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Background: Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. Methods: Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. Results: Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1β and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. Conclusion: Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats. [ABSTRACT FROM AUTHOR]

GRP75 (75-kDA glucose-regulated protein), defined as a major component of both the mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both in vitro and in vivo models with insulin resistance. We found that GRP75 was downregulated in mice fed a high-fat diet (HFD) and that induction of Grp75 in mice could prevent HFD-induced obesity and insulin resistance. Mechanistically, GRP75 influenced insulin sensitivity by regulating mitochondrial function through its modulation of mitochondrial-supercomplex turnover rather than mitochondria-associated membrane communication: GRP75 was negatively associated with respiratory chain complex activity and was essential for mitochondrial-supercomplex assembly and stabilization. Moreover, mitochondrial dysfunction in Grp75-knockdown cells might further increase mitochondrial fragmentation, thus triggering cytosolic mtDNA release and activating the cGAS/STING-dependent proinflammatory response. Therefore, GRP75 can serve as a potential therapeutic target of insulin resistant-related diabetes or other metabolic diseases. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Qiang Zhang, Ting Luo and Dezheng Yuan. Reference 1 Zhang, Q, Luo, T, Yuan, D, Fu, Y, Yuan J. Mechanism study of Qilongtian on pulmonary fibrosis in bleomycin model mice. [Extracted from the article]

• New water-soluble Aβ probes based on AIE mechanism were developed. • The probes showed more remarkable affinity to Aβ aggregates than commercial ThT. • The probes possessed rapid staining and washing-free imaging to Aβ plaques. • An efficient approach for mapping of Aβ plaques in whole brain was developed. Rapid verification and three-dimensional (3D) mapping of β-amyloid (Aβ) plaques in mouse whole brain is of great significance in early diagnosis of Alzheimer's disease (AD) due to the intricate relationship of Aβ plaques with their surrounding microenvironment. Previously reported fluorescent labelling to locate Aβ plaques usually require lengthy permeation/staining/washing procedures to eliminate non-specific binding and improve fluorescence signal-to-noise ratio, which is inaccessible to automatic brain wide 3D imaging. Here we report a kind of water-soluble fluorescent probes with aggregation-induced emission (AIE) activities, named AIEgens, which can rapidly permeate and stain Aβ plaques of transgenic (Tg) mouse brain sections into 8 μm of depth within 1 min. The excellent water-solubility, specificity and sensitivity of AIEgens for Aβ plaques enable rapid staining and washing-free imaging of brain sections. The automatic 3D mapping of Aβ plaques in Tg mouse's whole brain is implemented through the cycling process of in situ real-time mechanical sectioning, staining and imaging with AIEgens in fluorescent micro-optical sectioning tomography (fMOST) system. The AIE-based fMOST, which integrates the in-situ staining/imaging/sectioning steps of Tg mouse's whole brain, provides an automatic 3D mapping solution to access the size, morphology and 3D distribution of Aβ plaques in mouse whole brain, which would help to explore the correlation between Aβ structure and neurodegenerative activity. [ABSTRACT FROM AUTHOR]

• New water-soluble Aβ probes based on AIE mechanism were developed. • The probes showed more remarkable affinity to Aβ aggregates than commercial ThT. • The probes possessed rapid staining and washing-free imaging to Aβ plaques. • An efficient approach for mapping of Aβ plaques in whole brain was developed. Rapid verification and three-dimensional (3D) mapping of β-amyloid (Aβ) plaques in mouse whole brain is of great significance in early diagnosis of Alzheimer's disease (AD) due to the intricate relationship of Aβ plaques with their surrounding microenvironment. Previously reported fluorescent labelling to locate Aβ plaques usually require lengthy permeation/staining/washing procedures to eliminate non-specific binding and improve fluorescence signal-to-noise ratio, which is inaccessible to automatic brain wide 3D imaging. Here we report a kind of water-soluble fluorescent probes with aggregation-induced emission (AIE) activities, named AIEgens, which can rapidly permeate and stain Aβ plaques of transgenic (Tg) mouse brain sections into 8 μm of depth within 1 min. The excellent water-solubility, specificity and sensitivity of AIEgens for Aβ plaques enable rapid staining and washing-free imaging of brain sections. The automatic 3D mapping of Aβ plaques in Tg mouse's whole brain is implemented through the cycling process of in situ real-time mechanical sectioning, staining and imaging with AIEgens in fluorescent micro-optical sectioning tomography (fMOST) system. The AIE-based fMOST, which integrates the in-situ staining/imaging/sectioning steps of Tg mouse's whole brain, provides an automatic 3D mapping solution to access the size, morphology and 3D distribution of Aβ plaques in mouse whole brain, which would help to explore the correlation between Aβ structure and neurodegenerative activity. [ABSTRACT FROM AUTHOR]

