Enhancing vitamin D3 bioaccessibility: Unveiling hydrophobic interactions in soybean protein isolate and vitamin D3 binding via an infant in vitro digestion model.

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D3 (VD3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (Ka = 0.166 × 105 L·mol-1) at 80 MPa and significant surface hydrophobicity (H0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD3 bioavailability. This investigation underscores the potential of SPI-VD3 nanoparticles in bolstering VD3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations.

Synthesis and anti-inflammatory activity of mogrol derivatives modified at C24 site.

Mogrol, the aglycone of well-known sweeter mogrosides, shows potent anti-inflammatory activity. In this study, forty-two mogrol derivatives bearing various pharmacophores with oxygen or nitrogen atoms were designed and synthesized via structural modification at C24 site, and their anti-inflammatory activity were screened against lipopolysaccharide (LPS)-induced RAW264.7 cells. Compared with mogrol, most of derivatives exhibited stronger inhibition of NO production without cytotoxicity. In particular, compound B5 that contained an indole motif effectively suppressed the secretion of inflammatory mediators including TNF-α and IL-6, and inhibited the expression levels of TLR4, p-p65 and iNOS proteins. Molecular docking showed that the active B5 interacted with amino acid residues of iNOS protein through π-π stacking and hydrophobic interactions with binding affinity value of -12.1 kcal/mol, which was much stronger than mogrol (-8.9 kcal/mol). These results suggest that derivative B5 is a promising anti-inflammatory molecule and the strategy of hybridizing indole skeleton on mogrol is worthy for further attention.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B.

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Metabolism of Two Mogroside Isomers, Mogroside III and Mogroside IIIE, in Normal and Drug-Metabolizing Enzyme-Induced Rats.

Mogrosides III (1) and IIIE (2) are two important bioactive cucurbitane-type triterpenoid triglycosides in the edible fruits of Siraitia grosvenorii (Swingle), which are isomers and have only a minor difference in their structures. To clarify the effects of structural difference and drug-metabolizing-enzyme induction on their metabolism in vivo, their metabolites in normal rats and drug-metabolizing-enzyme-induced rats were tentatively identified and semiquantified by using the HPLC-DAD-ESI-IT-TOF-MSn technique. Totally, 76, 78, 96, and 121 metabolites of mogrosides were identified in the NIII (normal rats orally administered with mogroside III), NIIIE (normal rats orally administered with mogroside IIIE), EIII (drug-metabolizing-enzyme-induced rats orally administered with mogroside III), and EIIIE (drug-metabolizing-enzyme-induced rats orally administered with mogroside IIIE) groups, respectively. The metabolite differences among these groups indicated that their minor structural differences are responsible for the significant differences in their metabolites, and the induction of drug-metabolizing enzymes significantly increased the number of their metabolites. These findings would improve our understanding of the in vivo processes of mogrosides III and IIIE as well as their interactions with other food bioactive components or drugs.

The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

Identification and Isolation of α-Glucosidase Inhibitors from Siraitia grosvenorii Roots Using Bio-Affinity Ultrafiltration and Comprehensive Chromatography.

The discovery of bioactive compounds from medicinal plants has played a crucial role in drug discovery. In this study, a simple and efficient method utilizing affinity-based ultrafiltration (UF) coupled with high-performance liquid chromatography (HPLC) was developed for the rapid screening and targeted separation of α-glucosidase inhibitors from Siraitia grosvenorii roots. First, an active fraction of S. grosvenorii roots (SGR2) was prepared, and 17 potential α-glucosidase inhibitors were identified based on UF-HPLC analysis. Second, guided by UF-HPLC, a combination of MCI gel CHP-20P column chromatography, high-speed counter-current countercurrent chromatography, and preparative HPLC were conducted to isolate the compounds producing active peaks. Sixteen compounds were successfully isolated from SGR2, including two lignans and fourteen cucurbitane-type triterpenoids. The structures of the novel compounds (4, 6, 7, 8, 9, and 11) were elucidated using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry. Finally, the α-glucosidase inhibitory activities of the isolated compounds were verified via enzyme inhibition assays and molecular docking analysis, all of which were found to exhibit certain inhibitory activity. Compound 14 exhibited the strongest inhibitory activity, with an IC50 value of 430.13 ± 13.33 µM, which was superior to that of acarbose (1332.50 ± 58.53 µM). The relationships between the structures of the compounds and their inhibitory activities were also investigated. Molecular docking showed that the highly active inhibitors interacted with α-glucosidase through hydrogen bonds and hydrophobic interactions. Our results demonstrate the beneficial effects of S. grosvenorii roots and their constituents on α-glucosidase inhibition.

