Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet-Induced Non-Alcoholic Steatohepatitis (NASH) Mice.

SCOPE: Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A1 and SS-Bb) against NASH and explores the mechanisms by targeting GM. METHODS AND RESULTS: Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A1 , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A1 , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A1 and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A1 and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A1 and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A1 and SS-Bb against NASH. CONCLUSION: GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice.

A dual-subcellular localized ß-glucosidase confers pathogen and insect resistance without a yield penalty in maize.

Maize is one of the most important crops for food, cattle feed and energy production. However, maize is frequently attacked by various pathogens and pests, which pose a significant threat to maize yield and quality. Identification of quantitative trait loci and genes for resistance to pests will provide the basis for resistance breeding in maize. Here, a ß-glucosidase ZmBGLU17 was identified as a resistance gene against Pythium aphanidermatum, one of the causal agents of corn stalk rot, by genome-wide association analysis. Genetic analysis showed that both structural variations at the promoter and a single nucleotide polymorphism at the fifth intron distinguish the two ZmBGLU17 alleles. The causative polymorphism near the GT-AG splice site activates cryptic alternative splicing and intron retention of ZmBGLU17 mRNA, leading to the downregulation of functional ZmBGLU17 transcripts. ZmBGLU17 localizes in both the extracellular matrix and vacuole and contribute to the accumulation of two defence metabolites lignin and DIMBOA. Silencing of ZmBGLU17 reduces maize resistance against P. aphanidermatum, while overexpression significantly enhances resistance of maize against both the oomycete pathogen P. aphanidermatum and the Asian corn borer Ostrinia furnacalis. Notably, ZmBGLU17 overexpression lines exhibited normal growth and yield phenotype in the field. Taken together, our findings reveal that the apoplastic and vacuolar localized ZmBGLU17 confers resistance to both pathogens and insect pests in maize without a yield penalty, by fine-tuning the accumulation of lignin and DIMBOA.

The plant immune receptor SNC1 monitors helper NLRs targeted by a bacterial effector.

Plants deploy intracellular receptors to counteract pathogen effectors that suppress cell-surface-receptor-mediated immunity. To what extent pathogens manipulate intracellular receptor-mediated immunity, and how plants tackle such manipulation, remains unknown. Arabidopsis thaliana encodes three similar ADR1 class helper nucleotide-binding domain leucine-rich repeat receptors (ADR1, ADR1-L1, and ADR1-L2), which are crucial in plant immunity initiated by intracellular receptors. Here, we report that Pseudomonas syringae effector AvrPtoB suppresses ADR1-L1- and ADR1-L2-mediated cell death. ADR1, however, evades such suppression by diversifying into two ubiquitination sites targeted by AvrPtoB. The intracellular sensor SNC1 interacts with and guards the CCR domains of ADR1-L1/L2. Removal of ADR1-L1/L2 or delivery of AvrPtoB activates SNC1, which then signals through ADR1 to trigger immunity. Our work elucidates the long-sought-after function of SNC1 in defense, and also how plants can use dual strategies, sequence diversification, and a multi-layered guard-guardee system, to counteract pathogen's attack on core immunity functions.

Small proteins modulate ion-channel-like ACD6 to regulate immunity in Arabidopsis thaliana.

The multi-pass transmembrane protein ACCELERATED CELL DEATH 6 (ACD6) is an immune regulator in Arabidopsis thaliana with an unclear biochemical mode of action. We have identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for ∼7 kDa proteins, which differentially interact with specific ACD6 variants. MHA1L enhances the accumulation of an ACD6 complex, thereby increasing the activity of the ACD6 standard allele for regulating plant growth and defenses. The intracellular ankyrin repeats of ACD6 are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, with MHA1L as a direct regulator of ACD6, indicating that peptide-regulated ion channels are not restricted to animals.

Predictors of failure of early neurological improvement in early time window following endovascular thrombectomy: a multi-center study.

