內(nèi)容: Natural plant or functional food-derived biologically active ingredients have recently raised considerable interest in their antiobesity effect. However, the antiobesity role of polyphenols of white radish roots remains unknown. This study examined the therapeutic efficacy and underlying mechanisms of polyphenols extract from white radish roots (RPE) on obese mice. RPE administration significantly decreased the weight gain in high-fat diet (HFD) fed mouse models. RPE intervention also increased serum glutathione transferase and superoxide dismutase levels, and decreased malondialdehyde, tumor necrosis factor-α and lipopolysaccharide levels in the HFD-fed mice. The intervention led to an escalation in the proportion of beneficial bacteria (Akkermansia,?Clostridia), and a corresponding decline in the fraction of harmful bacteria (Proteobacteria). According to liquid chromatography-mass spectrometry-based gut metabolomics, the RPE intervention notably influenced several metabolic pathways, including those involved in protein digestion and absorption, central carbon metabolism related to cancer, and the biosynthesis of steroid hormones. Additionally, RPE treatment led to a reduction in the intestinal microbes possessing bile-salt hydrolase activity, whereas increased the expression levels of the bile acid (BA) synthesis enzyme cholesterol 7α-hydroxylase (Cyp7a1). This led to increase hepatic production and fecal excretion of BAs, reduce hepatic cholesterol, and decrease lipogenesis. Treated HDF-fed mice showed mitigation of hepatic steatosis and inflammation through gut-liver axis modulation by RPE interference. These findings together offer a significant understanding of the potential of RPE as an anti-obesity treatment and could assist in developing strategies for weight loss.

內(nèi)容: The growing aging population along with the shifting dietary paradigm to Western-type diet worldwide has been implicated in the increasing prevalence of cognitive impairment. Emerging evidence suggests that a high-fiber diet may help improve cognitive function through the gut-brain axis.?Euglena gracilis, a unicellular microalga rich in?β-1,3-glucans, has gained attention due to its modulatory effect on gut dysbiosis and inflammatory response. This study aimed to explore the efficacy and mechanism of?β-1,3-glucans-rich?E. gracilis?powder (EG) against high-fat-high-fructose (HFHF) diet-induced cognitive disorders in mice. A middle-aged (52-week-old C57BL/6J) mouse model with the following groups was adopted: HFHF, HFHF + EG, and control. At the end of the dietary intervention (8 weeks), cognitive behaviors, metabolic parameters, endotoxin levels, gut microbiota composition, and colon and brain pathology were examined. The results showed that EG supplementation attenuated HFHF-induced cognitive impairment, promoted synaptogenesis in the hippocampus, and improved synaptic ultrastructure. These beneficial effects were partly mediated through the upregulation of protein tyrosine phosphatase 1B (PTP1B)-recombinant insulin receptor substrate (IRS)-phosphorylated protein kinase B (p-AKT)-phosphorylated recombinant glycogen synthase kinase 3β (p-GSK3β)-microtubule associated protein tau (p-Tau) signaling. Furthermore, it prevented gut dysbiosis as evidenced by an increase in?β-diversity and enrichment of?Akkermansia?relative to the control group. EG supplementation was also able to partly reverse the HFHF-induced disruption of intestinal barrier, which was accompanied by reduced systemic and neuronal inflammation, normalized short-chain fatty acid production, and decreased serum lipopolysaccharide concentration. The findings from the present study support that?β-1,3-glucans-rich EG is a promising natural agent for the prevention of HFHF diet-induced deterioration in cognitive function that merits further investigation.

