内容: Epidemiological studies have reported varying associations between coffee consumption and bone mineral density. This study aims to systematically asses the pharmacological effects of prolonged coffee intake on osteoblasts, osteoclasts, and postmenopausal osteoporosis induced by ovariectomy. In vitro, experiments revealed that coffee water extract upregulated the expression of osteogenic-related proteins such as 12.5 μg/mL middle concentration group had a 1.33 fold increase in collagen type Ⅰ α 1 (COL1A1) expression, and a 1.83 fold increase in Osterix expression by inhibiting the phosphorylation of protein kinase B (AKT), inhibitor of κB protein-α (IκBɑ), P65, and extracellular signal-regulated kinase (ERK). Additionally, it inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis in RAW264.7 cells though the AKT, MAPKs, and NF-κB pathways, concomitant with the inhibition of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1. In vivo studies demonstrated that a medium-dose coffee sample inhibited osteoclastogenesis, stimulated osteogenesis, and ameliorated bone loss in ovariectomized mice. Molecular docking analysis validated the impact of caffeine, cholorogenic acids, and trigonelline on bone homeostasis. In summary, consumption of 4?5 cups of coffee per day in humans may attenuate ovariectomy (OVX)-associated pathological bone loss by disrupting osteoclast activity and promoting osteogenesis, while long-term consumption of high-dose coffee could disrupt bone homeostasis.

内容: This study investigated the hepatotoxic effects and mechanisms of high-dose tea polyphenols on zebrafish liver based on the gut-liver axis theory. An 8-week rearing experiment evaluated various aspects such as physiological and biochemical indicators, histology, gut microbiota, and liver transcriptomics of zebrafish. The results showed that feeding zebrafish a diet rich in high-dose tea polyphenols disrupted their hepatic lipid metabolism, ultimately causing liver damage. Tea polyphenols regulated signaling pathways related to “lipid metabolism and absorption” and “fatty acid degradation”, promoting the uptake of fatty acids and cholesterol by liver cells, inhibiting fatty acid oxidation and excretion, and causing liver fat accumulation. Additionally, high-dose tea polyphenols altered the composition of the gut microbiota, reducing microbial diversity and decreasing the production of intestinal short-chain fatty acids (SCFAs). As a result of the gut-liver axis interaction, low levels of SCFAs and harmful bacteria from the intestine were able to enter the liver through the portal vein, activating hepatic pro-inflammatory factors and causing liver inflammation. The accumulation of liver fat further promoted the expression of pro-inflammatory factors and transported them to the intestine through the bile duct, exacerbating intestinal damage in zebrafish. Therefore, caution should be exercised when using tea polyphenols as a nutritional supplement or medication, especially at high doses and with long-term use, to be aware of their potential adverse effects.

内容: Impairment of cardiomyocyte mitochondrial function caused by pressure overload is a central event in the development of cardiac hypertrophy (CH). Gentianella acuta Hulten, widely consumed as an herbal tea alternative by the Mongolian and Ewenki hunters, has demonstrated significant protective effects on cardiovascular. However, the bioactive components responsible for the medicinal efficacy of G. acuta, as well as the mechanisms underlying its anti-CH effects, remain incompletely understood. In the present study, we demonstrate that Gen-miR-5, isolated from G. acuta, effectively mitigates angiotensin Ⅱ induced CH. Mechanistically, Gen-miR-5 suppresses the sustained activation of yes-associated protein (YAP) by downregulating platelet isoform phosphofructokinase, thereby disrupting the YAP/p300/histone deacetylase 6 (HDAC6) interaction and subsequently reducing lactylation at the HDAC6 K901 site. Moreover, Gen-miR-5 curtails lactate accumulation in cardiomyocytes, further diminishing lactylation at this site. These processes collectively contribute to the alleviation of mitochondrial oxidative stress, the restoration of mitochondrial membrane potential, and the stabilization of mitochondrial dynamics, thus inhibiting myocardial hypertrophy. These findings highlight the therapeutic potential of miRNAs derived from G. acuta in treating cardiac remodeling diseases and clarify the molecular mechanisms of their cardioprotective effects.

内容: Glyphosate is widely used in agriculture, and its residues accumulate in soil and water, which adversely affects human health. The existing colorimetric methods for glyphosate detection are usually achieved by inhibiting the catalytic activity of natural enzymes or nanozymes, and often require the participation of easily decomposable H2O2, leading to unstable detection capabilities or even false positive results. This article reports a smartphone-assisted sensor for colorimetric detection of glyphosate in several food samples based on enhancing the laccase-like activity of cubic Ag2O nanoparticles. Glyphosate can significantly enhance the generation of radicals and electron transfer in cubic Ag2O reaction solution, causing an obvious change in the color of the system, which can be easily distinguished by naked eye. The established sensor has excellent detection performance, with limit of detection as low as 2.09 μg/L, and it is highly selective to other competitive substances. The method of enhancing the enzyme-mimic activity of nanomaterials to detect glyphosate residues is proposed for the first time, which can avoid false positive results caused by traditional enzyme inhibition methods and complex food matrices. Moreover, smartphones can simplify the conventional analysis procedure and achieve convenient on-site monitoring of glyphosate pesticides in food.