Background and objective: Endovascular thrombectomy (EVT) has become the gold standard in the treatment of acute stroke patients. However, not all patients respond well to this treatment despite successful attempts. In this study, we aimed to identify variables associated with the failure of improvements following EVT. Methods: We retrospectively analyzed prospectively collected data of 292 ischemic stroke patients with large vessel occlusion who underwent EVT at three academic stroke centers in China from January 2019 to February 2022. All patients were above 18 years old and had symptoms onset ≤6 h. A decrease of more than 4 points on the National Institute of Health Stroke Scale (NIHSS) after 24 h compared with admission or an NIHSS of 0 or 1 after 24 h was defined as early neurological improvement (ENI), whereas a lack of such improvement in the NIHSS was defined as a failure of early neurological improvement (FENI). A favorable outcome was defined as a modified Rankin scale (mRS) score of 0-2 after 90 days. Results: A total of 183 patients were included in the final analyses, 126 of whom had FENI, while 57 had ENI. Favorable outcomes occurred in 80.7% of patients in the ENI group, in contrast to only 22.2% in the FENI group (p < 0.001). Mortality was 7.0% in the ENI group in comparison to 42.1% in the FENI group (p < 0.001). The multiple logistic regression model showed that diabetes mellitus [OR (95% CI), 2.985 (1.070-8.324), p = 0.037], pre-stroke mRS [OR (95% CI), 6.221 (1.421-27.248), p = 0.015], last known well to puncture time [OR (95% CI), 1.010 (1.003-1.016), p = 0.002], modified thrombolysis in cerebral infarction = 3 [OR (95% CI), 0.291 (0.122-0.692), p = 0.005], and number of mechanical thrombectomy passes [OR (95% CI), 1.582 (1.087-2.302), p = 0.017] were the predictors of FENI. Conclusion: Diabetes mellitus history, pre-stroke mRS, longer last known well-to-puncture time, lack of modified thrombolysis in cerebral infarction = 3, and the number of mechanical thrombectomy passes are the predictors of FENI. Future large-scale studies are required to validate these findings.

Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy.

T cells play a basic and key role in immunotherapy against solid tumors, and efficiently recruiting them into neoplastic foci and sustaining long-term effector function are consistent goals that remain a critical challenge. Here, an injectable alginate-based hydrogel with abundant ß-cyclodextrin (ALG-ßCD) sites is developed and intratumorally injected to recruit CCR9+ CD8+ T cells (a subset of T cells with robust antitumor activity) via the trapped chemokine CCL25. In the meantime, an intravenously injected adamantane-decorated anti-PD1 antibody (Ad-aPD1) would hitchhike on recruited CCR9+ CD8+ T cells to achieve the improved intratumoral accumulation of Ad-aPD1. Moreover, the Ad-PD1 and Ad-PDL1 antibodies are immobilized in the ALG-ßCD hydrogel through supramolecular host-guest interactions of Ad and ßCD, which facilitate engagement between CD8+ T cells and tumor cells and reinvigorate CD8+ T cells to avoid exhaustion. Based on this treatment strategy, T cell-mediated anticancer activity is promoted at multiple levels, eventually achieving superior antitumor efficacy in both orthotopic and postsurgical B16-F10 tumor models.

Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation.

SCOPE: Exosomes, a novel type of bioactive component in human milk (HM), affect infant development, growth, and health. Recent studies indicate that HM exosomes and miRNAs relate to gestational diabetes mellitus (GDM). However, the miRNAs profiles and functionalities of HM exosomes from GDM parturient remain unclear. This study aims to compare the differential miRNAs in HM exosomes from GDM and healthy parturient, and investigate the HM exosomes bioactivities in regulating hepatocyte proliferation and insulin sensitivity. METHODS AND RESULTS: This study extracted HM exosomes from GDM (GDM-EXO) and healthy (NOR-EXO) parturient by ultracentrifugation, high-throughput sequenced and compared the exosomal miRNAs profiles, and explored the regulatory bioactivities on hepatocyte proliferation in HepG2 cells and Balb/c mice. As compared to NOR-EXO, GDM-EXO has similar morphology, size, concentration, and exosome-specific markers (CD9 and TSG101) expression. GDM-EXO and NOR-EXO specifically harbor 1299 and 8 miRNAs, respectively. Moreover, GDM-EXO had 176 upregulated and 47 downregulated miRNAs compared with NOR-EXO. Both GDM-EXO and NOR-EXO were absorbed in cultured HepG2 hepatocytes and mice liver. GDM-EXO inhibited hepatocytes proliferation by downregulating mammalian target of rapamycin (mTOR) possibly via exosomal miR-101-3p delivery. CONCLUSION: HM exosomes from GDM and healthy parturient exhibit differential miRNAs profiles and distinct regulatory bioactivity on hepatocyte proliferation.

A manganese-phenolic network platform amplifying STING activation to potentiate MRI guided cancer chemo-/chemodynamic/immune therapy.