內(nèi)容: Two-dimensional luminescent metal-organic frameworks (2D LMOFs), have garnered significant attention for their unique fluorescent properties and highly accessible active sites, yet designing these LMOFs with target-dependent fluorescence for sensing remains a challenging endeavor. Herein, a zinc tetra(4-carboxyphenyl) porphine (Zn-TCPP) LMOF was prepared and first applied to the fast and sensitive sensing of tetracycline hydrochloride (TCH). Upon TCH exposure, the signature red fluorescence of Zn-TCPP at 609 nm diminishes, accompanied by the emergence of a 520 nm peak, which were originated from photo-induced electron transfer (PET) of Zn-TCPP to TCH and inner filter effect (IFE) of TCH towards Zn-TCPP, and the triggers of Zn-TCPP on the instinct fluorescence of TCH, respectively. Notably, the?I520 nm/I609 nm?fluorescence intensity ratio showed good linearity over a wide range of TCH concentrations (0.1?25 μmol/L), with a limit of detection (LOD) of 65.4 nmol/L. Additionally, the Zn-TCPP probe showed good TCH selectivity and anti-interference properties. The probe’s practicability was also validated by detecting TCH in spiked tap water, milk and chicken samples. Furthermore, test papers impregnated with the Zn-TCPP probe were prepared, allowing the visual detection of TCH with a smartphone. Results suggest the developed method is suitable for practical TCH detection.

內(nèi)容: Aging is one of the causes of cognitive dysfunction, which seriously affects people's quality of life. Unsaponifiable matter (USM) has antioxidant potential, but the molecular mechanisms that ameliorate aging and cognitive dysfunction are unknown. In this study, we used a galactose-induced brain aging mouse model and systematically analyzed the mechanism of USM in delaying aging in mice by detecting changes in serum and brain by metabolomics and transcriptomics. USM was compared with the model group, and non-targeted metabolomics identified 68 (15 up-regulated, 53 down-regulated) differentially metabolites, and transcriptomics identified 303 differentially expressed genes (228 up-regulated, 75 down-regulated). Combined multi-omics analyses showed that USM maintains normal brain function by regulating glycolytic processes, the tricarboxylic acid cycle (TCA), tryptophan metabolism, pyrimidine metabolism, the alanine, aspartate, and glutamate metabolism, and p38 mitogen-activated protein kinase (p38 MAPK) pathway. Meanwhile, USM increased neurotransmitter release from GABAergic synapses and cholinergic synapses by regulating synaptic vesicle cycling. In summary, USM increased energy metabolism and enhanced brain nerve signaling in the mouse brain, thereby delaying brain aging. This investigation offers novel perspectives into the molecular mechanism of USM to mitigate brain aging.

內(nèi)容: It has been suggested that immune senescence contributes to the aging of solid organs and that blocking immune senescence can alleviate the aging of organs. Aging is a systemic physiological change. It is currently difficult to achieve the goal of long-term delaying aging through drugs. Improving immunity and delaying aging through probiotics is a feasible research direction. Here, we first screened for a strain of?Lactobacillus kefiri?Fanghua (L.?kefiri-FH) derived from Tibetan kefir and confirmed its function in restoring immunosuppression. Spleen weight, thymus weight, and whole blood cells were restored. The expression of programmed cell death-ligand 1 (PD-1),?P16ink4a, and senescence-associated secretory phenotype (SASP)-related genes in the spleen and thymus was decreased. Second, we further confirmed the phenotype of?L.?kefiri-FH in improving solid organ function in 16-month-old mice as well as prolonging the lifespan of?Caenorhabditis elegans. Mechanistically, whole genome sequencing and metabolomic analysis indicated that?L.?kefiri-FH contained three genes related to bile acid metabolism and increased lithocholic acid (LCA) in the intestine. We also confirmed that LCA increased G-protein-coupled bile acid receptor (Gpbar5?or?TGR5) gene expression in dendritic cells (DCs) and inhibited the induction of T helper (Th) 1 and Th17 cells. Overall, our findings establish a causal relationship between the intestinal microenvironment, immune senescence, and solid organ aging, suggesting a way to regulate the intestinal microenvironment through diet, which thereby improves immune senescence and subsequently reduces solid organ aging.

