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Molecular Neurobiology Feb 2024Accumulating evidence has suggested that the gut microbiome plays an important role in depression. Akkermansia muciniphila (AKK), a next-generation probiotic, shows a...
Accumulating evidence has suggested that the gut microbiome plays an important role in depression. Akkermansia muciniphila (AKK), a next-generation probiotic, shows a beneficial effect on immune and metabolic homeostasis. The relative abundance of AKK was found negatively correlated with depressive symptoms in both clinical and pre-clinical studies. To evaluate the potential antidepressant effect of AKK and explore the possible mechanism, we used chronic alcohol exposure and chronic unpredictable mild stress (CUMS) to induce depressive-like behaviors in mice. We found that oral AKK administration significantly reduced the immobility time in the force swimming test (FST) and tail suspension test (TST) in the mice with chronic alcohol exposure and the CUMS mice. The sucrose preference in the mice receiving AKK was significantly increased in the sucrose preference test (SPT). More importantly, AKK implantation significantly increased the level of 5-HT in the gut and PFC of both the alcohol exposure mice and the CUMS mice. Furthermore, AKK had inhibited the expression of SERT in the gut but not in the brain for both NIAAA and the CUMS model mice. Interestingly, the expression of cFos in enteric nerves in the gut significantly decreased after AKK administration. In conclusion, our study demonstrated the antidepressant effect of AKK in mice exposed to alcohol exposure and CUMS, with the potential mechanism that AKK implantation might lead to an increased level of 5-HT and inhibited SERT expression in the gut, and might alter the gut-to-brain signal through suppression of enteric nerves activation.
Topics: Mice; Animals; Depression; Serotonin; Brain; Antidepressive Agents; Sucrose; Stress, Psychological; Disease Models, Animal; Hippocampus; Akkermansia
PubMed: 37668965
DOI: 10.1007/s12035-023-03602-6 -
ELife Aug 2023Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of...
Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of neural activity. Here, we present OHRBETS (Open-Source Head-fixed Rodent Behavioral Experimental Training System; pronounced 'Orbitz'), a low-cost, open-source platform of hardware and software to flexibly pursue the neural basis of a variety of motivated behaviors. Head-fixed mice tested with OHRBETS displayed operant conditioning for caloric reward that replicates core behavioral phenotypes observed during freely moving conditions. OHRBETS also permits optogenetic intracranial self-stimulation under positive or negative operant conditioning procedures and real-time place preference behavior, like that observed in freely moving assays. In a multi-spout brief-access consumption task, mice displayed licking as a function of concentration of sucrose, quinine, and sodium chloride, with licking modulated by homeostatic or circadian influences. Finally, to highlight the functionality of OHRBETS, we measured mesolimbic dopamine signals during the multi-spout brief-access task that display strong correlations with relative solution value and magnitude of consumption. All designs, programs, and instructions are provided freely online. This customizable platform enables replicable operant and consummatory behaviors and can be incorporated with methods to perturb and record neural dynamics in vivo.
Topics: Mice; Animals; Conditioning, Operant; Reward; Behavior, Animal; Sucrose; Consummatory Behavior
PubMed: 37555578
DOI: 10.7554/eLife.86183 -
Applied Microbiology and Biotechnology May 2024Whey is a byproduct of dairy industries, the aqueous portion which separates from cheese during the coagulation of milk. It represents approximately 85-95% of milk's... (Review)
Review
Whey is a byproduct of dairy industries, the aqueous portion which separates from cheese during the coagulation of milk. It represents approximately 85-95% of milk's volume and retains much of its nutrients, including functional proteins and peptides, lipids, lactose, minerals, and vitamins. Due to its composition, mainly proteins and lactose, it can be considered a raw material for value-added products. Whey-derived products are often used to supplement food, as they have shown several physiological effects on the body. Whey protein hydrolysates are reported to have different activities, including antihypertensive, antioxidant, antithrombotic, opioid, antimicrobial, cytomodulatory, and immuno-modulatory. On the other hand, galactooligosaccharides obtained from lactose can be used as prebiotic for beneficial microorganisms for the human gastrointestinal tract. All these compounds can be obtained through physicochemical, microbial, or enzymatic treatments. Particularly, enzymatic processes have the advantage of being highly selective, more stable than chemical transformations, and less polluting, making that the global enzyme market grow at accelerated rates. The sources and different products associated with the most used enzymes are particularly highlighted in this review. Moreover, we discuss metagenomics as a tool to identify novel proteolytic enzymes, from both cultivable and uncultivable microorganisms, which are expected to have new interesting activities. Finally enzymes for the transformation of whey sugar are reviewed. In this sense, carbozymes with ß-galactosidase activity are capable of lactose hydrolysis, to obtain free monomers, and transgalactosylation for prebiotics production. KEY POINTS: • Whey can be used to obtain value-added products efficiently through enzymatic treatments • Proteases transform whey proteins into biopeptides with physiological activities • Lactose can be transformed into prebiotic compounds using ß-galactosidases.