Low immune infiltration severely hinders the efficacy of cancer immunotherapy. Here, we developed a manganese-phenolic network platform (TMPD) to boost antitumor immunity via a stimulator of interferon gene (STING)-amplified activation cascade. TMPD is based on doxorubicin (DOX)-loaded PEG-PLGA nanoparticles and further coated with manganese (Mn2+)-tannic acid (TA) networks. Mechanistically, DOX-based chemotherapy and Mn2+-mediated chemodynamic therapy effectively promoted immunogenic cell death (ICD), characterized by abundant damage-associated molecular pattern (DAMP) exposure, which subsequently enhanced dendritic cells' (DCs) presentation of antigens. DOX-elicited DNA damage simultaneously caused cytoplasmic leakage of intracellular double-stranded DNA (dsDNA) as the STING signal initiator, while Mn2+ mediated significant upregulation in the expression of a STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of TMPD remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Meanwhile, the released Mn2+ could serve as a contrast agent for tumor-specific T1-weighted magnetic resonance imaging (MRI). Moreover, TMPD combined with immune checkpoint blockade (ICB) immunotherapy significantly inhibited tumor growth and lung metastasis. Collectively, these findings indicate that TMPD has great potential in activating robust innate and adaptive immunity for MRI guided cancer chemo-/chemodynamic/immune therapy.

Analysis of the Induced Stress Fields Around Hydraulic Fractures Considering the Influence of Natural Fractures and Bedding Planes.

Natural fractures (NFs) and bedding planes (BPs) are well developed in shale reservoirs. The propagation of hydraulic fractures (HFs) and the opening of NFs and BPs can produce induced stress fields (ISFs) within the fracturing process, causing interference to the in situ stress field. Aiming at the "stress shadow" effect among HFs in horizontal wells, the calculation models of HFs, BPs, and NFs for induced stress distributions are established based on displacement discontinuity theory, which can quantitatively characterize the composite ISF of the three under different connecting states. In addition, the interference coefficient of stress intensity factor (ICSIF) is introduced to quantitatively evaluate the interference degree of the composite ISF to the propagation of HFs. The results show that: (1) the ISF forms a "tensile stress concentration zone" near the fracture surface to promote the HFs opening and a "compressive stress concentration zone" at the fracture tips to suppress the propagation of HFs; (2) the ISF forms an elliptical effective swept area around the fracture, which is affected by the propagation height of HFs, while NFs or BPs generate local disturbances to the ISF; (3) the in situ stress reverses in the swept area, and the stress reversal interval is related to the in situ stress difference, fracture propagation height, Poisson's ratio, fracture net pressure, and fracture spacing; (4) the reasonable fracture spacing and fracture propagation height of horizontal wells can be determined by the ICSIF. The study can provide theoretical guidance for optimizing the fracture spacing and promoting the uniform propagation of multiple fractures in staged fracturing of horizontal wells.

Advances in the Bioactivities of Phytochemical Saponins in the Prevention and Treatment of Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by hardening and narrowing of arteries. AS leads to a number of arteriosclerotic vascular diseases including cardiovascular diseases, cerebrovascular disease and peripheral artery disease, which pose a big threat to human health. Phytochemicals are a variety of intermediate or terminal low molecular weight secondary metabolites produced during plant energy metabolism. Phytochemicals from plant foods (vegetables, fruits, whole grains) and traditional herb plants have been shown to exhibit multiple bioactivities which are beneficial for prevention and treatment against AS. Many types of phytochemicals including polyphenols, saponins, carotenoids, terpenoids, organic sulfur compounds, phytoestrogens, phytic acids and plant sterols have already been identified, among which saponins are a family of glycosidic compounds consisting of a hydrophobic aglycone (sapogenin) linked to hydrophilic sugar moieties. In recent years, studies have shown that saponins exhibit a number of biological activities such as anti-inflammation, anti-oxidation, cholesterol-lowering, immunomodulation, anti-platelet aggregation, etc., which are helpful in the prevention and treatment of AS. This review aims to summarize the recent advances in the anti-atherosclerotic bioactivities of saponins such as ginsenoside, soyasaponin, astra-galoside, glycyrrhizin, gypenoside, dioscin, saikosaponin, etc.

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Effects of Acupuncture on Cortical Activation in Patients with Disorders of Consciousness: A Functional Near-Infrared Spectroscopy Study.