Background Wine aged in oak barrels will incorporate polyphenols inherent in the staves, suggesting that wine stored in these wooden containers will introduce oak compounds into the human body after consumption. Objective The purpose of the present study is to test whether consumption of these oak compounds could favorably influence metabolism in mice fed an obesogenic diet. Methods C57BL/6  male mice (n  = 8) were fed diets for 10 wk as follows: low-fat (LF), high-fat (HF), and HF containing 0.17% of oak tannin (HF+OT). A second 10-wk study was completed; mice were provided LF, HF, and HF diets supplemented with 7.0% of concentrates made from oaked wine (HF+OWC) or unoaked wine (HF+UWC). Physiological parameters were measured during the feeding trial and serum markers and hepatic gene expression measured from samples obtained at necropsy. Results Intake of HF+OT significantly reduced body-weight gain (18.4 ± 1.2 g in HF vs. 13.2 ± 1.4 g in HF+OT, P  < 0.05). Serum resistin concentrations were lower in HF+OT mice compared with HF mice (301 ± 10.1 pg/mL in HF+OT vs. 374 ± 10.9 pg/mL in HF; P  < 0.05). Hepatic lipid accumulation and expression of glutathione- S -transferase-m2 (Gstm2) and NAD(P)H:quinone oxidoreductase (Nqo1) mRNAs were significantly decreased in HF+OT compared with HF mice (P  < 0.05). When compared with HF-fed mice, intake of both OWC and UWC decreased body-weight gain (P  < 0.05), with no significant impact on food consumption. Fasting glucose concentrations, serum insulin, and hepatic lipid accumulation were reduced in HF+OWC-fed mice compared with HF+UWC-fed mice (P  < 0.05). Furthermore, hepatic glutathione- S -transferase-a1 (Gsta1) mRNA levels were significantly reduced in OWC-supplemented (0.25 ± 0.08) compared with UWC-supplemented (1.71 ± 0.24) mice (P  < 0.05). Conclusions In this mouse model of metabolic disease, intake of OTs and a concentrate made from an oaked wine had a potent impact on alleviating HF-induced metabolic syndrome. Thus, intake of OTs, provided passively in oaked wine or as a dietary supplement, may act as an agent to attenuate the markers of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Microplastic (MP) has become a concerning global environmental problem. It is toxic to aquatic organisms and can spread through the food chain to ultimately pose a threat to humans. In the environment, MP can interact with microbes and act as a microbial habitat. However, effects of polystyrene MP on the gut microbiota in mammals remain unclear. Here, male mice were exposed to two different sizes of polystyrene MP for 5 weeks to explore its effect. We observed that oral exposure to 1000 μg/L of 0.5 and 50 μm polystyrene MP decreased the body, liver and lipid weights in mice. Mucus secretion in the gut decreased in both sizes of polystyrene MP-treated groups. Regarding the gut microbiota, at the phylum level, polystyrene MP exposure decreased the relative abundances of Firmicutes and α- Proteobacteria in the feces. Furthermore, high throughput sequencing of the V3-V4 region of the 16S rRNA gene revealed significant changes in the richness and diversity of the gut microbiota in the cecums of polystyrene MP-treated mice. At the genus level, a total of 6 and 8 types of bacteria changed in the 0.5 and 50 μm polystyrene MP-treated groups, respectively. Furthermore, an operational taxonomic unit (OTU) analysis identified that 310 and 160 gut microbes were changed in the 0.5 and 50 μm polystyrene MP-treated groups, respectively. In addition, the hepatic triglyceride (TG) and total cholesterol (TCH) levels decreased in both 1000 μg/L 0.5 and 50 μm polystyrene MP-treated groups. Correspondingly, the relative mRNA levels of some key genes related to lipogenesis and TG synthesis decreased in the liver and epididymal fat. These results indicated that polystyrene MP could modify the gut microbiota composition and induce hepatic lipid disorder in mice; while the mouse is a common mammal model, consequently, the health risks of MP to animals should not be ignored. [ABSTRACT FROM AUTHOR]