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study.

Background: The issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Methods: We applied two-sample Mendelian randomization to investigate relationships with gastrointestinal disorders. We obtained genome-wide association study (GWAS) summary data of any stroke, ischemic stroke, and its subtypes from the MEGASTROKE consortium. From the International Stroke Genetics Consortium (ISGC) meta-analysis, we acquired GWAS summary information on intracerebral hemorrhage (ICH), including all ICH, deep ICH, and lobar ICH. Several sensitivity studies were performed to identify heterogeneity and pleiotropy, while inverse-variance weighted (IVW) was utilized as the most dominant estimate. Results: No evidence for an effect of genetic predisposition to ischemic stroke and its subtypes on gastrointestinal disorders were found in IVW. The complications of deep ICH are a higher risk for PUD and GERD. Meanwhile, lobar ICH has a higher risk of complications for PUD. Conclusion: This study provides proof of the presence of a brain-gut axis. Among the complications of ICH, PUD and GERD were more common and associated with the site of hemorrhage.

Lindenane-Type Sesquiterpene Dimers Mitigate Lipopolysaccharide-Induced Inflammation by Inhibiting Toll-Like Receptor Signaling.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and trigger an inflammatory response via the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-ß (TRIF)-dependent pathways. Lindenane type sesquiterpene dimers (LSDs) are characteristic metabolites of plants belonging to the genus Sarcandra (Chloranthaceae). The aim of this study was to evaluate the potential anti-inflammatory effects of the LSDs shizukaol D (1) and sarcandrolide E (2) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages in vitro, and explore the underlying mechanisms. Both LSDs neutralized the LPS-induced morphological changes and production of nitric oxide (NO), as determined by CCK-8 assay and Griess assay, respectively. Furthermore, shizukaol D (1) and sarcandrolide E (2) downregulated interferon ß (IFNß), tumor necrosis factor α (TNFα) and interleukin-1ß (IL-1ß) mRNA levels as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibited the phosphorylation of nuclear factor kappa B p65 (p65), nuclear factor kappa-Bα (IκBα), Jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), mitogen-activated protein kinase p38 (p38), MyD88, IL-1RI-associated protein kinase 1 (IRAK1), and transforming growth factor-ß-activated kinase 1 (TAK1) proteins in the Western blotting assay. In conclusion, LSDs can alleviate the inflammatory response by inhibiting the TLR/MyD88 signalling pathway.

Design and synthesis of mogrol derivatives modified on a ring with anti-inflammatory and anti-proliferative activities.

A class of novel mogrol derivatives modified on A ring were synthesized. The screening result showed that indole-fused derivatives exhibited lower toxicity and better anti-inflammatory activity in LPS-induced RAW 264.7 cells model than mogrol and other compounds. Derivative B8 exerted superior inhibitory result of NO production (IC50 = 5.05 µM) and inhibitory ability of TNF-α and IL-6 secretion to mogrol through iNOS/NF-κB pathway. Besides, the CCK8 assay was performed to evaluate their anti-proliferative activity against non-small cell lung cancer including A549, NCI-H460, H1299 and H1975 cells. Compared with mogrol, compound B8 showed moderate anti-proliferative activities against A549 and H1975 cells, while derivatives bearing α, ß-unsaturated ketone scaffold displayed broad-spectrum growth inhibition against four cell lines. Among them, compound A9 showed 12-fold higher activity than mogrol against H1299 and H1975 cells. The suppressive effect on expression level of p-p65 might account for the compound A9-induced growth inhibition and cell cycle arrest at G1 phase.