內(nèi)容: Black rice, as a dietary supplement, has received increasing attention because of its beneficial health properties. Although black rice and its major ingredients have been considered a potential therapy for ulcerative colitis (UC), its effect and underlying mechanism of action remain obscure. In this study, black rice was demonstrated to improve dextran sulfate sodium salt (DSS)-induced UC and restore intestinal barrier dysfunction. Cyanidin 3-O-glucoside (C3G) is the most abundant ingredient in black rice. Similarly,?in vivo?and?in vitro?studies have demonstrated that C3G alleviates colitis and intestinal barrier dysfunction. Proteomic analysis showed that C3G significantly reduced abnormally elevated swiprosin-1 levels in mice with colitis. Furthermore, the effect of C3G on mitigating colitis was inhibited after swiprosin-1 was overexpressed in intestinal tissue?in vivo?and Caco-2 cells?in vitro. Acyl-CoA synthetase long-chain family member 1 (ACSL1) was identified as a potential protein that interacts with swiprosin-1 by co-immunoprecipitation and liquid chromatography-tandem mass spectrometry. By integrating metabolomics experiments and bioinformatics analysis of single-cell sequencing, ACSL1 was found to selectively bind to swiprosin-1 and regulate downstream linoleic acid metabolism in colitis. Moreover, C3G was observed to prevent the localization of ACSL1 within mitochondria via swiprosin-1, thereby inhibiting the oxidation of linoleic acid. This study demonstrated that C3G targeted swiprosin-1 to ameliorate UC via ASCL1-mediated linoleic acid metabolism, thereby providing a novel potential insight into the mechanism of C3G protection against colitis and establishing the groundwork for its clinical application.

內(nèi)容: Polycystic ovarian syndrome (PCOS) is the most principal reason for infertility in reproductive women, but no versatile treatment is feasible. Although?trans-10-hydroxy-2-decenoic acid (10H2DA) exhibits the anti-inflammatory, anti-cancerous and immunomodulatory properties, its role in improving PCOS remains elusive. This present study examined the effects of 10H2DA on the estrous cycle, ovarian morphology, reproductive hormone, glucose and insulin tolerances of PCOS mice, analyzed the binding between 10H2DA and free fatty acid receptor 4 (FFAR4), and explored the regulation of 10H2DA on the c-Jun N-terminal kinase (JNK)/JUN (Jun?proto-oncogene) signaling, cytosolic calcium ion (Ca2+), endoplasmic reticulum (ER) Ca2+?release, mitochondrial Ca2+, mitochondrial function, autophagy, lysosomal acidification, mitochondrial fission, secretion function and apoptosis of ovarian granulosa cells (GCs) using enzyme-linked immunosorbent assay, flow cytometry, Western blotting, molecular docking, various fluorescent probes or plasmid, etc. The results showed that 10H2DA alleviated the symptom of PCOS mice through improving the secretion dysfunction of GCs and protecting GCs against apoptosis. After binding to FFAR4 and inactivation of JNK/JUN signaling, 10H2DA restricted the release of ER Ca2+?through targeting ryanodine receptors (RYRs) which had been identified as the downstream targets of JUN, diminished cytosolic Ca2+?accumulation and prevented Ca2+?influx into mitochondria via adjusting the mitochondrial calcium uptake 1 and mitochondrial calcium uniporter. Concurrently, 10H2DA kept the integrity of mitochondrial function through maintaining mitochondrial Ca2+?homeostasis and suppressed the discharge of mitochondrial reactive oxygen species into the cytosol through blocking the mitochondrial permeability transition pore opening to avoid the lipid peroxidation and ameliorate the secretory function and apoptosis of GCs. Furthermore, 10H2DA rescued the defective autophagic flux along with the decline of autophagosomes and sequestosome 1 aggregation, restored the mitophagy flux with the abatement of mitophagosomes and Parkin recruitment to mitochondria, and accelerated the lysosomal degradation for depolarized mitochondria with the recovery of lysosomal acidification, whereas activation of JNK antagonized the amelioration of 10H2DA on above effectiveness, but this antagonism was counteracted by the attenuation of intracellular Ca2+. After application of 10H2DA, dynamin-related protein 1 phosphorylation was diminished and its recruitment to mitochondrial surface was impeded concomitant with the improvement of mitochondrial fragmentation, whereas inhibition of late-stage autophagy caused the failure of 10H2DA in improving mitochondrial fission. Collectively, 10H2DA might ameliorate PCOS mice through modulating autophagy-mediated mitochondrial fission dependent on the maintenance of Ca2+?homeostasis between ER and mitochondria.