Various circular RNAs (circRNAs) are novel class of non-coding RNAs, which are pervasively transcribed in the genome. CircRNAs play important roles in human, animals and plants. Up to now, there was no report regarding circRNAs of cleft palate by 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) induce. The present study screened identification and characterization of differential expressed-circRNAs in TCDD-induced cleft palate. 6903 circRNAs candidates came from cleft palates. Among them, 3525 circRNAs are up-regulation, and 3378 circRNAs are down-regulation by TCDD induce. The cluster and GO analysis found that circRNAs involved in biological process, cellular component, and molecular function. Through the analysis of KEGG Pathway, circRNAs made functions via classical signaling pathway in cleft palate, such as TGF-beta signaling pathway, BMP signal pathway, MAPK signaling pathway. In addition, we found down-regulated circRNA224, circRNA3302 and up-regulated circRNA5021 targeted tgfbr3, but up-regulated circRNA4451 targeted tgfbr2. circRNA4451 may make functions through TGF-beta signaling pathway. These results suggested that many different circRNAs may make important role in TCDD-induced cleft palate, which provided a theoretical basis for further research. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum (Leyss.Fr.) Karst is one of the well-known medicinal macrofungi all over the world, and mounting researches have focused on the polysaccharides derived from the spores of G. lucidum. In the present study, BALB/c mice (n = 8–10) were administered with crude polysaccharides of G. lucidum spores (CPGS) and the refined polysaccharides of G. lucidum spores (RPGS) for 30 days to investigate their effect on the adaptive immune system. Results showed that CPGS and RPGS displayed diverse effects on the lymphocyte activity in the spleen. The splenocyte proliferation activity upon mitogen was suppressed by CPGS and RPGS, while the NK cell's tumor-killing ability was promoted by CPGS. Both CPGS and RPGS could increase the proportion of naïve T cells in thymus, but only RPGS significantly uplifted the percentage of T cells, as well as the T cell subsets, in peripheral blood, and promoted the activation by upregulating the expression of costimulatory factor CD28. Moreover, 16S sequencing results showed that the effects of CPGS and RPGS were closely related to the regulation of gut microbiota. β-diversity of the microbiome was evidently changed by CPGS and RPGS. The phytoestrogen/polysaccharide-metabolizing bacteria (Adlercreutzia, Parabacteroides, and Prevotella), and an unclassified Desulfovibrionaceae, were remarkably enriched by CPGS or RPGS, and functions involving carbohydrate metabolism, membrane transport, and lipid metabolism were regulated. Moreover, the enrichments of Adlercreutzia, Prevotella, and Desulfovibrionaceae were positively related to the immune regulation by CPGS and RPGS, while that of Parabacteroides displayed a negative correlation. These findings suggested a promising effect of the polysaccharide from sporoderm-broken spore of G. lucidum in immune regulation to promote health control. [ABSTRACT FROM AUTHOR]

Abstract Microplastics (MPs), which are new environmental pollutants with a diameter of <5 mm, have received wide attention in recent years. However, there are still very limited data regarding the risks of MPs to animals, especially higher mammals. In this study, we exposed male mice to 5 μm pristine and fluorescent polystyrene MP for six weeks. The results showed that the polystyrene MP was observed in the guts of mice and could reduce the intestinal mucus secretion and cause damage the intestinal barrier function. In addition, high-throughput sequencing of the V3-V4 region of the 16S rRNA gene was used to explore the change of the gut microbiota composition in the cecal content. At the phylum level, the content of Actinobacteria decreased significantly in the polystyrene MP-treated group. The PD whole-tree indexes of the alpha diversity and principal component analysis (PCA) of the beta diversity indicated that the diversity of gut microbiota was altered after polystyrene MP exposure. At the genus level, a total of 15 types of bacteria changed significantly after exposure to polystyrene MP. Furthermore, the predicted KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway differences indicated that the main metabolic pathways of the functional genes in the microbial community were significantly influenced by the polystyrene MP. In addition, indexes of amino acid metabolism and bile acid metabolism in the serum were analyzed after polystyrene MP exposure. These results indicated that polystyrene MP caused metabolic disorders. In conclusion, the polystyrene MP induced gut microbiota dysbiosis, intestinal barrier dysfunction and metabolic disorders in mice. This study provided more data on the toxicity of MPs in a terrestrial organism to aid in the assessment of the health risks of polystyrene MP to animals. Graphical abstract Unlabelled Image Highlights • 5 μm polystyrene microplastic could be accumulated in the gut of mice. • 5 μm polystyrene microplastic induced intestinal barrier dysfunction in mice. • 5 μm polystyrene microplastic induced gut microbiota dysbiosis in mice. • 5 μm polystyrene microplastic induced bile acids metabolism disorder in mice. [ABSTRACT FROM AUTHOR]