Background: Disorder of consciousness (DoC) is a clinical condition caused by severe brain damage. Some studies have reported that acupuncture, a traditional Chinese treatment, could facilitate the recovery of the patient's consciousness. The therapeutic effects of acupuncture may be due to its modulation of facilitating cortex (PFC) activity, but it has not been greatly demonstrated. Objectives: We intended to observe the effects of acupuncture on prefrontal cortical activity, explore the potential correlation between cortical activation and the severity of DoC, and analyze the functional brain network connectivity to provide a theoretical basis for its application in clinical practice. Methods: Participants diagnosed with DoC were included in the study. Before the intervention, we assessed the patient's state of consciousness using relevant scales, such as the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R). All patients received acupuncture manipulation with the functional near-infrared spectroscopy (fNIRS) system monitored. Result: A total of 16 subjects participated in our study. We observed that the concentration of oxygenated hemoglobin (HbO) in the PFC was increased during the acupuncture manipulation and declined during the resting state. Then, the connection strength of the left cerebral cortex was generally higher than that of the right. Finally, we observed only a weak difference in hemodynamic responses of PFC between the vegetative state (VS) and minimally conscious state (MCS) groups. However, the difference was not statistically significant. Conclusion: Our results indicated that acupuncture can increase the concentration of HbO in the PFC and strengthen the connection strength of the left cerebral cortex. However, our present study did not find a significant correlation between the cortical hemodynamic response and the severity of DoC.

Inflammation Induced by Lipopolysaccharide and Palmitic Acid Increases Cholesterol Accumulation via Enhancing Myeloid Differentiation Factor 88 Expression in HepG2 Cells.

Recently, multiple studies have shown that chronic inflammation disturbs cholesterol homeostasis and promotes its accumulation in the liver. The underlying molecular mechanism remains to be revealed. The relationship between the toll-like receptor 4 (TLR4) inflammatory signaling pathway and cholesterol accumulation was investigated in HepG2 cells treated with lipopolysaccharide (LPS) or palmitic acid (PA) for different lengths of time. In addition, the effects of pretreatment with 20µmol/L ST2825 (MyD88 inhibitor) were also studied in LPS- or PA-treated HepG2 cells and myeloid differentiation factor 88 (MyD88)-overexpressing HEK293T cells. The intracellular total and free cholesterol levels were measured using a commercial kit and filipin staining, respectively. The expression levels of sterol regulatory element-binding protein-2 (SREBP-2) and components in the TLR4 signaling pathway were determined using Western blotting. The treatments with LPS for 12 h and with PA for 24 h significantly increased the contents of intracellular total and free cholesterol, as well as the expression levels of SREBP-2 and components in the TLR4 signaling pathway. The inhibition of MyD88 by ST2825 significantly decreased the cholesterol content and the expression levels of SREBP-2 and components of the TLR4/MyD88/NF-κB pathway in HepG2 cells, as well as MyD88-overexpressing HEK293T cells. These results indicated that LPS and PA treatments increase SREBP-2-mediated cholesterol accumulation via the activation of the TLR4/MyD88/NF-κB signaling pathway in HepG2 cells.

The Extraction of ß-Carotene from Microalgae for Testing Their Health Benefits.

ß-carotene, a member of the carotenoid family, is a provitamin A, and can be converted into vitamin A (retinol), which plays essential roles in the regulation of physiological functions in animal bodies. Microalgae synthesize a variety of carotenoids including ß-carotene and are a rich source of natural ß-carotene. This has attracted the attention of researchers in academia and the biotech industry. Methods to enrich or purify ß-carotene from microalgae have been investigated, and experiments to understand the biological functions of microalgae products containing ß-carotene have been conducted. To better understand the use of microalgae to produce ß-carotene and other carotenoids, we have searched PubMed in August 2021 for the recent studies that are focused on microalgae carotenoid content, the extraction methods to produce ß-carotene from microalgae, and the bioactivities of ß-carotene from microalgae. Articles published in peer-reviewed scientific journals were identified, screened, and summarized here. So far, various types and amounts of carotenoids have been identified and extracted in different types of microalgae. Diverse methods have been developed overtime to extract ß-carotene efficiently and practically from microalgae for mass production. It appears that methods have been developed to simplify the steps and extract ß-carotene directly and efficiently. Multiple studies have shown that extracts or whole organism of microalgae containing ß-carotene have activities to promote lifespan in lab animals and reduce oxidative stress in culture cells, etc. Nevertheless, more studies are warranted to study the health benefits and functional mechanisms of ß-carotene in these microalgae extracts, which may benefit human and animal health in the future.

