內容: The effective intervention strategy for autism spectrum disorder (ASD) are currently limited. Herein, we attempted to evaluate the potential of L-proline (Pro), a multifunctional amino acid, in ameliorating autism-like behaviors and clarify the molecular mechanisms involved by using the typical valproic acid (VPA)-induced mouse model of ASD. Pro significantly attenuates repetitive behaviors and social dysfunction in ASD mice. The correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and composition. The histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex (PFC) induced by VPA exposure. RNA sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease, neuroactive ligand-receptor interaction, oxidative phosphorylation, and mitogen activated protein kinase signaling pathway. Overall, dietary Pro supplementation may be a promising intervention strategy for ASD.

內容: Methionine restriction (MR) is an effective dietary strategy to regulate energy metabolism and alleviate oxidative stress and inflammation in the body, especially in the middle-aged and elderly population. However, the high methionine content of meat products makes this dietary strategy impossible to combine with protein supplementation and MR. Highland barley (HB), a low-methionine cereal, not only provides the body with protein but also has improved glucose metabolism and antioxidant and anti-inflammatory properties. Therefore, this study evaluated the feasibility of HB as a source of methionine-restricted dietary protein and the potential mechanisms. Middle-aged C57BL/6J mice were fed a control diet (CON), a high-fat diet (HFD), a whole-grain HB high-fat diet (HBHF), or a HBHF + methionine diet (HBHFmet) for 25 weeks. The results showed that the HBHF could keep the body weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, inflammation, and oxidative stress of HFD mice at normal levels. Compared with the HFD groups, HBHF inhibited pancreatic cell apoptosis and improved insulin secretion while improving hepatic and skeletal muscle glucose metabolism. However, these efficacies were attenuated in HBHFmet group mice. These findings suggest that HBHF has an MR strategy.

內容: Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a “disease”. Brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning emerge as a potential strategy of anti-obesity by dissipating energy as heat. However, drugs based on adipose tissue thermogenesis have not been successfully approved yet. In current study, we found that black tea extract (BTE) obtained by patent-authorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity, improvement of adipose distribution, and glucose metabolism improvement in diet-induced obesity mice. Mechanismly, anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1 (UCP1), especially visceral adipose tissue (VAT) with browning resistance. Specifically, utilizing in silico approach of network pharmacology and molecular docking, we identified carbonic anhydrase 2 (CA2) in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B (Akt) signaling pathway linked CA2 and UCP1. Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation. Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway, which could be developed as promising anti-obesity agent with good safety and efficacy.

內容: The present study reports the structural characteristics of 3 polysaccharide fractions (SPS-F1, SPS-F2 and SPS-F3) isolated and purified from squash. SPS-F1 (molecular weight (Mw) = 12.30 kDa) and SPS-F2 (Mw = 19.40 kDa) were likely to contain HG and RG-I domain of pectic polysaccharide, respectively. SPS-F2 (Mw = 270.4 kDa) was mainly composed of rhamnose, galactose and arabinose. The treatment with SPS decreased body weight gain, glucose and TG levels in type 2 diabetes rats. Besides, 25 differential metabolites were identified based on urinary metabolomics analysis, which are crucial to the anti-diabetic effect of SPS. The regulation of nicotinamide N-oxide, histamine, cis-aconitate, citrate, L-malic acid, 3-(3-hydroxyphenyl) propanoic acid and N-acetyl-L-aspartic acid were mainly associated with energy metabolism, gut microbiota and inflammation. Study of surface plasmon resonance revealed the binding kinetics with galectin-3 (Gal-3) and fibroblast growth factor 2 (FGF2). The KD values of SPS-F2 and SPS-F3 to Gal-3 were 4.97 × 10-3 and 1.48 × 10-3 mol/L, indicating a weak binding affinity. All 3 fractions showed moderate binding to FGF2 and the affinity was SPS-F3 > SPS-F2 > SPS-F1. Thus, the metabolomics and SPR approach were proved to be a promising tool in exploring the anti-diabetes effects of SPS and provided a deep understanding of the mechanisms.

內容: As the body’s internal clock, the circadian rhythm regulates the energy expenditure, appetite, and sleep. There exists a close relationship between the host circadian rhythm and gut microbiota. In this work, a circadian disorder mouse model induced by constant darkness (CD) was constructed to investigate the regulating effects of capsaicin (CAP) on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms. Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue. The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP. Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness, diversity and composition, and restored diurnal oscillations of gut microbes at the phylum and family level. These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice, providing theoretical basis for CAP to be used as a muti-functional ingredient with great health-promoting effects.

