S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation.

Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks. During the last 4 weeks, SAM (16 mg/kg) was co-administrated with D-galactose. Behavior tests were used to assess cognitive function and depression-like behaviors of rats. Results showed that cognitive impairment and depression-like behaviors were reversed by SAM. SAM reduced neuronal cell loss, increased brain-derived neurotrophic factor level in the hippocampus, inhibited amyloid-ß level and microglia activation, as well as pro-inflammatory factors levels in the hippocampus and serum. Further, SAM enhanced antioxidant capacity and attenuated cholinergic damage by reducing malondialdehyde levels, increasing acetylcholine levels, expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the hippocampus. Above all, SAM has a potential neuroprotective effect on ameliorating cognitive impairment in brain aging, which is related to inhibition of oxidative stress and neuroinflammation, as well as α7nAChR signals. DATA AVAILABILITY: Data will be made available on request.

Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis.

BACKGROUND: Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. METHODS: In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. RESULTS: As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1ß, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. CONCLUSION: Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.

High-altitude Tibetan fermented milk ameliorated cognitive dysfunction by modified gut microbiota in Alzheimer's disease transgenic mice.

Alzheimer's disease (AD) is a complex neurodegenerative disease that is regarded as a growing global challenge. Accumulating evidence linking gut microbiota with AD has become intriguing. The purpose of this study was to investigate how Tibetan fermented milk affected memory impairment in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, using APP/PS1 transgenic mice as examples. We used Tibetan fermented milk (the yogurt samples with the highest microbial diversity were selected by 16S sequencing) as an intervention in such mice for 20 weeks, with aseptic maintenance feed as their basic diet. At the end of the intervention, we collected fecal samples for 16S ribosomal ribonucleic acid (rRNA) sequencing. We evaluated the effects of Tibetan fermented milk on the mice's cognitive function by behavioral examination, and deposition of amyloid beta (Aß) in the hippocampus and cortex of the mice by immunohistochemistry (IHC). Results showed that Tibetan fermented milk could improve cognitive impairment in APP/PS1 mice, including spatial learning/memory and object recognition/memory. Sequencing of 16S ribosomal RNA in mouse feces showed that Tibetan fermented milk increased intestinal microbial diversity and elevated the relative abundance of Bacteroides and Faecalibacterium spp. Mucispirillum and Ruminiclostridium were highly abundant in APP/PS1 mice. Additionally, correlation analysis revealed that cognitive function was correlated negatively with Mucispirillum abundance and positively with Muribaculum and Erysipelatoclostridium abundance. Tibetan fermented milk could also reduce deposition of Aß in the cerebral cortex and hippocampus. Our data suggested that long-term intake of Tibetan fermented milk had a beneficial effect on the composition of intestinal flora, which was correlated with cognitive improvements in APP/PS1 mice and seemed to help prevent and treat AD-induced cognitive decline.

In situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy.

Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π-π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.

Self-crosslinking and injectable hyaluronic acid/RGD-functionalized pectin hydrogel for cartilage tissue engineering.

In the present study, we developed a biomimetic injectable hydrogel system based on hyaluronic acid-adipic dihydrazide and the oligopeptide G4RGDS-grafted oxidized pectin, in which their hydrazide and aldehyde-derivatives enable covalent hydrazone crosslinking of polysaccharides. The hydrazone crosslinking strategy is simple, while circumventing toxicity, making this injectable system feasible, minimally invasive and easily translatable for regenerative purposes. By varying their weight ratios, the physicochemical properties of the mechanically stable hydrogel system were easily adjustable. Additionally, the preliminary studies demonstrated that chondrocyte behavior was dependent on HA/pectin composition and the presence of integrin binding moieties. Specifically, the incorporation of a certain amount of G4RGDS oligopeptide into HA/pectin-based hydrogels could serve as a biologically active microenvironment that supported chondrocyte phenotype and facilitated chondrogenesis. Furthermore, the hydrogel system exhibited acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable multicomponent hydrogel presented here is expected to be useful biomaterial scaffold for cartilage tissue regeneration.