內(nèi)容: Edible bird’s nest (EBN), abundant in sialic acid (SA) has been recognized as a natural substance beneficial to brain development and cognitive ability. In order to investigate active component of EBN, sialylated glycopeptides (SCP) were extracted from EBN by 60% ethanol after trypsin hydrolysis and its effects on central nervous system was evaluated in lipopolysaccharide (LPS)-induced neuroinflammation mice. EBN, SCP, and SA pretreatment and intervention reduced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in hippocampus and cortex, meanwhile inhibited the activation of microglia, astrogliosis and neuron apoptosis, which were consistent with the learning and memory improvement and anti-depression effects in behavioral tests. The counts of leukocytes, neutrophils and monocytes, as well as IL-1β, TNF-α, and IL-6 levels in peripheral circulation were significantly reduced by SCP. Results of plasma metabolomics suggested SCP up-regulated energy metabolism, promoted the recovery of primary and secondary bile acid metabolism and indole metabolism, where microbiota may involve. 16S rDNA sequencing of colonic contents showed EBN, SCP and SA repaired dysbacteriosis in LPS-treated mice by significantly up-regulating the anti-inflammatory Muribaculaceae and inhibiting pro-inflammatory related?Desulfovibrio?and?Candidatus_Saccharimonas. In addition, both EBN and SCP could significantly enrich?Aerococcus, while SA could specifically enrich Prevotellaceae_UCG_001. The gut-brain axis was preliminarily established, and SCP may have the potential to be a functional factor for neuroprotection applied in EBN industry.

內(nèi)容: The rise in life expectancies and gap between life span and health span necessitate innovative approaches, interventions, and food solutions to secure healthy aging. This study, conducted within the framework of the EAT4AGE project of the Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’, focuses on the rational design of functional foods for older adults. A co-extruded cereal prototype, fortified with two bioactive moieties, maca root powder and olive leaf extract, aims to address nutritional gaps identified in older adults, with a particular emphasis on high-quality and highly digestible proteins. Analytical determinations reveal the cereals have rich macronutrient profile exceeding 12% (m/m) protein, 20% (m/m) fat, and low sugar (< 5%,?m/m), surpassing commercially available products with texture analyses supporting improved hardness, reduced oral friction and oral comfort. An untrained consumer panel (n?= 21, age 73 ± 5) confirmed high palatability in various metrics and overall acceptability that were also affirmed through a trained sensory panel. Lastly, the product digestion was explored through an age-tailored?in vitro?digestion model which consistently demonstrated high protein digestibility, surpassing 80%, across all product formulations. Further, calculation of the?in vitro?digestible indispensable amino acid score of the product affirms its high nutritional quality. Thus, this study underscores the potential of designing palatable foods that could help promote a balanced and sustainable diet towards healthy aging.

內(nèi)容: Camellia oil, which contains a high content of triterpene alcohol, is known for a series of bioactivities including anti-inflammation. Amyrins are recognized as high bioactivity of anti-inflammation. However, no comparative study on triterpene alcohols from camellia oil. In this study, four high content triterpene alcohols from camellia oil, namely?β-amyrin,?ψ-taraxasterol, parkeol, and butyrospermol were evaluated through lipopolysaccharide induced RAW264.7 cell inflammation. The results showed that butyrospermol exhibited the highest anti-inflammatory activity, surpassing that of?β-amyrin. Characterization of signaling pathways showed that butyrospermol inhibited Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, suppressing the transcription of?Tlr4, expression of p65, NF-κB inhibitor α (IκBα), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and the phosphorylation of p65, IκBα, ERK, and p38. The anti-inflammatory effect of butyrospermol was further validated by phorbol 12-myristate 13-acetate induced mouse ear edema. The results in mouse showed that butyrospermol could inhibit the increase of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), p-JNK, p-p38, p-IκBα, and their corresponding mRNA levels. Our study provides new perspective on the anti-inflammatory role of different triterpene alcohols and explaining the bioactivity of camellia oil.