Land Use and Climate Change Altered the Ecological Quality in the Luanhe River Basin.

Monitoring and assessing ecological quality (EQ) can help to understand the status and dynamics of the local ecosystem. Moreover, land use and climate change increase uncertainty in the ecosystem. The Luanhe River Basin (LHRB) is critical to the ecological security of the Beijing-Tianjin-Hebei region. To support ecosystem protection in the LHRB, we evaluated the EQ from 2001 to 2020 based on the Remote Sensing Ecological Index (RSEI) with the Google Earth Engine (GEE). Then, we introduced the coefficient of variation, Theil-Sen analysis, and Mann-Kendall test to quantify the variation and trend of the EQ. The results showed that the EQ in LHRB was relatively good, with 61.08% of the basin rated as 'good' or 'excellent'. The spatial distribution of EQ was low in the north and high in the middle, with strong improvement in the north and serious degradation in the south. The average EQ ranged from 0.58 to 0.64, showing a significant increasing trend. Furthermore, we found that the expansion of construction land has caused degradation of the EQ, whereas climate change likely improved the EQ in the upper and middle reaches of the LHRB. The results could help in understanding the state and trend of the eco-environment in the LHRB and support decision-making in land-use management and climate change.

Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy.

Purpose: To construct an immune-related gene prognostic index (IRGPI) for colon cancer and elucidate the molecular and immune characteristics as well as the benefit of immune checkpoint inhibitor (ICI) therapy in IRGPI-defined groups of colon cancer. Experimental Design: Transcriptional and clinical data of colon cancer samples were obtained from The Cancer Genome Atlas (TCGA) (n = 521). Immune-related genes were obtained from ImmPort and InnateDB databases. 21 immune-related hub genes were identified byweighted gene co-expression network analysis (WGCNA). the Cox regression method was used to construct IRGPI and validated with Gene Expression Omnibus (GEO) dataset (n = 584). Finally, the molecular and immune profiles in the groups defined by IRGPI and the benefit of ICI treatment were analyzed. Results: 8 genes were identified to construct IRGPI. IRGPI-low group had a better overall survival (OS) than IRGPI-high group. And this was well validated in the GEO cohort. Overall results showed that those with low IRGPI scores were enriched in antitumor metabolism, and collated with high infiltration of resting memory CD4 T cells and less aggressive phenotypes, benefiting more from ICI treatment. Conversely, high IRGPI scores were associated with cell adhesion molecules (CAMs) and chemokine signaling pathways, high infiltration of macrophage M1, suppressed immunity, more aggressive colon cancer phenotypes, as well as reduced therapeutic benefit from ICI treatment. Conclusions: IRGPI is a promising biomarker to differentiate the prognostic and molecular profile of colon cancer, as well as the therapeutic benefits of ICI treatment.

Synthesis and Antiproliferative Activity of Ester Derivatives of Mogrol through JAK2/STAT3 Pathway.

In attempt to enhance the antiproliferative activity of mogrol, two series of ester derivatives modified at C3 -OH and C11 -OH were designed and synthesized. The activity against human cancer cells including A549, NCI-H460 and CNE1 was screened by Cell Counting Kit-8 (CCK8) assay. According to the results, modifications of the mogrol core through introduction of different ester scaffolds drastically improved the cytotoxicity, and some of the derivatives exhibited even higher activity than the positive drug. Among them, compound M2h exhibited nearly 4 times more cytotoxic than 5-Fu against CNE1 cells, derivative M6c showed ten times higher activity with the IC50 value of 10.59 µM than mogrol against NCI-H460 cells, and compound M6a which contained one 1,2,3-triazole motif showed the strongest activity with an three folds lower IC50 value than mogrol. Furthermore, the most potent compound M2h could lead to cell cycle arrest at G2 phase on CNE1 cell lines and M6a induced G1 phase arrest on A549 cell lines. It was noteworthy that both M2h and M6a regulated signal transducer and activator of transcription 3 (STAT3) signal pathway through inhibiting phosphorylation of Janus Kinase 2 (JAK2) and STAT3, and simultaneously increasing the protein level of downstream cyclin p21.

