內(nèi)容: Autism spectrum disorder (ASD) is a neurodevelopmental disorder influenced by genes and the environment. This study investigated the protective effects of bovine milk fat globule membrane (BMFGM) and goat milk fat globule membrane (GMFGM) supplementation on ASD model mice. Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM. Behavioral results indicated MFGMs ameliorated social deficits, with GMFGM being more effective. Milk fat globule membrane (MFGM) mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression, meanwhile GMFGM increased the anti-inflammatory factor interleukin (IL) -10. MFGMs also altered gut microbiota composition and maintained gut barrier integrity. Uniquely, GMFGM increased butyrate production. Correlation analysis revealed positive associations between social behavior, levels of phosphatidylcholine, sphingomyelin, and the abundance of Allobaculum, Clostridium_sensu_stricto, and Turicibacter. Overall, these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.

內(nèi)容: Alzheimer’s disease (AD) is a neurodegenerative disorder associated with brain aging, and the accumulation of β-amyloid (Aβ) and hyperphosphorylated Tau proteins are key pathological features. Currently, drugs for the treatment of AD are mainly single-targeted, but the complex pathogenesis of AD makes it difficult to achieve the desired results. Therefore, the development of multitargeted therapies is crucial for future interventions. Rice bran oil (RBO) has been recognized as an edible oil with several health benefits, but its effects on AD caused by brain aging remain underexplored. In this study, the effects of RBO on memory dysfunction in D-galactose (D-gal) mice and its molecular mechanisms were investigated via in vivo and in silico methods from the perspective of AD pathologies. Our results suggested that compounds in RBO could modulate the activities of Aβ precursor protein cleaving enzyme 1 (BACE1), mitogen-activated protein kinase 3 (MAPK3), matrix metalloproteinase 3 (MMP3), and intercellular adhesion molecule 1 (ICAM1), leading to inhibition of Aβ accumulation and Tau protein hyperphosphorylation. Moreover, RBO reduced Aβ-induced oxidative stress by inhibiting the activity of mouse double minute 2 homolog (MDM2) and cyclic adenosine monophosphate (cAMP) response element binding protein binding protein (CREBBP), and attenuated neuroinflammation by inhibiting the activity of nitric oxide synthase 2 (NOS2) and reducing Aβ accumulation and Tau protein hyperphosphorylation. Additionally, α-linolenic acid in RBO exhibited inhibitory effects on D-gal-induced apoptosis in PC12 cells through modulation of NOS2, MDM2, ICAM1, and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2). Similarly, stigmastanol inhibited apoptosis in D-gal-induced PC12 cells through the regulation of NOS2. Thus, RBO can be considered as a potential functional food to attenuate AD owing to its multicomponent and multitarget effects.

內(nèi)容: The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases, such as rheumatoid arthritis. Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L. (hemp) seeds, particularly hemp seed proteins. Therefore, this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins. To confirm the complete hydrolysis of hemp seed proteins during the fermentation process, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was employed. Further, the isolation and purification of peptides were achieved through ultrafiltration. The identity of peptides was nextly established using ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). The results revealed a total of 39 identified peptides in fermented hemp seeds, with 9 peptides selected based on their relative quantity. Notably, AAELIGVP (P1), AAVPYPQ (P2), VFPEVAP (P4), DVIGVPLG (P6), and PVPKVL (P9) demonstrated strong anti-inflammatory abilities in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. Molecular docking was used to understand the potential anti-inflammatory mechanism of these 5 peptides, and in silico results indicated that P1, P2, P4, P6, and P9 could bind to the active sites of toll-like receptor 4 (TLR-4), nuclear factor-κB (NF-κB), and inhibitor of NF-κB kinase (IKK) with higher binding energies. Overall, these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.

內(nèi)容: As one of the most common metabolic diseases, type 2 diabetes (T2D) has become a public health concern with rising global prevalence. Corni fructus (CF), a traditional Chinese herb utilized for centuries as homologous medicinal and food resources, has been widely used to treat glucose and lipid metabolism disorders. However, as a core active ingredient of CF, whether and how morroniside (MOR) improves T2D is still unclear. This study aimed to explore the pathways by which MOR ameliorates T2D in mice induced by high-fat diet (HFD) and low-dose streptozotocin through 16S rRNA gene sequencing. We found that MOR treatment significantly ameliorated body weight loss, hyperglycemia, hyperlipidemia and insulin resistance in T2D mice. In addition, MOR remarkably improved inflammation- and oxidative stress-driven hepatic and pancreatic injuries in the model mice. Mechanistically, MOR rehabilitated the dysregulated diversity and constitution of the gut microbiota in T2D mice, with significant changes in relative abundance in genus such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Lachnospiraceae_UCG-006 which are believed to be highly correlated with serum parameters and insulin resistance in mice with T2D. Therefore, we infer that MOR improves T2D at least partially by maintaining the host microbiota homeostasis, and MOR may be a promising candidate for T2D treatment.

