß-catenin reversed the E2-induced cell malignant behaviors. Additionally, E2 activated Calpain by increasing intracellular Ca2+ levels and reducing calpastatin levels. When Calpain was inhibited, E2 did not induce the proliferation, migration, invasion, or metastasis of TNBC cells. In addition, E2 promoted translocation of YAP into the nucleus by inhibiting its phosphorylation. Calpain inhibition reversed the E2-induced YAP dephosphorylation. Inhibition of YAP transcriptional activity reversed the effects of E2 on the proliferation, migration, invasion, and ß-catenin of TNBC cells. In conclusion, we demonstrated that E2 induced metastasis-related behaviors in TNBC cells and this effect was mediated through the Calpain/YAP/ß-catenin signaling pathway.

Restoration of Cullin3 gene expression enhances the improved effects of sonic hedgehog signaling activation for hypertension and attenuates the dysfunction of vascular smooth muscle cells.

BACKGROUND: Hypertension is known as a major factor for global mortality. We aimed to investigate the role of Cullin3 (CUL3) in the regulation of hypertension. MATERIAL AND METHODS: Human vascular smooth muscle cells (VSMCs) were treated with Angiotensin II (Ang II) to establish a hypertension in vitro model. Cell viability was detected by a cell counting kit-8 (CCK-8) assay. The content of reactive oxygen species (ROS) was evaluated by kit. Transwell assay and TUNEL staining were, respectively, used to assess cell migration and apoptosis. Additionally, the expression of sonic hedgehog (SHH) signaling-related proteins (SHH, smoothened homolog (Smo) and glioblastoma (Gli)) and CUL3 was tested with western blotting. Following treatment with Cyclopamine (Cycl), an inhibitor of SHH signaling, in Ang II-induced VSMCs, cell viability, migration, apoptosis and ROS content were determined again. Then, VSMCs were transfected with CUL3 plasmid or/and treated with sonic hedgehog signaling agonist (SAG) to explore the impacts on Ang II-induced VSMCs damage. In vivo, a hypertensive mouse model was established. Systolic blood pressure and diastolic blood pressure were determined. The histopathologic changes of abdominal aortic tissues were examined using H&E staining. The expression of SHH, Smo, Gli and CUL3 was tested with western blotting. RESULTS: Significantly increased proliferation, migration and apoptosis of VSMCs were observed after Ang II exposure. Moreover, Ang II induced upregulated SHH, Smo and Gli expression, whereas limited increase in CUL3 expression was observed. The content of ROS in Ang II-stimulated VSMCs presented the same results. Following Cycl treatment, the high levels of proliferation and migration in Ang II-treated VSMCs were notably remedied while the apoptosis and ROS concentration were further increased. Moreover, Cycl downregulated SHH, Smo, Gli and CUL3 expression. Above-mentioned changes caused by Ang II were reversed following SAG addition. Indeed, SAG treatment combined with restoration of CUL3 expression inhibited proliferation, migration, apoptosis and ROS level in Ang II-stimulated VSMCs. In vivo, SAG aggravated the histopathological changes of the aorta and with a worse tendency after both SAG intervention and CUL3 silencing. By contrast, SAG treatment and rebound in CUL3 expression alleviated the vascular damage. CONCLUSIONS: Collectively, restoration of CUL3 gene expression protected against hypertension through enhancing the effects of SHH activation in inhibition of apoptosis and oxidative stress for hypertension and alleviating the dysfunction of VSMCs.

Association of gut microbiota characteristics and metabolites reveals the regulation mechanisms under cadmium consumption circumstance.