内容: Interactions between proteins/peptides and polyphenols have been widely investigated to improve their properties and functions. Previous studies have shown that covalent and non-covalent products exhibit different structural and bioactivity characteristics. The pentapeptide PAYCS (PS) was reported to be neuroprotective in amnesia mice, and catechin (CA) conjugation could improve its activity. However, different mechanisms on memory deficits alleviation between covalent and non-covalent conjugates were little investigated. In this study, the structure of PS-CA (PS and CA covalent conjugates) and PS+CA (PS and CA non-covalent complex) was characterized by using HPLC-MS/MS. Single peak for newly formed compound was identified in PS-CA and modification of tyrosine (Tyr) and cystine (Cys) was observed. In the APP/PS1 transgenic mice model experiments, behavioral tests showed that PS-CA and PS+CA could both exhibit better memory enhancing effects than that of PS. The 16S rRNA results mainly showed the alteration of gut microbiota, especially the changes in the Bacteroidota/Firmicutes ratio and significant changes in the abundance of Verrucomicrobiota. Additionally, the treatments of PS+CA and PS-CA could primarily regulate the contents of certain short chain fatty acids (SCFAs) and brain neurotransmitters, respectively. The quantitative polymerase chain reaction (qPCR) results indicated that the cholinergic system, neuronal apoptosis, and partial antioxidant pathways could be also regulated by both the treatment of PS-CA and PS+CA. Correlation analysis confirmed the relationship between the abundance of Verrucomicrobiota and other factors. The serum peptidomes results revealed that PAY contained peptides were mostly identified in PS+CA group. Especially, PS+CA showed better effects on regulating certain SCFAs and 5-hydroxytryptamine (5-HT) related neurotransmitters while PS-CA exhibited better alleviation effects on behavioral tests and neuroprotection. All these results suggested that covalent and noncovalent modification of PS with CA showed different neuroprotective effects.

内容: This study aimed to develop a submicron emulsion (SE) of Acer truncatum seed oil (ASO) and Rose roxburghii Tratt juice (RRTJ) using a response surface method for optimal formula screening and process parameters. The stability of ASO-RRTJ/SE and its effects on scopolamine-induced memory impairment in mice were investigated. The ASO-RRTJ/SE exhibited a desirable particle size ((276.86 ± 4.61) nm), polydispersity index (PDI, 0.22 ± 0.02), centrifugal stability parameter (Ke, 0.143 ± 0.004), and Zeta potential ((30.57 ± 2.38) mV). Morris water maze test, measurement of acetylcholine (ACh) concentration and acetylcholinesterase (AChE) activity in the hippocampus, superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in serum, hematoxylin and eosin (H&E) staining, immunofluorescence staining were adopt to evaluate ASO-RRTJ/SE therapeutic potential in alleviating scopolamine-induced memory impairment in mice. Behavioral tests demonstrated that ASO-RRTJ/SE significantly ameliorated scopolamine-induced spatial learning and memory deficits in mice, suggesting potential neuroprotective effects against scopolamine-mediated central nervous system excitation. Compared to the Model group, the high-dose ASO-RRTJ/SE (H-SE) group displayed a 77.84% increase in hippocampal ACh content, a 46.97% decrease in AChE activity, a 29.48% increase in serum SOD activity, and a 40.15% decrease in MDA content. H&E staining of hippocampal sections revealed that the H-SE group exhibited well-organized hippocampal neurons, with a significantly reversal of nuclear pyknosis, deep staining, and cytoplasmic dissolution. The pyramidal cell layer displayed improved organization, and the intercellular distance returned to normal. Additionally, H-SE treatment significantly reduced the aggregation of phosphorylated tau protein, increased choline acetyltransferase expression, and promoted brain-derived neurotrophic factor production. In conclusion, ASO-RRTJ/SE ameliorates scopolamine-induced memory impairment in mice.

内容: One novel enzymatic-extractable polysaccharide (ES1) from fruiting bodies of Laetiporus sulphureus was obtained by isolation and purification using a DEAE Seplife FF chromatographic column and a Sephacryl S-400HR column. The hepatoprotective ability of ES1 against chronic alcoholic liver disease (ALD) and its underlying mechanism were explored. The results indicated that ES1 could alleviate liver damage in ALD mice by activating sequestosome-1/nuclear factor E2-related factor 2 (P62/Nrf2) pathway to increase antioxidant enzyme activities against oxidative stress, regulating adenosine monophosphate-activated protein kinase (AMPK) pathway to promote fatty acid oxidation and inhibit cholesterol synthesis against lipid metabolism disorders, and improving gut microbiota (increasing the relative abundances of Ligilactobacillus and Akkermansia, and reducing the relative abundances of Enterococcus, Romboutsia, Allobaculum, Coriobacteriaceae_UCG-002, Dubosiella and Faecalibaculum) against intestinal barrier dysfunction. Meantime, structural analysis showed that ES1 with molecular weight of 25.79 kDa was composed of α-D-Manp-(1→, →2,6)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →3)-α-L-Fucp-(1→, and α-D-Glcp-(1→, and its structure was also inferred. Therefore, these data support the application of ES1 as a potential functional food or drug for treating ALD.