Rhodomollosides A and B, glycosides of methyl everninate from the aerial parts of Rhododendron molle.

Two new glycosides of methyl everninate, rhodomollosides A (1) and B (2), were isolated from the aerial parts of a medicinal plant Rhododendron molle. The structures of 1 and 2 were elucidated on the basis of detailed spectroscopic analyses as well as HPLC analyses for thiazolidine derivatives of their sugar moieties. The sugar moiety of rhodomolloside A (1) was elucidated to be a rare monosaccharide, D-allose, while rhodomolloside B (2) was assigned as a D-glucoside of methyl everninate. Furthermore, they were evaluated for their cytotoxicity against RAW264.7 cells, and for their inhibitory effects with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7 cells model.

The spleen-strengthening and liver-draining herbal formula treatment of non-alcoholic fatty liver disease by regulation of intestinal flora in clinical trial.

Objective: As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and liver-draining formula (SLF) is a formula formed according to the theory of "One Qi Circulation" (Qing Dynasty, 1749) of Traditional Chinese Medicine (TCM), which has shown significant therapeutic effect in patients with NAFLD in a preliminary clinical observation. In this study, we aim to explore the mechanism of SLF against NAFLD, especially its effect on glucolipid metabolism, from the perspective of intestinal flora. Methods: A prospective, randomized, controlled clinical study was designed to observe the efficacy and safety of SLF in the treatment of NAFLD. The study participants were randomly and evenly divided into control group and treatment group (SLF group). The control group made lifestyle adjustments, while the SLF group was treated with SLF on top of the control group. Both groups were participated in the study for 12 consecutive weeks. Furthermore, the feces of the two groups were collected before and after treatment. The intestinal flora of each group and healthy control (HC) were detected utilizing 16S rRNA gene sequencing. Results: Compared with the control group, the SLF group showed significant improvements in liver function, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), meanwhile, patients had significantly lower lipid and homeostasis model assessment of insulin resistance (HOMA-IR) with better security. Intestinal flora 16S rRNA gene sequencing results indicated reduced flora diversity and altered species abundance in patients with NAFLD. At the phylum level, Desulfobacterota levels were reduced. Although Firmicutes and Bacteroidetes did not differ significantly between HC and NAFLD, when grouped by alanine transaminase (ALT) and aspartate transaminase (AST) levels in NAFLD, Firmicutes levels were significantly higher in patients with ALT or AST abnormalities, while Bacteroidetes was significantly lower. Clinical correlation analysis showed that Firmicutes positively correlated with gender, age, ALT, AST, LSM, and Fibroscan-AST (FAST) score, while the opposite was true for Bacteroidetes. At the genus level, the levels of Alistipes, Bilophila, Butyricimonas, Coprococcus, Lachnospiraceae_NK4A136 group Phascolarctobacterium, Ruminococcus, UCG-002, and UCG-003 were reduced, whereas abundance of Tyzzerella increased. There was no statistically significant difference in Firmicutes and Bacteroidota levels in the SLF group before and after treatment, but both bacteria tended to retrace. At the genus level, Coprococcus (Lachnospiraceae family), Lachnospiraceae_NK4A136 group (Lachnospiraceae family), and Ruminococcus (Ruminococcaceae family) were significantly higher in the SLF group after treatment, and there was also a tendency for Bilophila (Desulfovibrionaceae family) to be back-regulated toward HC. Conclusions: SLF can improve liver function and glucolipid metabolism in patients with NAFLD and lower down liver fat content to some extent. SLF could be carried out by regulating the disturbance of intestinal flora, especially Coprococcus, Lachnospiraceae_NK4A136 group, and Ruminococcus genus.