Topics: Whey Proteins; Protein Hydrolysates; Prebiotics; Humans; Whey; Lactose; beta-Galactosidase
PubMed: 38819482
DOI: 10.1007/s00253-024-13117-2 -
Nature Communications May 2024Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI)...
Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7 mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.
Topics: Animals; Humans; Male; Mice; Acute Kidney Injury; Autophagy; Autophagy-Related Protein 7; Cisplatin; Disease Models, Animal; Epithelial Cells; Exosomes; Kidney; Kidney Tubules; Macrophages; Mice, Inbred C57BL; MicroRNAs; Mitochondria; Sirtuin 3; Trehalose
PubMed: 38782909
DOI: 10.1038/s41467-024-47842-z -
International Journal of Molecular... Oct 2023Light plays a dominant role in the biosynthesis and accumulation of photosynthetic products. However, the metabolism and translocation of photosynthetic products in...
Light plays a dominant role in the biosynthesis and accumulation of photosynthetic products. However, the metabolism and translocation of photosynthetic products in plants under different light spectra remain elusive. In this study, tomato ( L.) seedlings were treated with different light spectra delivered by light-emitting diodes (LEDs) with the same photosynthetic photon flux density at 300 μmol m s, including monochromatic red (660 nm, R), blue (450 nm, B), sun-like white (W, 380-780 nm), or a combination of R and B lights (R:B = 1:1, RB). Compared with W, the biomass distribution ratio for leaves under R, B, and RB decreased by 5.01-9.53%, while the ratio for stems and roots increased by 3.71-6.92% and 0.14-2.81%, respectively. The photosynthetic carbon distribution expressed as C enrichment was higher in stems and roots under RB and R, while B led to more C transported from leaves and enriched in stems when compared with W. Meanwhile, RB led to significant increases in the activities of phosphate synthase (SPS), sucrose synthase (SS), vacuolar acid invertase (VI), and neutral invertase (NI). The R was more efficient in increasing the activity of SPS and SS, while B was more effective in promoting the activity of VI and NI. The transcript levels of , , , and were upregulated under R, B, and RB. However, the transcript patterns of , , , and were not consistent with the changes in their encoded enzymes, especially the transcript patterns of and . Our study suggests that the red- and blue-light-induced long-distance and short-distance transport of photosynthetic products in plants, respectively, might result from different regulation of sucrose-metabolizing enzymes from transcriptional and post-transcriptional levels.
Topics: Solanum lycopersicum; Seedlings; Carbon; Light; beta-Fructofuranosidase; Sucrose
PubMed: 37894735
DOI: 10.3390/ijms242015054 -
MSphere Aug 2023, , , and are dominant species of the urogenital microbiota. Prior studies suggest that these species play a significant role in the urobiome of healthy females. In...
, , , and are dominant species of the urogenital microbiota. Prior studies suggest that these species play a significant role in the urobiome of healthy females. In our prior genomic analysis of all publicly available and genomes at the time ( = 43), we identified genes unique to these two closely related species. This motivated our further exploration here into their genotypic differences as well as into their phenotypic differences. First, we expanded genome sequence representatives of both species to 61 strains, including publicly available strains and nine new strains sequenced here. Genomic analyses conducted include phylogenetics of the core genome as well as biosynthetic gene cluster analysis and metabolic pathway analyses. Urinary strains of both species were assayed for their ability to utilize four simple carbohydrates. We found that strains can efficiently catabolize maltose, trehalose, and glucose, but not ribose, and strains can utilize maltose and glucose, but not trehalose and ribose. Metabolic pathway analysis clearly shows the lack of within strains, indicative of its inability to catabolize external sources of trehalose. While genotypic and phenotypic observations provide insight into the differences between these two species, we did not find any association with urinary symptom status. Through this genomic and phenotypic investigation, we identify markers that can be leveraged to clearly distinguish these two species in investigations of the female urogenital microbiota. IMPORTANCE We have expanded upon our prior genomic analysis of and strains, including nine new genome sequences. Our bioinformatic analysis finds that and cannot be distinguished by short-read 16S rRNA gene sequencing alone. Thus, to discriminate between these two species, future studies of the female urogenital microbiome should employ metagenomic sequencing and/or sequence species-specific genes, such as those identified here. Our bioinformatic examination also confirmed our prior observations of differences between the two species related to genes associated with carbohydrate utilization, which we tested here. We found that the transport and utilization of trehalose are key distinguishing traits of , which is further supported by our metabolic pathway analysis. In contrast with other urinary species, we did not find strong evidence for either species, nor particular genotypes, to be associated with lower urinary tract symptoms (or the lack thereof).
Topics: Female; Humans; Vagina; RNA, Ribosomal, 16S; Maltose; Lactobacillus; Genotype
PubMed: 37366621
DOI: 10.1128/msphere.00562-22 -
Enzyme and Microbial Technology Sep 2023β-Glucosidases with high catalytic activity and glucose tolerant properties possess promising applications in lignocellulose-based industries. To obtain enzymes...