內(nèi)容: Rosa roxburghii seeds are by-products of R. roxburghii processing, and their protein hydrolysates (RTSPHs) were found to possess a variety of biological activities. This study aimed to rapidly identify pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory peptides in RTSPHs and to elucidate their molecular mechanisms by combining peptidomics and virtual screening. The simulated intestinal environment worsened the peptide’s inhibition of PL but catalyzed the inhibition of CE. The fraction less than 3 kDa in RTSPHs was found to have the highest PL/CE inhibitory activity, among which 17 promising inhibitory peptides were identified and screened by peptidomics and virtual screening. LFCMH, RIPAGSPF, and YFRPR showed good inhibitory abilities against both PL and CE. Molecular docking showed that peptides inhibited PL and CE mainly by hydrogen bonding and hydrophobic interactions with residues in the active site and surface loop. Inhibition kinetic revealed that the peptides were competitive and mixed-type inhibitors of PL/CE. Further, the three peptides, LFCMH, RIPAGSPF, and YFRPR, could effectively inhibit 3T3-L1 preadipocytes differentiation, increase high-density lipoprotein cholesterol content and decrease low-density lipoprotein cholesterol content. This study suggests that combining peptidomics with virtual screening is an effective strategy for rapid screening of PL/CE inhibitory peptides.

內(nèi)容: Alzheimer’s disease (AD) has become an important public health issue worldwide. p-Coumaric acid (CA) and lactoferrin (Lf) possessed antioxidant, anti-inflammatory, and anti-AD activities. Herein, we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms. Twelve-week-old amyloid precursor protein (APP)/presenilin 1 (PS1) mice were treated with CA, Lf, or both CA and Lf for 8 weeks. Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees, with stronger effects for combined intervention than for CA or Lf alone. Specifically, combined treatment was most effective in improving nesting ability and reducing amyloid β1?42 (Aβ1?42) deposition in mice. Moreover, combined treatment was more effective in suppressing APP, β-site APP cleavage enzyme 1, and inflammation; it inhibited the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon; it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae, Lachnospira, and Eubacterium at the genus level. Overall, the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.

內(nèi)容: Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein (ox-LDL) particles, a process that induces atherothrombosis. Sulforaphane (SFN) is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities. The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo. Using a series of platelet functional assays in human platelets in vitro, we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation (surface CD62P expression). Mechanistically, studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36- mediated activation of Src kinases, leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling, and resultant inhibition of NADPH oxidase 2 (NOX2) -dependent generation of reactive oxygen species (ROS). Moreover, 12-week supplementation of SFN-enriched broccoli sprout extract (BSE, 0.06% diet) in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity. Studies using pharmacological inhibitors of CD36, protein kinase A (PKA) and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling. Thus, through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity, SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.

內(nèi)容: The aromatic Baeckea frutescens leaves (BFL) known as “Gang-Song-Cha” is a popular drink (Tea) in South China. To explore the healthcare value, a systematic and in-depth study on BFL alleviating rheumatoid arthritis (RA) was carried out by integrating network pharmacology, molecular docking, and experimental verification. The efficacy was first evaluated, and the BFL extract could ameliorate RA by inhibiting articular swelling, lowering immune organ index, improving the ankle pathologies, and regulating serum levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-10 in CIA rats. Then the anti-RA mechanism of BFL was investigated by leveraging the high-content and active component 5-hydroxy-7-methoxy-2- isopropylchromone (Chro), and the potential signaling pathway and related target proteins for Chro acting on RA were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and docking simulation. Finally, the experimental validations were conducted on rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), and compound Chro could inhibit cell invasion and migration, block cell cycle at G2/M phase and induce apoptosis, and reduce the secretion of inflammatory cytokines by suppressing the PI3K-Akt pathway. These results provided pharmacological basis for the folk usage of “Gang-Song-Cha” for intervening RA.

內(nèi)容: Cadmium accumulation in seafood has become a major concern for human health. Recently, there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots (CDs) that are formed during the thermal processing of seafood. The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming. In addition, it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms, thereby, they could influence the bioavailability of metal ion. While there have been numerous studies on the toxic effects of cadmium or CDs, none have explored the combined toxicity of food-borne CDs from clams (CCDs) and Cd2+. In this study, we investigated the single or co-exposure (combined exposure) of Cd2+ and CCDs on PC12 cells to investigate the combined toxicity of them. Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd2+ . More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd2+ and CCDs led to significant metabolic disorders, causing an antagonistic effect on energy metabolism, and a synergistic effect on amino acids and lipids metabolism. The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure. These findings provide new evidence that support the enhanced cytotoxicity of Cd2+ by the CCDs derived from the thermal processing of clams. This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.

內(nèi)容: Areca nut is the basic ingredient of betel quid, which is chewed by hundreds of millions of people in South- Eastern Asia. Chewing of areca nut has been associated with oral cancers potentially due to its specific alkaloids, among which arecoline constitutes about 90% of total fraction. Being the world’s fourth most commonly used psychoactive substance, arecoline evokes stimulation, addiction, and other direct neurological effects, while its misuse correlates to neurotoxic effects. However, what might underlie its neurotoxic mechanisms has been poorly documented. The brain is encoded by a complex network of neuronal and glial cell types, and neurotoxicity of hazardous compounds present transcriptional heterogeneity. Recently, the eusocial bumblebee has been used as a model for studying brain effects, with sophisticated cognitive capability and precisely measured brain architecture. Here, we decipher cell-type-specific mental risks to arecoline using bumblebees. Arecoline induced locomotor hyperactivity and cognitive impairment. Single nucleus RNA sequencing (snRNA-seq) unearthed arecoline-induced cell-specific responses, primarily targeted on Kenyon cells (KC). Moreover, high-dose arecoline induced distinctive cell responses among KC subtypes, particularly class I large Kenyon cell (lKC), leading to DNA damage, excitatory/inhibitory (E/I) imbalance, and calcium dyshomeostasis, which potentially resulted in cognitive impairment. Given arecoline’s popularity and growing exposure risks to humans, neurological health risks of areca nut warrant serious consideration.