An LRR-only protein promotes NLP-triggered cell death and disease susceptibility by facilitating oligomerization of NLP in Arabidopsis.

Necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) constitute a superfamily of proteins toxic to dicot plants, but the molecular basis of this toxicity remains obscure. Using quantitative trait locus (QTL) analysis we investigated the genetic variation underlying ion leakage in Arabidopsis plants elicited with MoNLP1 derived from Magnaporthe oryzae. The QTL conditioning MoNLP1 toxicity was positionally cloned and further characterized to elucidate its mode of action. MoNLP1-triggered cell death varied significantly across > 250 Arabidopsis accessions and three QTLs were identified conferring the observed variation. The QTL on chromosome 4 was uncovered to encode a leucine-rich repeat (LRR)-only protein designated as NTCD4, which shares high sequence identity with a set of nucleotide-binding LRR proteins. NTCD4 was secreted into the apoplast and physically interacted with multiple NLPs. Apoplastic NTCD4 facilitated the oligomerization of NLP, which was closely associated with toxicity in planta. The natural genetic variation causing D3N change in NTCD4 reduced the secretion efficiency of NTCD4 and the infection of Botrytis cinerea on Arabidopsis plants. These observations demonstrate that the plant-derived NTCD4 is recruited by NLPs to promote toxicity via facilitating their oligomerization, which extends our understanding of a key step in the toxic mode of action of NLPs.

Soyasaponin A2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline-Deficient (MCD) Diet-induced Nonalcoholic Steatohepatitis (NASH) Mice.

SCOPE: Nonalcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health-promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS-A2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota. METHODS AND RESULTS: The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A2 for 16 weeks. Hepatic pathology is assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A2 significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA. CONCLUSION: SS-A2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.

Soyasaponins reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts.

BACKGROUND: Previous studies indicate that soyasaponins may reduce inflammation via modulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling. However, its underlying mechanisms are still not fully understood. METHODS: Lipopolysaccharide (LPS)-challenged inflamed male ICR mice were intervened by intragastrical administration with 10 and 20 µmol/kg·BW of soyasaponin A1, A2 or I for 8 weeks. The serum inflammatory markers were determined by commercial kits and the expression of molecules in TLR4/MyD88 signaling pathway in liver by real-time PCR and western blotting. The recruitments of TLR4 and MyD88 into lipid rafts of live tissue lysates were detected by sucrose gradient ultracentrifugation and western blotting. LPS-stimulated RAW264.7 macrophages were treated with 10, 20 and 40 µmol/L of soyasaponin A1, A2 or I for 2 h. MyD88-overexpressed HEK293T cells were treated with 20 and 40 µmol/L of soyasaponins (A1, A2 or I) or 20 µmol/L of ST2825 (a MyD88 inhibitor) for 6 h. The expression of molecules in TLR4/MyD88 signaling pathway were determined by western blotting. Data were analyzed by using one way analysis of variance or t-test by SPSS 20.0 statistical software. RESULTS: Soyasaponins A1, A2 or I significantly reduced the levels of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and nitric oxide (NO) in serum (p < 0.05), and decreased the mRNA levels of TNFα, IL-6, IL-1ß, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (p < 0.05), the protein levels of myeloid differentiation protein 2 (MD-2), TLR4, MyD88, toll-interleukin1 receptor domain containing adaptor protein (TIRAP), phosphorylated interleukin-1 receptor-associated kinase 4 (p-IRAK-4), phosphorylated interleukin-1 receptor-associated kinase 1 (p-IRAK-1) and TNF receptor associated factor 6 (TRAF6) (p < 0.05), and the recruitments of TLR4 and MyD88 into lipid rafts in liver (p < 0.05). In LPS-stimulated macrophages, soyasaponins A2 or I significantly decreased MyD88 (p < 0.05), soyasaponins A1, A2 or I reduced p-IRAK-4 and p-IRAK-1 (p < 0.05), and soyasaponin I decreased TRAF6 (p < 0.05). In MyD88-overexpressed HEK293T cells, soyasaponins (A1, A2 or I) and ST2825 significantly decreased MyD88 and TRAF6 (p < 0.05). CONCLUSION: Soyasaponins can reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts. This study provides novel understanding about the anti-inflammatory mechanism of soyasaponins.

Soyasaponins A1 and A2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in high fat diet (HFD)-fed ApoE-/- mice.