BACKGROUND: Cadmium is a non-biodegradable heavy metal with a long biological half-life. Although its negative impact on human health has been previously reported, the association of cadmium consumption overdose with changes in the gut microbiota and its corresponding metabolites has not been fully elucidated so far. RESULTS: Cadmium consumption overdose led to a reduced body weight gain accompanied by an enhanced level of the proinflammatory cytokine tumor necrosis factor-α, interleukin-6, and histamine in the serum of the rats in comparison with normal rats. Furthermore, hepatotoxicity was also observed to be induced by cadmium, which was consistent with abnormal hepatic activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and oxidative stress. In contrast, Lactobacillus rhamnosus-fermented Ganoderma lucidum (FGL) slice supplementation improved the aforementioned physiological properties. More importantly, microbiome and metabolites analysis indicated cadmium exposure significantly reduced the generation of short-chain fatty acids in the gut, particularly butyrate. However, rats in the FGL group had the highest level of butyrate in the feces, characterized with significantly enriched probiotics (Lactobacillus, Bifidobacterium) and butyrate-producing bacteria (Roseburia). CONCLUSION: The targeted regulation of the gut microbial community and its metabolites might be the essential association for attenuating body dysfunction induced by cadmium. The supplementation of FGL, as evidenced in this study, might highlight a novel approach to this field. © 2022 Society of Chemical Industry.

Fabrication, structure, and function evaluation of the ferritin based nano-carrier for food bioactive compounds.

The low solubility, instability, and low bioavailability of food bioactive compounds such as polyphenols and flavonoids, restrict their applications in the fields of food science and nutrition. Ferritin protein has received more and more attention in encapsulation and delivery of the bioactive compounds due to its nanosized shell-like structure and its reversible self-assembly character. After encapsulation, bioactive compounds can be functionalized by the ferritin vehicle to achieve stabilization, solubilization, and targeted delivery. In addition, the outer interfaces and the porous structure of ferritin are also artfully harnessed for encapsulation. This review focuses on the newest advances in the fabrication, characterization, and application of ferritin-based nano-carriers for bioactive compounds by the reversible self-assembly, outer-interface decoration methods, and the channel-directed approach. The functional improvements of food bioactive compounds, including their solubility, stability, and cellular uptake, are emphasized. The limitations that affect ferritin encapsulation are also examined.

Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease that causes excessive hepatic lipid accumulation. Reducing hepatic lipid deposition is a key issue in treatment and inhibition of NAFLD evolution. Silymarin is a potent hepatoprotective agent; however, it has low oral bioavailability due to its poor aqueous solubility and low membrane permeability. Unfortunately, few studies have addressed the development of convenient oral nanocarriers that can efficiently deliver silymarin to the liver and enhance its lipid-lowering effect. We designed silymarin-loaded lipid polymer hybrid nanoparticles containing chitosan (CS-LPNs) to improve silymarin bioavailability and evaluated their lipid-lowering effect in adiponutrin/patatin-like phospholipase-3 I148M transgenic mice, an NAFLD model. RESULTS: Compared to chitosan-free nanoparticles, CS-LPNs showed 1.92-fold higher uptake by fatty liver cells. Additionally, CS-LPNs significantly reduced TG levels in fatty liver cells in an in vitro lipid deposition assay, suggesting their potential lipid-lowering effects. The oral bioavailability of silymarin from CS-LPNs was 14.38-fold higher than that from suspensions in rats. Moreover, compared with chitosan-free nanoparticles, CS-LPNs effectively reduced blood lipid levels (TG), improved liver function (AST and ALT), and reduced lipid accumulation in the livers of mice in vivo. Reduced macrovesicular steatosis in pathological tissue after CS-LPN treatment indicated their protective effect against liver steatosis in NAFLD. CONCLUSIONS: CS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model. These findings suggest that CS-LPNs may be a promising oral nanocarrier for NAFLD therapeutics.

Mucosal transfer of wheat germ agglutinin modified lipid-polymer hybrid nanoparticles for oral delivery of oridonin.

Wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles (WGA-LPNs) promote cellular uptake after oral delivery via receptor-mediated endocytosis and bioadhesion. Understanding the mucosal transport of WGA-LPNs would help to improve bioavailability and ensure therapeutic efficacy. In this study, WGA-LPNs interacted with mucin, forming larger agglomerates with intact core-shell structure. The interaction of WGA-LPNs with mucin improved enterocyte endocytosis in Caco-2 cells. An in situ intestinal diffusion study in mice confirmed that WGA-LPNs reached enterocytes and underwent endocytosis, despite interference from mucin. Importantly, oral bioavailability of oridonin-loaded WGA-LPNs increased by 1.96-fold compared with that of LPNs. Furthermore, oral administration of WGA-LPNs inhibited tumor growth in HepG2 xenograft nude mice. In addition to elucidating interactions between WGA-LPNs and mucin, these results indicated that WGA-LPNs might act as promising nanocarriers for oral delivery of drugs.