Synthesis and anti-proliferation activity of mogrol derivatives bearing quinoline and triazole moieties.

A series of novel derivatives based on mogrol were designed and synthesized in attempt to improve anti-lung cancer activity. The cytotoxicity against human lung cancer cells including A549 and NCI-H460 were performed by Cell Counting Kit-8 (CCK8) assay in vitro. The screening result showed that compound 8f exhibited the strongest activity with an IC50 value of 4.47 µM against A549 cell, and could induce the cell apoptosis in a dose-dependent manner and arrest cell cycle at G0/G1 phase. Besides, compound 8f displayed anti-proliferation effect on A549 cell through inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3). Furthermore, compared with morgol, compound 10a significantly improved the cytotoxicity against NCI-H460 with the IC50 value of 17.13 µM. The research stimulated the development of potential therapeutic agent for lung cancer from the natural mogrol.

Prolamin-based complexes: Structure design and food-related applications.

Prolamins are a group of safe food additives that are biocompatible, biodegradable, and sustainable. Zein, gliadin, kafirin, and hordein are common prolamins that have been extensively studied, particularly as these form colloidal particles because of their amphiphilic properties. Prolamin-based binary/ternary complexes, which have stable physicochemical properties and superior functionality, are formed by combining prolamins with polysaccharides, polyphenols, water-soluble proteins, and surfactants. Although the combination of prolamins with other components has received attention, the relationship between the structural design of prolamin-based complexes and their functionalities remains uncertain. This review discusses the production methods of prolamin-based complexes, the factors influencing their structural characteristics, and their applications in the food industry. Further studies are needed to elucidate the structure-function relationships between prolamins and other biopolymers, as well as the toxicological effects of these complexes in food.

Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy.

BACKGROUND AND PURPOSE: Inflammation has been considered a precipitating event that contributes to neurocognitive dysfunction in minimal hepatic encephalopathy (MHE). Inhibition TLR-4 related inflammation can effectively improve neurocognitive dysfunction of MHE. Our previous study showed that Babao Dan (BBD) effectively inhibited inflammation and ameliorated neurocognitive function in rats with acute hepatic encephalopathy (HE) and chronic HE. The mechanism may lie in the regulation of TLR4 signaling pathway. Therefore, this study aimed to evaluate the role of BBD in the treatment of MHE patients with cirrhosis and to elucidate the underlying mechanism by which BBD regulated TLR4 pathway to alleviate inflammation. METHODS: A randomized controlled trial (n = 62) was conducted to evaluate the clinical efficacy between BBD plus lactulose (n = 31) and lactulose alone (n = 31) in MHE patients by testing neurocognitive function (NCT-A and DST), blood ammonia, liver function (ALT, AST and TBIL) and blood inflammation (IL-1ß, IL-6 and TNF-α). Afterward, we detected NO, inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and the phosphorylation of P65, JNK, ERK as well as P38 in LPS-activated rat primary bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs), and mouse primary BMDMs/PMs/microglia/astrocytes, to investigate the underlying mechanism of BBD inhibiting inflammation through TLR4 pathway. Also, the survival rate of mice, liver function (ALT, AST), blood inflammation (IL-1ß, IL-6 and TNF-α), inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and histopathological changes in the liver, brain and lung were measured to assess the anti-inflammatory effect of BBD on neurocognitive function in endotoxin shock/endotoxemia mice. RESULTS: BBD combined with lactulose significantly ameliorated neurocognitive function by decreasing NCT-A (p＜0.001) and increasing DST (p＜0.001); inhibited systemic inflammation by decreasing IL-1ß (p＜0.001), IL-6(p＜0.001) and TNF-α (p＜0.001); reduced ammonia level (p = 0.005), and improved liver function by decreasing ALT(p = 0.043), AST(p = 0.003) and TBIL (p = 0.026) in MHE patients. Furthermore, BBD inhibited gene and protein expression of IL-1ß, IL-6 and TNF-α as well as NO in rat primary BMDMs/PMs, and mouse primary BMDMs/PMs/microglia/astrocytes in a dose-dependent manner. BBD inhibited the activation of mouse primary BMDMs/PMs/microglia/astrocytes by regulating TLR4 pathway involving the phosphorylation of P65, JNK, ERK and P38. Also, BBD reduced the mortality of mice with endotoxin shock/endotoxemia; serum levels of ALT, AST, IL-1ß, IL-6 and TNF-α; gene expression of IL-1ß, IL-6 and TNF-α in the liver, brain and lung, and tissue damage in the liver and lung. CONCLUSION: Our study provided for the first time clinical and experimental evidence supporting the use of BBD in MHE, and revealed that BBD could play a crucial role in targeting and regulating TLR4 inflammatory pathway to improve neurocognitive function in MHE patients.

