Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function

Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation of THP-1 cells with ligands of plasma membrane associated TLRs 2 and 4, endosomal TLRs 7 and 8 as well as stem cell growth factor (SCF). Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) transcription complexes were found to be responsible for XOD upregulation. Importantly, the mammalian target of rapamycin (mTOR), a major myeloid cell translation regulator, was also found to be essential for XOD activation. Specific inhibition of XOD by allopurinol and sodium tungstate led to an increase in intracellular AMP levels triggering downregulation of mTOR activation by phosphorylation of its T2446 residue. Taken together, our results demonstrate for the first time that XOD is not only activated by pro-inflammatory stimuli or SCF but also plays an important role in maintaining mTOR-dependent translational control during the biological responses of human myeloid cells

Study on nutritional status of children under 5 years in palpa district, nepal: speacial reference to baal vita

Background: Malnutrition is a pathological state resulting from a relative or absolute deficiency or excess of one or more essential nutrients. Malnutrition is a major underlying cause of the child morbidity and mortality in Nepal. Adequate nutrition is a fundamental right for every human being. Malnourished child is depriving from physical and mental development. Objectives: To assess the nutritional status of children under 5 years and to find out the knowledge and practice regarding micronutrient powder “Baal vita” Materials and Methods: Descriptive cross sectional community based study was conducted in Palpa district, total of 390 respondents at the age of 6-59 months were selected with the help of multistage sampling. Through anthropometry, prevalence of underweight, stunting and wasting was determined. Results: Prevalence of underweight, stunting and wasting was 25.9%, 27.2% and 7.3% respectively. The association between age of the mother at the birth of the children and nutritional status of children is not statistically significant. Majority of the children (80.5%) used to take junk foods sometimes, followed by 16.7% very often, 2.8% children never used to take. Majority of the children (52.6%) were taken the micronutrient powder (first course) but the coverage of second course of micronutrient powder was 29.5% and followed by third course coverage was only 18.9%. Conclusion: The nutritional status of children in this study were found to be satisfactory because compared to the Millennium Development Goals (MDGs) target but the coverage of micronutrient powder is low

NATURAL PRODUCTS AS AN IMPORTANT LEADS FOR DISCOVERY OF NEW ANTITUBERCULAR AGENTS: A REVIEW

There is a very much need for a discovery of new molecules a potent molecule that can cure tuberculosis and prevent the recurrence. A multidisciplinary approach is required to procure a potent bioactive compound and this includes expertise in the fields of ethnobotany, ethnopharmacology and Phytochemistry. The present communication acts as a bioprospecting source for the drug discovery against tuberculosis, including several anti tubercular agents which is used by used by tribal people and prescribed by THPS which showed a good inhibition rate. Therefore, this review strives to describe the literature on the traditional plants/potent molecules those have been proved to have antimicrobial activity and to provide essential discussion and accelerate the research.Â

T lymphocytes induce human cancer cells derived from solid malignant tumors to secrete galectin-9 which facilitates immunosuppression in cooperation with other immune checkpoint proteins.

BACKGROUND Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. However, solid tumor cells at rest are known to secrete either very low amounts of galectin-9 or, in most of the cases, do not secrete it at all. Our aims were to elucidate whether T cells can induce galectin-9 secretion in human cancer cells derived from solid malignant tumors and whether this soluble form displays higher systemic immunosuppressive activity compared with the cell surface-based protein. METHODS A wide range of human cancer cell lines derived from solid tumours, keratinocytes and primary embryonic cells were employed, together with helper and cytotoxic T cell lines and human as well as mouse primary T cells. Western blot analysis, ELISA, quantitative reverse transcriptase-PCR, on-cell Western and other measurement techniques were used to conduct the study. Results were validated using in vivo mouse model. RESULTS We discovered that T lymphocytes induce galectin-9 secretion in various types of human cancer cells derived from solid malignant tumors. This was demonstrated to occur via two differential mechanisms: first by translocation of galectin-9 onto the cell surface followed by its proteolytic shedding and second due to autophagy followed by lysosomal secretion. For both mechanisms a protein carrier/trafficker was required, since galectin-9 lacks a secretion sequence. Secreted galectin-9 pre-opsonised T cells and, following interaction with other immune checkpoint proteins, their activity was completely attenuated. As an example, we studied the cooperation of galectin-9 and V-domain Ig-containing suppressor of T cell activation (VISTA) proteins in human cancer cells. CONCLUSION Our results underline a crucial role of galectin-9 in anticancer immune evasion. As such, galectin-9 and regulatory pathways controlling its production should be considered as key targets for immunotherapy in a large number of cancers

What makes you not a Sikh? : a preliminary mapping of values

This study sets out to establish which Sikh values contrasted with or were shared by non-Sikh adolescents. A survey of attitude toward a variety of Sikh values was fielded in a sample of 364 non-Sikh schoolchildren aged between 13 and 15 in London. Values where attitudes were least positive concerned Sikh duties/code of conduct, festivals, rituals, prayer Gurdwara attendance, listening to scripture recitation, the amrit initiation. Sikh values empathized with by non-Sikhs concerned family pride, charity, easy access to ordination and Gurdwaras, maintaining the five Ks, seeing God in all things, abstaining from meat and alcohol and belief in the stories of Guru Nanak. Further significant differences of attitude toward Sikhism were found in comparisons by sex, age and religious affiliation. Findings are applied to teaching Sikhism to pupils of no faith adherence. The study recommends the extension of values mapping to specifically Sikh populations

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation

BACKGROUND: Epicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT’s immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients. METHODS: We recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients’ clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups. RESULTS: Flow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls. CONCLUSION: Adaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile. FUNDING: Barts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419