內容: In recent years, the allergy rate of oysters has surged, and daily food processing methods make it hard to reduce heat resistance and digestive allergy such as tropomyosin (TM). In this study, the Maillard reaction with xylose significantly reduced the IgE binding capacity of Alectryonella plicatula food matrix (AFM), that reduced by (77.81 ± 2.68)%. The study found the Maillard reaction changes the structure of the AFM, in which the content of α-helix decreased by (24.64 ± 1.46)%. Structural transformation further explains why the Maillard reaction alters the immunobinding activity of AFM. In addition, the Maillard reaction reduces the digestive stability of the AFM and makes TM in the A. plicatula food matrix Maillard reaction products (AFM-MRPs) more easily digested. Based on the above research, 10 amino acids on the 7 IgE epitopes of TM were modified. This result indicates that the Maillard reaction reduces the immunobinding activity of the AFM by changing the structure and modifying the amino acids on the epitope.

內容: Diabetes-associated cognitive dysfunction has already been attracted considerable attention. Advanced glycation end products (AGEs) from daily diets are thought to be a vital contributor to the development of this diseases. However, the effect of one of the best-characterized exogenous AGEs Nε-(carboxymethyl)lysine (CML) on cognitive function is not fully reported. In the present study, diabetical Goto-Kakizaki (GK) rats were treated with free CML for 8-weeks. It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test. In details, exogenous CML increased levels of oxidative stress, promoted the activation of glial cells in the brain, up-regulated the release of inflammatory cytokines interleukin-6, inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation. Furthermore, exogenous CML promoted the amyloidogenesis in the brain of GK rats, and inhibited the expression of GLUT4. Additionally, several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate, succinic acid, glutamine, glutamate were significantly changed in brain of GK rats treated with exogenous free CML. In conclusion, exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation, energy and neurotransmitter amino acid homeostasis.

內容: Translesion DNA synthesis (TLS) can bypass DNA lesions caused by chemotherapeutic drugs, which usually result in drug resistance. Given its key role in mutagenesis and cell survival after DNA damage, inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin (CDDP), a widely used anticancer agent. Unfortunately, few suitable natural TLS inhibitors have been reported. Here, we found that a triterpenoid compound Ganoboninketal C (26-3) from Ganoderma boninense, a traditional Chinese medicine, can impair CDDP-induced TLS polymerase eta (Polη) focus formation, PCNA monoubiquitination as well as mutagenesis. Moreover, 26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure. Interestingly, 26-3 can also sensitize tumor cells to Gefitinib therapy. Mechanistically, through RNA-seq analysis, we found that 26-3 could abrogate the CDDP-induced upregulation of Polη and PIDD (p53-induced protein with a death domain), 2 known factors promoting TLS pathway. Furthermore, we found that activating transcription factor 3 is a potential novel TLS modulator. Taken together, we have identified a natural TLS inhibitor 26-3, which can be potentially used as an adjuvant to improve clinical efficacy.

內容: The cold plasma (CP) technique was applied to alleviate the contamination of polycyclic aromatic hydrocarbon (PAH) in this investigation. Two different CP treatments methods were implemented in the production of beef patties, to investigate their inhibition and degradation capacity on PAHs. With 5 different cooking oils and fats addition, the inhibition mechanism of in-package cold plasma (ICP) pretreatment was explored from the aspect of raw patties fatty acids composition variation. The results of principal component analysis showed that the first two principal components accounted for more than 80% of the total variation in the original data, indicating that the content of saturated fatty acids was significantly positively correlated with the formation of PAHs. ICP pretreatment inhibited the formation of PAHs by changing the composition of fatty acids, which showed that the total amount of polyunsaturated fatty acids decreased and the total amount of monounsaturated fatty acids increased. Sensory discrimination tests demonstrated there were discernable differences between 2 CP treated samples and the controls, utilization of the ICP pretreatment in meat products processing was expected to achieve satisfying eating quality. In conclusion, CP treatment degraded PAHs through stepwise ring-opening oxidation in 2 reported pathways, the toxicity of PAHs contaminated products was alleviated after CP treatment.

內容: Recent research on the genome of Bifidobacterium bifidum has mainly focused on the isolation sources (intestinal tract niche) recently, but reports on the isolation region are limited. This study analyzed the differences in the genome of B. bifidum isolated from different geographical populations by comparative genomic analysis. Results at the genome level indicated that the GC content of American isolates was significantly higher than that of Chinese and Russian isolates. The phylogenetic tree, based on 919 core genes showed that B. bifidum might be related to the geographical characteristics of isolation region. Furthermore, functional annotation analysis demonstrated that copy numbers of carbohydrate-active enzymes (CAZys) involved in the degradation of polysaccharide from plant and host sources in B. bifidum were high, and 18 CAZys showed significant differences across different geographical populations, indicating that B. bifidum had adapted to the human intestinal environment, especially in the groups with diets rich in fiber. Dietary habits were one of the main reasons for the differences of B. bifidum across different geographical populations. Additionally, B. bifidum exhibited high diversity, evident in glycoside hydrolases, the CRISPR-Cas system, and prophages. This study provides a genetic basis for further research and development of B. bifidum.