Molecular biological characteristics based Hierarchical Mumford-Shah Vector-Model for the delineation of biological target volumes corresponding to head and neck tumors.

To more accurately and precisely delineate a biologic target volume (BTV) for the positron emission tomography (PET)-guided radiotherapy treatment planning, we proposed a novel Hierarchical Mumford-Shah Vector Model (HMSMv), where the image-vector was composed of the molecular biological characteristics such as contrast, busyness and the standard uptake value (SUV) of tumors. The BTV was delineated via the propagation of the level set flow of the proposed HMSMv. The propagation took place inside a ring-volume of interest (VOI) which was defined by an adaptive volume-growing algorithm based on the PET SUV, contrast and busyness of a tumor. Four patient studies were assessed and visually inspected by two radiation oncologists (Suyu Zhu and Zaijie Huang). Compared the resulting BTV with the gross target volume (GTV) of one patient study, the sensitivity, specificity and similarity were 92.28%, 87.29%, 79.28% respectively. Moreover, all of four BTVs were between the corresponding GTV and planning target volume (PTV). Most of the BTVs were between the GTV and the clinical target volume (CTV). The results demonstrated that the proposed method can delineate the BTVs of nasopharyngeal carcinomas more accurately and precisely than the manual delineation and also the threshold segmentation method with SUV of 2.5 as the threshold. The GTV, CTV, and PTV were manually delineated by the two radiation oncologists based on PET, CT and MRI images for the intensity modulated radiotherapy (IMRT) planning of the four patients.

Silicon attenuates cadmium toxicity in Solanum nigrum L. by reducing cadmium uptake and oxidative stress.

Solanum nigrum L. is considered to be a potential plant for restoring Cd-contaminated soils. Si could enhance plants tolerance to heavy metal; however, the mechanism of Si-mediated alleviation of Cd toxicity in S. nigrum was not clear. Three-week-old S. nigrum seedlings were grown in Hoagland solution containing 0 or 100 µM Cd with or without 1 mM Si for 4 days. The results showed that the Cd concentration both in roots and shoots of Si-supplied plant was significantly reduced, especially in expanding and old leaves. The relative proportion of ethanol-extractable Cd, water-extractable Cd and NaCl-extractable Cd in roots was increased by adding Si, while the root-to-shoot Cd translocation was not decreased. Furthermore, in comparison with single Cd treatment, supplying Si could reduce H2O2 accumulation and cell death in roots, and the electrolyte leakage and H2O2 concentration in functional leaves. Moreover, the activity of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7) and ascorbate peroxidase (APX, EC 1.11.1.11) in functional leaves was markedly increased by Cd exposure, while the antioxidative enzyme activities in Cd plus Si treatment seedlings were significantly lower than that in Cd treatment alone, this decrease might be attributed to the reduction of Cd concentration and Cd-induced oxidative damages. These results demonstrate that Si-enhanced Cd tolerance in S. nigrum is mainly due to the decrease of Cd uptake in roots and Cd distribution in expanding and old leaves, as well as lowering oxidative stress induced by Cd in plants.

[Antioxidative enzymes play key roles in cadmium tolerance of Phytolacca americana].

Phytolacca americana L. has the capacity to take up and accumulate to very high levels heavy metals such as Mn and Cd, and is used for phytoextraction of heavy metal contaminated soils. The role of antioxidative enzyme of Phytolacca americana in response to Cd stress is unknown. The 6-week-old seedlings of Phytolacca americana were exposed to half strength Hoagland solution with 200 micromol/L CdCl2 or 400 micromol/L CdCl2 for 4 days. The content of H2O2 and MDA, and electrolyte leakage increased, while the photosynthetic rate decreased, indicated that the oxidative damage induced by Cd stress in Phytolacca americana was one of the metal toxicity mechanism. The activities of SOD and POD increased rapidly with elevated Cd concentration and exposure time, CAT activity was stable in response to 200 micromol/L CdCl2 stress, and increased only at 3 d later upon 400 micromol/L CdCl2, treatment. Suggested that the enzymatic antioxidation capacity played important role in Cd tolerance of hyperaccumulator plant.