Fabrication of Composite Structures of Lysozyme Fibril-Zein using Antisolvent Precipitation: Effects of Blending and pH Adjustment Sequences.

Antisolvent precipitation is a widely used method to fabricate prolamin-based composites. In the present study, composite structures of lysozyme amyloid fibrils with zein proteins were fabricated using the antisolvent precipitation method by applying different blending and pH adjustment sequences. Globular prolamins were bound to the amyloid fibrils to combine their respective advantages. The dynamic light scattering showed that the composites with a characteristic stabilized behavior (43.60 ± 1.75 mV ∼ 35.20 ± 0.65 mV) were formed at pH 4.0-5.0, in which noncovalent interactions between fibril and particles occurred. Two different structures: fruit tree-like structure and beaded-like structure, were presented in AFM and TEM images due to the different pH adjustment sequences, while blending sequences had negligible effect on the morphology of the composites. A fruit tree-like entity was detected for lysozyme fibril-zein composites, where its "branches" bear zein globular particles. A beaded-like structure was observed for lysozyme fibril-zein composites, where lysozyme fibril was the thread and zein aggregates were the beads. The potential mechanism of this phenomenon can be explained as the fruit tree-like structure being primarily formed through electrostatic interactions while the beaded-like structure is mainly caused by hydrophobic interactions. The composites of fruit tree-like structures hold a more promising stability than those with beaded-like structures. The results of this research would give constructive information for the fabrication of amyloid fibril-prolamin protein composites, which may exhibit the combined advantages of each components and have potential applications in encapsulation and protection of bioactive substances and stabilizing emulsions.

Fabrication, Characterization, and Formation Mechanism of Zein-Gum Arabic Nanocomposites in Aqueous Ethanol Solution with a High Ethanol Content.

The antisolvent precipitation method is widely applied to produce zein colloidal particles. The process involves dissolving zein in 55-90% (v/v) alcohol/water mixtures and then shearing such solutions into deionized water to lower the ethanol content. In the present work, on the basis of the preliminary result that gum arabic (GA) was able to well disperse in 70% (v/v) alcohol/water mixtures, a new way was created to produce zein-GA nanocomposites by simply mixing their aqueous alcohol solution with a high alcohol level of 70% (v/v) at pH 8.0. Findings showed that the multimodal size distribution of zein or GA alone was shifted to be the monomodal peak after zein and GA aqueous ethanol solution was mixed, indicating the successful formation of zein-GA nanocomposites. A core-shell structure was observed for zein-GA nanocomposites, with zein as a core and GA as a shell. In addition, the incorporation of GA caused the conformational and second structural changes of zein. A two-step mechanism was involved to explain the formation of zein-GA nanocomposites. The first step was that GA addition changed the polarity of zein aqueous ethanol solution and zein nanoparticles formed, and the second step was that hydrogen bonds and hydrophobic interactions promoted the adsorption of GA onto the particle surfaces. Results in this work would provide a new sight into the design of zein-based nanocomplexes, which may have potential applications, such as constructing delivery systems, for bioactive compounds.

Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities.

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 µM, 1.87 µM, and 1.19 µM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 µM and 1.37 µM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 µM.