Age-mediated gut microbiota dysbiosis promotes the loss of dendritic cells tolerance

The old age-related loss of immune tolerance inflicts a person with a wide range of autoimmune and inflammatory diseases. Dendritic cells (DCs) are the sentinels of the immune system that maintain immune tolerance through cytokines and regulatory T-cells generation. Aging disturbs the microbial composition of the gut, causing immune system dysregulation. However, the vis-à-vis role of gut dysbiosis on DCs tolerance remains highly elusive. Consequently, we studied the influence of aging on gut dysbiosis and its impact on the loss of DC tolerance. We show that DCs generated from either the aged (DC^Old) or gut-dysbiotic young (DC^Dysbiotic) but not young (DC^Young) mice exhibited loss of tolerance, as evidenced by their failure to optimally induce the generation of Tregs and control the overactivation of CD4⁺ T cells. The mechanism deciphered for the loss of DC^Old and DC^Dysbiotic tolerance was chiefly through the overactivation of NF-κB, impaired frequency of Tregs, upregulation in the level of pro-inflammatory molecules (IL-6, IL-1β, TNF-α, IL-12, IFN-γ), and decline in the anti-inflammatory moieties (IL-10, TGF-β, IL-4, IDO, arginase, NO, IRF-4, IRF-8, PDL1, BTLA4, ALDH2). Importantly, a significant decline in the frequency of the Lactobacillus genus was noticed in the gut. Replenishing the gut of old mice with the Lactobacillus plantarum reinvigorated the tolerogenic function of DCs through the rewiring of inflammatory and metabolic pathways. Thus, for the first time, we demonstrate the impact of age-related gut dysbiosis on the loss of DC tolerance. This finding may open avenues for therapeutic intervention for treating age-associated disorders with the Lactobacillus plantarum.     

Silicon and Nitric Oxide-Mediated Regulation of Growth Attributes,Metabolites and Antioxidant Defense System of Radish (<i>Raphanus sativus</i> L.) under Arsenic Stress

Arsenic (As) contaminated food chains have emerged as a serious public concern for humans and animals and are known to affect the cultivation of edible crops throughout the world. Therefore, the present study was designed to investigate the individual as well as the combined effects of exogenous silicon (Si) and sodium nitroprusside (SNP), a nitric oxide (NO) donor, on plant growth, metabolites, and antioxidant defense systems of radish (Raphanus sativus L.) plants under three different concentrations of As stress, i.e., 0.3, 0.5, and 0.7 mM in a pot experiment. The results showed that As stress reduced the growth parameters of radish plants by increasing the level of oxidative stress markers, i.e., malondialdehyde and hydrogen peroxide. However, foliar application of Si (2 mM) and pretreatment with SNP (100 µM) alone as well as in combination with Si improved the plant growth parameters, i.e., root length, fresh and dry weight of plants under As stress. Furthermore, As stress also reduced protein, and metabolites contents (flavonoids, phenolic and anthocyanin). Activities of antioxidative enzymes such as catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (POD), and polyphenol oxidase (PPO), as well as the content of non-enzymatic antioxidants (glutathione and ascorbic acid) decreased under As stress. In most of the parameters in radish, As III concentration showed maximum reduction, as compared to As I and II concentrations. However, the individual and combined application of Si and NO significantly alleviated the As-mediated oxidative stress in radish plants by increasing the protein, and metabolites content. Enhancement in the activities of CAT, APX, POD and PPO enzymes were recorded. Contents of glutathione and ascorbic acid were also enhanced in response to co-application of Si and NO under As stress. Results obtained were more pronounced when Si and NO were applied in combination under As stress, as compared to their individual application. In short, the current study highlights that Si and NO synergistically regulate plant growth through lowering the As-mediated oxidative stress by upregulating the metabolites content, activity of antioxidative enzymes and non-enzymatic antioxidants in radish plants.

     

Effect of hypocholesterolemic agents of plant origin on catecholamine biosynthesis in normal and cholesterol fed rabbits

The effect of lipid lowering agents of plant origin garlic oil and guggulipid on the levels of catecholamine and dopamine Β-hydroxylase activity of normal and cholesterol fed rabbit tissues has been studied. The catecholamine levels and enzyme activity were found to be decreased in cholesterol (500 mg/kg body wt) fed animals. The feeding of garlic oil (5 mg/kg body wt) and guggulipid (100 mg/kg body wt) an exudate ofCommiphora mukul, to normal rabbits caused significant increase in the dopamine-Β-hydroxylase activity and catecholamine levels, while the feed helped the hypercholesterolemic rabbits to recover the decrease in catecholamine biosynthesis C.D.R.I. Communication No. 3435.     

Bovine aortic chondroitin sulphate- and dermatan sulphate-containing proteoglycans. Isolation, fractionation and chemical characterization.

1. Guanidinium chloride (4M) in the presence of proteinase inhibitors extracted 90% of bovine aorta galactosaminoglycans as proteoglycans that were subsequently purified by ion-exchange and gel chromatography. 2. Fractionation of the calcium salts of the purified proteoglycans with increasing concentration of ethanol yielded fractions PG-25 (28%), PG-35 (45%) and PG-50 (37%). 3. Fraction PG-50 contained proteochondroitin 6-sulphate, whereas fractions PG-25 and PG-35 were proteodermatan sulphates of greatly different carbohydrate composition; the molar proportions of L-iduronate-N-acetylgalactosamine 4-sulphate, D-glucuronate-N-acetyl-galactosamine 4-sulphate and D-glucuronate-N-acetylgalactosamine 6-sulphate were 75: 18 :7 in fraction PG-25 and 14 :46 :40 in fraction PG-35. 4. The presence of alternating or mixed sequences with L-iduronate- and D-glucuronate-containing repeating disaccharides was indicated by the formation of tetrasaccharides after chondroitinase AC digestion (single L-iduronate residues) and by the release of fragments containing four or five consecutive D-glucuronate-N-acetylgalactosamine repeats after periodate oxidation and alkaline elimination. 5. The amino acid compositions of fractions PG-25 and PG-35 were similar and markedly different from that of fraction PG-50, which also contained more side chains.     

A single mutation affects L-serine deaminase, L-leucyl-, L-phenylalanyl-tRNA protein transferase, and proline oxidase activity in Escherichia coli K-12.

A mutation at a single locus, wyb, results in several phenotypic changes in Escherichia coli K-12. The Wyb- phenotype includes: (i) an increase in L-serine deaminase activity, together with a loss of inducibility by L-leucine; (ii) an absence of L-leucyl-, L-phenylalanyl-tRNA protein transferase activity; (iii) inducibility of proline oxidase by proline; and (iv) a loss of ability to use maltose as a carbon and energy source.     

Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, the active principle from Picrorhiza kurrooa, at a dose of 6 mg/kg, po for two weeks showed significant protection against changes in liver and brain glutathione metabolism of Plasmodium berghei infected Mastomys natalensis. The depletion of reduced glutathione level and inhibition of glutathione-S-transferase, glutathione reductase and glutathione peroxidase activities due to P. berghei infection were markedly recovered by picroliv. The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism.     

Development of thermotolerance in Neurospora crassa by heat shock and other stresses eliciting peroxidase induction.

Hyperthermia, CdCl2, sodium arsenite, and H2O2 led to the rapid appearance of high levels of peroxidase in Neurospora crassa cultures and induced tolerance toward normally lethal temperatures in 60-h-old colonies. Intracellular superoxide dismutase levels did not correlate with the development of thermotolerance.