β-Glucosidases with high catalytic activity and glucose tolerant properties possess promising applications in lignocellulose-based industries. To obtain enzymes possessing these properties, a semi-rational strategy was employed to engineer the glucose-stimulating β-glucosidase Bgl2A for high cellobiose hydrolysis activity. A total of 18 mutants were constructed. A22S, V224D, and A22S/V224D exhibited high specific activities of 272.06, 237.60, and 239.29 U/mg toward cellobiose, which were 2.5- to 2.8-fold of Bgl2A. A22S, V224D, and A22S/V224D exhibited increased k values, which were 2.7- to 3.1-fold of Bgl2A. A22S and V224D maintained glucose-stimulating property, whereas A22S/V224D lost it. Using 150 g/L cellobiose as the substrate, the amount of glucose produced by A22S was the highest, yielding 129.70 g/L glucose after 3 h reaction at 35 °C. The synergistic effects of the engineered enzymes with commercial cellulase on hydrolyzing cellulose were investigated. Supplemented with the commercial cellulase and A22S, the highest glucose amount of 23.30 g/L was yielded from cellulose with hydrolysis rate of 21.02 %. Given its high cellobiose hydrolysis activity and glucose-stimulating properties, A22S can be used as a component of enzyme cocktail to match mesophilic cellulases for efficient cellulose hydrolysis.
Topics: Cellobiose; Hydrolysis; beta-Glucosidase; Glucose; Cellulase; Cellulose
PubMed: 37473697
DOI: 10.1016/j.enzmictec.2023.110289 -
Scientific Reports Jun 2024Floral nectar sugar composition is assumed to reflect the nutritional demands and foraging behaviour of pollinators, but the relative contributions of evolutionary and...
Floral nectar sugar composition is assumed to reflect the nutritional demands and foraging behaviour of pollinators, but the relative contributions of evolutionary and abiotic factors to nectar sugar composition remain largely unknown across the angiosperms. We compiled a comprehensive dataset on nectar sugar composition for 414 insect-pollinated plant species across central Europe, along with phylogeny, paleoclimate, flower morphology, and pollinator dietary demands, to disentangle their relative effects. We found that phylogeny was strongly related with nectar sucrose content, which increased with the phylogenetic age of plant families, but even more strongly with historic global surface temperature. Nectar sugar composition was also defined by floral morphology, though it was not related to our functional measure of pollinator dietary demands. However, specialist pollinators of current plant-pollinator networks predominantly visited plant species with sucrose-rich nectar. Our results suggest that both physiological mechanisms related to plant water balance and evolutionary effects related to paleoclimatic changes have shaped floral nectar sugar composition during the radiation and specialisation of plants and pollinators. As a consequence, the high velocity of current climate change may affect plant-pollinator interaction networks due to a conflicting combination of immediate physiological responses and phylogenetic conservatism.
Topics: Plant Nectar; Pollination; Biological Evolution; Phylogeny; Flowers; Sugars; Animals; Insecta; Sucrose; Europe; Magnoliopsida; Climate Change
PubMed: 38879632
DOI: 10.1038/s41598-024-64755-5 -
Nature Communications Nov 2023Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species...
Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B (Saccharomyces cerevisiae), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO. In addition, a three-species community is constructed with species A' (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A'; G6P then enters species C to promote the metabolic reaction that converts NAD to NADH. The location of species A' and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA'B, CBA', and A'CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.
Topics: NAD; Hydrogen-Ion Concentration; Sucrose
PubMed: 37980410
DOI: 10.1038/s41467-023-43398-6 -
The Journal of Biological Chemistry Aug 2023Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis, is now the third cause of death worldwide, and COVID-19 infection has been...
Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis, is now the third cause of death worldwide, and COVID-19 infection has been reported as an exacerbation factor of them. In this study, we report that the intratracheal administration of the keratan sulfate-based disaccharide L4 mitigates the symptoms of elastase-induced emphysema in a mouse model. To know the molecular mechanisms, we performed a functional analysis of a C-type lectin receptor, langerin, a molecule that binds L4. Using mouse BMDCs (bone marrow-derived dendritic cells) as langerin-expressing cells, we observed the downregulation of IL-6 and TNFa and the upregulation of IL-10 after incubation with L4. We also identified CapG (a macrophage-capping protein) as a possible molecule that binds langerin by immunoprecipitation combined with a mass spectrometry analysis. We identified a portion of the CapG that was localized in the nucleus and binds to the promoter region of IL-6 and the TNFa gene in BMDCs, suggesting that CapG suppresses the gene expression of IL-6 and TNFa as an inhibitory transcriptional factor. To examine the effects of L4 in vivo, we also generated langerin-knockout mice by means of genome editing technology. In an emphysema mouse model, the administration of L4 did not mitigate the symptoms of emphysema as well as the inflammatory state of the lung in the langerin-knockout mice. These data suggest that the anti-inflammatory effect of L4 through the langerin-CapG axis represents a potential therapeutic target for the treatment of emphysema and COPD.
Topics: Animals; Mice; Disaccharides; Disease Models, Animal; Interleukin-6; Keratan Sulfate; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Lectins, C-Type
PubMed: 37454739
DOI: 10.1016/j.jbc.2023.105052