Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response

Glucosamine, a natural glucose derivative and an essential component of glycoproteins and proteoglycans, has been safely used to relieve osteoarthritis in humans. Recent studies have shown that glucosamine also possesses immunosuppressive properties and is effective in prolonging graft survival in mice. Whether this reagent is effective in human multiple sclerosis (MS), an inflammatory demyelination in the CNS, is not known. We thus investigated the therapeutic effect of glucosamine on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We demonstrated that oral, i.p., or i.v. administration of glucosamine significantly suppressed acute EAE, with reduced CNS inflammation and demyelination. A significant, albeit not strong, blockade of Th1 response and an up-regulation of Th2 cytokines (IL-5 and IL-10) are observed in the splenocytes of glucosamine-treated mice. Glucosamine also regulates IL-5 and IL-10 in vitro. As glucosamine is able to effectively suppress acute EAE, has low or absent toxicity, and has been safely used in humans orally, our study suggests a potential use for this drug alone or in combination with other disease-modifying immunotherapies to enhance their efficacy and reduce their doses in MS and possibly other autoimmune disorders. Furthermore, because glucosamine functions not simply as an immunosuppressant, but as a mild immunomodulator, administration of glucosamine provides a novel immunoregulatory approach for autoimmune disorders.     

Hydrogen sulfide concentrations in indoor air of thermal springs

This study aimed to assess hydrogen sulfide (H₂S) concentrations in the pool indoor air of hot springs and its link to some physicochemical properties of the springs in Ardabil province. Twenty-two hot springs from different regions were selected and monitored for H₂S concentrations using a portable gas meter. Respective mean concentrations of H₂S in hot springs indoor air were 9.11 ± 11. Ghotour Souei hot springs had the highest concentration of H₂S with a mean concentration of 29.4 ± 7.7 and 25.2 ± 8.16 ppm at the source and general pool areas, respectively. Oxidation-reduction potential and pH of the water were the most important factor influencing H₂S concentrations in the hot springs. H₂S concentrations in indoor air of Ardabil hot springs were noticeably higher than OEL-TWA and OEL-STEL, and therefore may pose important risks for human health on both short-and long-term exposures.     

Neuritogenic Lewis rat T cells use Tcrb chains that include a new Tcrb-V8 family member

The P2 protein obtained from Schwann cells induces a population of T cells which, upon adoptive transfer, causes the disease experimental allergic neuritis (EAN), an animal model for Guillain-Barre syndrome. In this report, a truncated peptide, FR22, derived from a previously reported neuritogenic T-cell determinant, was used to generate from Lewis rats T cells that were shown to cause EAN. Since our previous studies showed that Tcrb-V8 was used by a majority of T-cell hybridomas specific for the neuritogenic peptide P26, which contains the FR22 sequence, we sequenced the Tcrb-V8 ⁺ mRNA from FR22-specific T-cell lines, and compared the sequences obtained with those obtained from similarly generated myelin basic protein (MBP) 68–88-specific Lewis rat T-cell lines. We found that in the EAN lines, several members of the Tcrb-V8 family were used, including a new family member, Tcrb-V8E. This was more diverse than the MBP-68–88-specific response in which only a single Tcrb-V8 family member was used. Also, in the EAN lines, the beta chain sequences did not show the same conserved junctional regions seen in the MBP lines. Thus, T-cell receptor beta chain usage in the response to this dominant neuritogenic peptide appears to be less restricted than the response to the dominant encephalitogenic determinant of MBP both in V region usage and in CDR3 usage.The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence databse and have been assigned the accession numbers UO6100 (Tcrb-V8A), UO6101 (Tcrb-V8B), UO6102 (Tcrb-V8C), UO6103 (Tcrb-V8D), and UO6104 (Tcrb-V8E)     

Effect of glucose ingestion on the metabolism of free fatty acids in human subjects

The rate of appearance of (14)CO(2) in expired air after the injection of a single dose of NaH(14)CO(3) has been determined in normal individuals both in the fasted and fed states. These data were combined with previously obtained results on the rate of disappearance of injected palmitate-(14)C from the bloodstream, to give a multicompartmental analysis of free fatty acid oxidation and esterification. The results confirm that glucose feeding promptly inhibits the rate of free fatty acid oxidation to CO(2). The "irreversible disposal rate," or irreversible flux of free fatty acids from the plasma, was also consistently reduced by glucose feeding. The diminution in irreversible disposal, not accounted for entirely by reduction of direct oxidation, must indicate suppression of other disposal mechanisms, including net esterification of free fatty acids. An average drop of 49% in "net esterification" when glucose was given may be compared with the 65% inhibition of rapid free fatty acid oxidation.     

N–H bond cleavage of ammonia on graphene-like B36 borophene: DFT studies

The prediction of domain/linker residues in protein sequences is a crucial task in the functional classification of proteins, homology-based protein structure prediction, and high-throughput structural genomics. In this work, a novel consensus-based machine-learning technique was applied for residue-level prediction of the domain/linker annotations in protein sequences using ordered/disordered regions along protein chains and a set of physicochemical properties. Six different classifiers—decision tree, Gaussian naïve Bayes, linear discriminant analysis, support vector machine, random forest, and multilayer perceptron—were exhaustively explored for the residue-level prediction of domain/linker regions. The protein sequences from the curated CATH database were used for training and cross-validation experiments. Test results obtained by applying the developed PDP-CON tool to the mutually exclusive, independent proteins of the CASP-8, CASP-9, and CASP-10 databases are reported. An n-star quality consensus approach was used to combine the results yielded by different classifiers. The average PDP-CON accuracy and F-measure values for the CASP targets were found to be 0.86 and 0.91, respectively. The dataset, source code, and all supplementary materials for this work are available at https://cmaterju.org/cmaterbioinfo/ for noncommercial use.