Atherosclerosis is a chronic inflammatory disease causing coronary heart attacks and strokes. Soyasaponins (SS), the phytochemicals naturally existing in soybeans and their products, have been shown to reduce hypercholesterolemia and inflammation, which are intimately related to the genesis and development of atherosclerosis. However, the anti-atherosclerotic functionality of soyasaponins remains unknown. The aim of this study was to investigate the effects of the supplementation of two types of soyasaponin monomers (A1 and A2) on atherosclerotic plaque formation, serum lipid profiles, and inflammation in ApoE gene knockout (ApoE-/-) mice. Sixty 5-week-old ApoE-/- male mice were fed with a high-fat diet (HFD) and intervened by SSA1 and SSA2 (10 and 20 µmol per kg BW, respectively) or simvastatin (10 µmol per kg BW) for 24 weeks. The atherosclerotic lesions in the aorta, aortic root, and innominate artery, lipid profile and inflammatory markers in serum, and TLR4/MyD88/NF-κB signaling in arterial tissues were determined. SSA1 and SSA2 decreased the plaque ratio in the aortic root and innominate artery but not in the entire aorta. In serum, SSA1 reduced TG, TC, and LDL-C but increased HDL-C; SSA2 decreased TC, TG, and LDL-C but did not affect HDL-C. Meanwhile, SSA1 increased TG, SSA2 increased TC, and both of them increased bile acids in the feces. SSA1 and SSA2 lowered TNF-α, MCP-1, and hs-crp in serum. Furthermore, SSA1 and SSA2 reduced the TLR4 and MyD88 expressions in the aorta and innominate artery and inhibited NF-κB p65 and IκBα phosphorylation in the aorta. These results suggest that SSA1 and SSA2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in HFD-fed ApoE-/- mice.

Investigation on Plugging and Profile Control of Polymer Microspheres as a Displacement Fluid in Enhanced Oil Recovery.

Polymer microspheres (PMs) are used as a new material to recover residual oil left in unswept oil areas after secondary recovery methods. The fact that the PMs plug the macropores causes the flow direction of the injection fluid to be transferred from macropores to micropores. In order to investigate the plugging and profile control mechanisms of PMs in reservoirs, four kinds of PMs with different particle sizes and four kinds of artificial cores with different permeability were selected for flooding tests, including plugging experiments and profile control experiments. The pore throat size distribution of cores was characterized by nuclear magnetic resonance (NMR) technology. The particle size distribution of PMs used in the experiment was characterized using a laser particle size analyzer. The results showed that there are six matching relationships existing simultaneously between pore throats and PMs based on theoretical analysis, which are completely plugging, single plugging, bridge plugging, smooth passing, deposition, and deformable passing. A key principle for optimizing PMs in profile control is that the particle size of the selected PMs can enter the high permeability layer well, but it is difficult for it to enter the low permeability layer. The results of this paper provide a theoretical basis for the optimal particle size of PMs during the oil field profile control process.

Soyasaponins Reduce Inflammation and Improve Serum Lipid Profiles and Glucose Homeostasis in High Fat Diet-Induced Obese Mice.

SCOPE: Obesity is linked to a chronic low-grade inflammatory state that contributes to the development of obesity-associated metabolic disorders. The anti-inflammatory activities and mechanisms of soyasaponin monomers (A1 , A2 , and I) have been recently demonstrated in cell models. However, their potential in vivo abilities to reduce chronic inflammation and alleviate metabolic disorders in obese status remain unclear. METHODS AND RESULTS: High fat diet (HFD)-fed obese male C57BL/6J mice are intervened by aspirin (0.1 mg kg-1 body weight) or 20 mg kg-1 of soyasaponins A1 , A2 , or I for 8 weeks. Soyasaponins A1 , A2 , and I significantly reduce pro-inflammatory cytokines/mediators in serum, liver, and white adipose tissues (WATs), improve serum lipid profiles, decrease liver cholesterol, triglyceride and steatosis, and promote fecal excretion of cholesterol, triglycerides, and bile acids. Soyasaponins A1 , A2 , and I also decrease IKKα/ß phosphorylation in liver and WATs and reduce NF-κB p65 phosphorylation and CD68 mRNA and protein expression in WATs. Soyasaponins A1 and A2 but not I decrease NF-κB p65 phosphorylation in liver and adipocytes hypertrophy in WATs. In addition, Soyasaponin A2 but not A1 nor I decreases fasting blood glucose and improved insulin resistance. CONCLUSION: Soyasaponins reduce inflammation and improve serum lipid profiles and glucose homeostasis in HFD-induced obese mice.