Carbendazim (CBZ), a systemic, broad-spectrum benzimidazole fungicide, is widely used to control fungal diseases and has been regarded as an endocrine disruptor that causes mammalian toxicity in different target organs. Here, we discovered that chronic administrations of CBZ at 0.2, 1, and 5 mg/kg body weight for 14 weeks not only changed the composition of gut microbiota but also induced significant increases in body, liver, and epididymal fat weight in mice. At the biochemical level, the serum triglyceride (TG) and glucose levels also increased after CBZ exposure. Moreover, the level of serum lipoprotein lipase (LPL), which plays an important role in fatty acid release from TG, was decreased significantly. For gut microbiota, 16S rRNA gene sequencing and real-time qPCR revealed that CBZ exposure significantly perturbed the mice gut microbiome, and gas chromatography found that the production of short-chain fatty acids were altered. Moreover, CBZ exposure increased the absorption of exogenous TG in the mice intestine and inhibited the TG consumption, eventually leading the serum triglyceride to maintain higher levels. The increase of lipid absorption in the intestine direct caused hyperlipidemia and the multi-tissue inflammatory response. In response to the rise of lipid in blood, the body maintains the balance of lipid metabolism in mice by reducing lipid synthesis in the liver and increasing lipid storage in the fat. Chronic CBZ exposure induced the gut microbiota dysbiosis and disturbed lipid metabolism, which promoted the intestinal absorption of excess triglyceride and caused multiple tissue inflammatory responses in mice. [ABSTRACT FROM AUTHOR]

In human and rodents, some individuals may remain lean even when they are challenged with high calorie intake. Here, we used C57BL/6J mice to establish animal models of high-fat diet (HFD) induced obesity sensitive (DIO) mice and obesity resistant (DIR) mice. In DIR mice, improved metabolic profile through brown adipose tissue (BAT) activation was observed, while plasma unconjugated bile acids (BAs) were decreased together with increased intestine tauro-conjugated BAs (e.g., T-β-MCA). The composition of the gut flora also differs greatly between DIR and DOR. Using fecal microbiota transplants from DIR mice, HFD fed recipient mice exhibited a trend toward reduced adiposity and improved glucose tolerance, showing increased serum tauro-conjugated BAs levels. STC-1 cell experiments confirmed T-β-MCA could activate FXR/TGR5 pathway and induce the production of GLP-1, inhibiting genes that regulate the ceramide synthesis. Our results indicated that the DIR mice exhibited higher energy expenditure by activating BAT thermogenesis, which may be related to altered gut microbiota-bile acids-glucagon like peptide-1 axis. [ABSTRACT FROM AUTHOR]