     

The Role of Historical Persian Gardens on the Health Status of Contemporary Urban Residents

The inherent economic and social challenges in major cities have been known to foster stress among the urban population. Frequent stress over long periods may well have serious damaging outcomes, resulting in ailments such as burnout syndrome, sleeplessness and exhaustion, depression, feelings of panic, among others. Therefore, providing access to resources that may enable people to cope with the stress of urban life has become a crucial phenomenon in the twentieth century. Increasing empirical evidence indicates that the presence of natural areas can contribute to enhancing the quality of life in many ways. This study examines two historical Persian gardens from the residents’ perspective in well-known, historic cities of Iran: Isfahan and Kerman. The data were collected through questionnaires (n = 252), semi-structured interviews (n = 20), and visual observation techniques. The findings demonstrate that nature, diversity and the gardens’ historical background, and coherence motivate the residents’ frequent visits to the gardens, which help to address their social, psychological, and physical needs. In addition, the residents’ involvements and the variety of experiences that occur in the gardens lead to the creation of deeper meanings and values associated with the gardens. Subsequently, these construct functional and emotional attachment that evokes a sense of place and identity and may contribute to society’s health and well-being.     

Interaction of papaverine with the enalapril-induced cough in guinea pig

BACKGROUND: Angiotensin Converting Enzyme Inhibitors (ACEIs) like enalapril are extremely effective in the treatment of hypertension and heart failure. One of the most important side-effects of these drugs which can lead to cessation of therapy is a persistant dry cough, induced because of increased bradykinin levels in the lung. Although antitussive alkaloids like codeine are effective in suppressing this cough, they too present a wide range of side-effects, most notably addiction. OBJECTIVE: In a previous work we were able to show that noscapine, a non-narcotic antitussive agent, was able to decrease enalapril induced cough in guinea pigs. In this work, papaverine, another non-narcotic alkaloid found in opium latex was tested in the guinea pig model for antitussive activity. METHOD: Cough was induced in enalapril pretreated guinea pigs by forcing the animals to inspire capsaicin aerosol in an air-tight chamber. Coughs were recorded in control animals and in those which had received different doses of papaverine. Characteristic changes in chamber air pressure, were detected by a pressure transducer. RESULTS:. At low doses (0.5 and 0.25 mg/kg) papaverine was able to decrease enalapril induced cough. CONCLUSION. This effect was not mediated by the action of the drug on mu receptors and was only observed in animals treated with enalapril.     

Dendritic cells transduced with SOCS-3 exhibit a tolerogenic/DC2 phenotype that directs type 2 Th cell differentiation in vitro and in vivo

Dendritic cells (DCs) have been suggested to direct a type of Th differentiation through their cytokine profile, e.g., high IL-12/IL-23 for Th1 (named DC1/immunogenic DCs) and IL-10 for Th2 (DC2/tolerogenic DCs). Suppressor of cytokine signaling (SOCS)-3 is a potent inhibitor of Stat3 and Stat4 transduction pathways for IL-23 and IL-12, respectively. We thus hypothesize that an enhanced SOCS-3 expression in DCs may block the autocrine response of IL-12/IL-23 in these cells, causing them to become a DC2-type phenotype that will subsequently promote Th2 polarization of naive T cells. Indeed, in the present study we found that bone marrow-derived DCs transduced with SOCS-3 significantly inhibited IL-12-induced activation of Stat4 and IL-23-induced activation of Stat3. These SOCS-3-transduced DCs expressed a low level of MHC class II and CD86 on their surface, produced a high level of IL-10 but low levels of IL-12 and IFN-gamma, and expressed a low level of IL-23 p19 mRNA. Functionally, SOCS-3-transduced DCs drove naive myelin oligodendrocyte glycoprotein-specific T cells to a strong Th2 differentiation in vitro and in vivo. Injection of SOCS-3-transduced DCs significantly suppressed experimental autoimmune encephalomyelitis, a Th1 cell-mediated autoimmune disorder of the CNS and an animal model of multiple sclerosis. These results indicate that transduction of SOCS-3 in DCs is an effective approach to generating tolerogenic/DC2 cells that then skew immune response toward Th2, thus possessing therapeutic potential in Th1-dominant autoimmune disorders such as multiple sclerosis.     

Loss of the surface antigen 3G11 characterizes a distinct population of anergic/regulatory T cells in experimental autoimmune encephalomyelitis

T cell anergy is an important mechanism in the induction of peripheral tolerance against autoimmune diseases, yet no surface marker unique to anergic T cells in these diseases has been identified. In this study we induced in vivo anergy by i.v. tolerance against experimental autoimmune encephalomyelitis in myelin basic protein TCR transgenic mice, and showed that the hyporesponsiveness of autoantigen-reactive T cells from tolerized mice was associated with a dramatic loss of 3G11, a cell surface molecule on the surface of CD4+ T cells. Purified 3G11-CD4+ T cells lost autoantigen-induced proliferation and IL-2 production, whereas 3G11+CD4+ T cells retained responsiveness. Furthermore, 3G11- T cells actively suppressed proliferation and Th1 cytokine production of 3G11+ T cells and splenocytes of nontolerized mice. Active suppression by 3G11- T cells was at least partially due to soluble immunoregulatory factors, including IL-10. The T regulatory property of 3G11- T cells was confirmed in vivo because the transfer of purified 3G11- T cells effectively suppressed clinical experimental autoimmune encephalomyelitis. We conclude that loss of the surface molecule 3G11 characterizes a distinct population of anergic/regulatory T cells. This is the first demonstration of the ability to identify and purify anergic T cells by a distinct cell surface marker in an autoimmune disease and paves the way for a better understanding of the mechanism of tolerance in autoimmune diseases.