内容: In our previous study, a synbiotic AHY improved constipation was developed using 3 probiotic strains Lactiplantibacillus plantarum Y12, AHQ-14 and HM22) and four prebiotics (stachyose, fructooligosaccharides, isomaltooligosaccharide and galactooligosaccharides). The in vitro cholesterol-scavenging capacity of 3 probiotic strains was assessed, revealing that AHY may possess lipid-lowering potential. Consequently, the in vivo lipid-lowering efficacy of AHY was evaluated by establishing a hyperlipidemia model using high-fat diet (HFD)-fed C57BL/6J mice and administering AHY over a period of 12 weeks. Various parameters including biochemical indexes, histological morphology, metabolites, gene expression and intestinal flora were analyzed to evaluate the hypolipidemic effect of AHY in vivo. The results demonstrated that gavage administration of AHY led to a significant reduction in body weight and organ indexes, as well as an improvement in lipid abnormalities in serum. Moreover, AHY significantly reduced serum total bile acids (TBAs) and significantly increased fecal TBAs. Furthermore, AHY up-regulated tight junction proteins (claudin-1, ZO-1, occludin) and down-regulated inflammatory factors (interleukin-6, interleukin-1β, tumor necrosis factor-α), enhancing intestinal barrier function and reducing colon inflammation. Additionally, AHY influenced the composition of gut microbiota by increasing beneficial bacteria (Lactobacillus, Bifidobacterium) and decreasing harmful bacteria (norank_f_Desulfovibrionaceae, norank_f_Oscillospiraceae), resulting in higher level of short-chain fatty acids (SCFAs) in the gut. This modulation of bacterial flora contributed to the regulation of cholesterol metabolism through activating the gut-liver axis pathway, effectively reducing blood lipid levels. These findings suggest that AHY have the potential to be a functional synbiotic for alleviating hyperlipidemia and offers novel insights to understand the mechanism for probiotic products alleviating hyperlipidemia.

内容: Sunflower, a key agricultural crop with a history of use in Chinese medicine, holds potential for hyperuricemia treatment. This study investigates the efficacy and mechanisms of flavonoids extracted from sunflower receptacles in managing hyperuricemia. Various ethanol extracts were tested in hyperuricemia rats to evaluate their effects on uric acid reduction, joint swelling alleviation, and liver and kidney damage. The 30% ethanol extract showed the most significant effects, reducing uric acid levels, alleviating joint swelling, and minimizing liver and kidney damage. Liquid chromatography-mass spectrometry analysis identified 16 active flavonoid compounds in this extract. Molecular docking and machine learning analysis identified quercetin as the strongest xanthine oxidase (XO) inhibitor, with apigenin 7-glucoside emerging as a novel candidate. Further computational studies, including Gaussian accelerated molecular dynamics simulations, energy landscape analysis, and Markov state models, revealed a similar XO inhibition mechanism to allopurinol for quercetin. Our findings underscore the therapeutic potential of sunflower receptacle flavonoids for hyperuricemia management. This research paves the way for incorporating sunflower-derived flavonoids into modern pharmacological approaches for hyperuricemia treatment.

内容: Benzalkonium chloride (BAC) is an effective disinfectant against Salmonella and widely used in the food industry. However, there are growing concerns about the risk of inducing Salmonella to produce cross-resistance to antibiotics resulting from the excessive use of BAC. In this study, 50 foodborne Salmonella isolates were exposed to sub-inhibitory concentrations of BAC. It was demonstrated that 7 isolates showed direct resistance to BAC, and 35 isolates showed cross-resistance to at least one of 10 tested antibiotics. Among these 35 isolates, 15 isolates exhibited an increase in minimum inhibitory concentration (MIC) for tetracycline, followed by 11 isolates for kanamycin and 9 isolates for ampicillin. Salmonella Enteritidis SJTUSM06 with the highest increase in MIC of tetracycline (from 4 to 32 μg/mL) was selected for further study. Tandem mass tag-labeled proteomics was used to determine key proteins involved in development of cross-resistance to tetracycline in BAC-adapted S. Enteritidis. It was identified that there were 146 differentially expressed proteins, including 95 up-regulated and 51 down-regulated proteins, most of which were involved in carbohydrate and lipid metabolism, ribosomes, transporters, virulence, motility, and stress response pathways. The efflux pump AcrB was significantly upregulated by 2.03-fold in BAC-adapted S. Enteritidis. It was also demonstrated that efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PaβN) decreased the MIC of tetracycline in BAC-adapted S. Enteritidis from 32 to 8 μg/mL, indicating that active efflux pump played an important role in the development of resistance to tetracycline induced by BAC. Deletion of acrB resulted in a decrease in the resistance to tetracycline in BAC-adapted S. Enteritidis. Compared with the parent strain, MIC for tetracycline in ΔacrB mutant was 16 μg/mL with a 2-fold decrease. These results demonstrated that AcrB played a positive role in the development of cross-resistance to tetracycline after adaptation of S. Enteritidis to BAC.