Background: Although a reductionist approach has sought to understand the roles of individual nutrients and biochemicals in foods, it has become apparent that there can be differences when studying food components in isolation or within the natural matrix of a whole food.Objective: The objective of this study was to determine the ability of whole-food intake to modulate the development of obesity and other metabolic dysfunction in mice fed a high-fat (HF), Western-style obesogenic diet. To test the hypothesis that an n-3 (ω-3) polyunsaturated fatty acid-rich food could synergize with other, largely polyphenol-rich foods by producing greater reductions in metabolic disease conditions, the intake of English walnuts was evaluated in combination with 9 other whole foods.Methods: Eight-week-old male C57Bl/6J mice were fed low-fat (LF; 10% fat) and HF control diets, along with an HF diet with 8.6% (wt:wt) added walnuts for 9 wk. The HF control diet contained 46% fat with added sucrose (10.9%, wt:wt) and cholesterol (1%, wt:wt); the added sucrose and cholesterol were not present in the LF diet. Other groups were provided the walnut diet with a second whole food-raspberries, apples, cranberries, tart cherries, broccoli sprouts, olive oil, soy protein, or green tea. All of the energy-containing whole foods were added at an energy level equivalent to 1.5 servings/d. Body weights, food intake, and glucose tolerance were determined. Postmortem, serum lipids and inflammatory markers, hepatic fat, gene expression, and the relative concentrations of 594 biochemicals were measured.Results: The addition of walnuts with either raspberries, apples, or green tea reduced glucose area under the curve compared with the HF diet alone (-93%, -64%, and -54%, respectively, P < 0.05). Compared with HF-fed mice, mice fed walnuts with either broccoli sprouts or green tea (-49% and -61%, respectively, P < 0.05) had reduced hepatic fat concentrations. There were differences in global gene expression patterns related to whole-food content, with many examples of differences in LF- and HF-fed mice, HF- and walnut-fed mice, and mice fed walnuts and walnuts plus other foods. The mean ± SEM increase in relative hepatic concentrations of the n-3 fatty acids α-linolenic acid, eicosapentanoic acid, and docosapentanoic acid in all walnut-fed groups was 124% ± 13%, 159% ± 11%, and 114% ± 10%, respectively (P < 0.0001), compared with LF- and HF-fed mice not consuming walnuts.Conclusions: In obese male mice, walnut consumption with an HF Western-style diet caused changes in hepatic fat concentrations, gene expression patterns, and fatty acid concentrations. The addition of a second whole food in combination with walnuts produced other changes in metabolite concentrations and gene expression patterns and other physiologic markers. Importantly, these substantial changes occurred in mice fed typical amounts of intake, representing only 1.5 servings each food/d. [ABSTRACT FROM AUTHOR]

Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity. [ABSTRACT FROM AUTHOR]

Background: Intake of polyphenols and polyphenol-rich fruit extracts has been shown to reduce markers of inflammation, diabetes, and hepatic complications that result from the consumption of a high-fat (HF) diet.Objective: The objective of this study was to determine whether mice fed polyphenol-rich apple peel extract (AE), cherry extract (CE), and quercetin, a phytochemical abundant in fruits including apples and cherries, would modulate the harmful effects of adiposity on blood glucose regulation, endocrine concentrations, and hepatic metabolism in HF-fed C57BL/6J male mice.Methods: Groups of 8-wk-old mice (n = 8 each) were fed 5 diets for 10 wk, including low-fat (LF; 10% of total energy) and HF (60% of total energy) control diets and 3 HF diets containing polyphenol-rich AE, CE, and quercetin (0.2% wt:wt). Also, an in vitro study used HepG2 cells exposed to quercetin (0-100 μmol/L) to determine whether intracellular lipid accumulation could be modulated by this phytochemical.Results: Mice fed the HF control diet consumed 36% more energy, gained 14 g more body weight, and had ∼50% elevated blood glucose concentrations (all P < 0.05) than did LF-fed mice. Mice fed HF diets containing AE, CE, or quercetin became as obese as HF-fed mice, but had significantly lower blood glucose concentrations after food deprivation (-36%, -22%, -22%, respectively; P < 0.05). Concentrations of serum C-reactive protein were reduced 29% in quercetin-fed mice compared with HF-fed controls (P < 0.05). A qualitative evaluation of liver tissue sections suggested that fruit phytochemicals may reduce hepatic lipid accumulation. A quantitative analysis of lipid accumulation in HepG2 cells demonstrated a dose-dependent decrease in lipid content in cells treated with 0-100 μmol quercetin/L (P < 0.05).Conclusions: In mice, consumption of AE, CE, or quercetin appears to modulate some of the harmful effects associated with the consumption of an obesogenic HF diet. Furthermore, in a cell culture model, quercetin was shown to reduce intracellular lipid accumulation in a dose-dependent fashion. [ABSTRACT FROM AUTHOR]