BAFF selectively enhances the survival of plasmablasts generated from human memory B cells

The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors — transmembrane activator of and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R). To elucidate the contribution of BAFF to the differentiation of B cells into ISCs, we tracked the fate of human memory B cells stimulated with BAFF or CD40L. BAFF and CD40L significantly increased the overall number of surviving B cells. This was achieved via distinct mechanisms. CD40L induced proliferation of nondifferentiated blasts, while BAFF prevented apoptosis of ISCs without enhancing proliferation. The altered responsiveness of activated memory B cells to CD40L and BAFF correlated with changes in surface phenotype such that expression of CD40 and BAFF-R were reduced on ISCs while BCMA was induced. These results suggest BAFF may enhance humoral immunity in vivo by promoting survival of ISCs via a BCMA-dependent mechanism. These findings have wide-ranging implications for the treatment of human immunodeficiencies as well as autoimmune diseases.This work was supported by the National Health and Medical Research Council of Australia. S.G. Tangye was supported by a U2000 Postdoctoral Fellowship awarded by the University of Sydney. P.D. Hodgkin is a Senior Research Fellow of the National Health and Medical Research Council of Australia. F. Mackay is a Wellcome Trust Senior Research Fellow

Bone Marrow B cell Precursor Number after Allogeneic Stem Cell Transplantation and GVHD Development

Patients without chronic graft-versus-host disease (cGVHD) have robust B cell reconstitution and are able to maintain B cell homeostasis after allogeneic hematopoietic stem cell transplantation (HSCT). To determine whether B lymphopoiesis differs before cGVHD develops, we examined bone marrow (BM) biopsies for terminal deoxynucleotidyl transferase (TdT) and PAX5 immunostaining early post-HSCTat day 30 when all patients have been shown to have high B cell activating factor (BAFF) levels. We found significantly greater numbers of BM B cell precursors in patients who did not develop cGVHD compared with those who developed cGVHD (median = 44 vs 2 cells/high powered field [hpf]; respectively; P < .001). Importantly, a significant increase in precursor B cells was maintained when patients receiving high-dose steroid therapy were excluded (median = 49 vs 20 cells/hpf; P =.017). Thus, we demonstrate the association of BM B cell production capacity in human GVHD development. Increased BM precursor B cell number may serve to predict good clinical outcome after HSCT

Development and Validation of the Vietnamese Children’s Short Dietary Questionnaire to Evaluate Food Groups Intakes and Dietary Practices among 9–11-Year-Olds Children in Urban Vietnam

This study aims to develop and assess the reproducibility and validity of the Vietnamese Children’s Short Dietary Questionnaire (VCSDQ) in evaluating food groups intakes and dietary practices among school-aged children 9–11 years old in urban Vietnam. A 26-item questionnaire covering frequency intakes of five core food groups, five non-core food groups, five dietary practices over a week, and daily intakes of fruits, vegetables, and water was developed. Children (n = 144) from four primary schools in four areas of Ho Chi Minh City, Vietnam completed the VCSDQ twice, as well as three consecutive 24 h recalls over a week. Intra-class correlation, Spearman correlation, weighted kappa, cross-classification, and Bland–Altman plots were used to evaluate the reproducibility and validity. The direct validity of food groups from VCSDQ against the 24 h recalls was examined using Wilcoxon-test for trend. The VCSDQ had good reproducibility in 12 out of 15 group items; the ICC ranged from 0.33 (grains) to 0.84 (eating while watching screens). This VCSDQ had low relative validity, two items (instant noodles, eating while watching screens) had a moderate to good agreement (k = 0.43, k = 0.84). There was good direct validity in three core-food groups (fruits, vegetables, dairy) and three non-core food groups (sweetened beverages, instant noodles, processed meat). In addition, the VCSDQ can also be used to classify daily intakes of fruits and vegetables from low to high.</p

Dietary patterns and child, parental, and societal factors associated with being overweight and obesity in Vietnamese children living in Ho Chi Minh city

Abstract Childhood overweight and obesity are rapidly increasing in urban Vietnam. Dietary patterns are understudied for their association with obesity risk in these children, and it is unclear which parental and societal factors should be targeted in prevention efforts. The study assessed child characteristics, dietary patterns, parental and societal factors for associations with childhood overweight and obesity status in Ho Chi Minh City, Vietnam. A sample of 221 children aged 9–11 years was randomly selected from four Ho Chi Minh City primary schools. Weight, height and waist circumference were measured using standardized methods. Three 24‐h dietary recalls were collected from 124 children, which were used to assess dietary patterns using principal component analysis (PCA). Parents completed a questionnaire about child, parental and societal factors. The overall prevalence of obesity was 31.7% and of combined overweight and obesity 59.3%. Three main dietary patterns from 10 food groups were identified by PCA: traditional (grains, vegetables, meat and meat alternatives), discretionary (snacks and sweetened beverages), and industrialized (fast food and processed meat). Children with higher discretionary diet scores had higher odds of being overweight. Being a boy, screen time over 2 h/day, parental underestimation of child weight status, father's obesity, and household income in the lowest quintile were positively associated with childhood obesity. Future intervention programmes in Vietnam need to consider targeting children's unhealthy diets and parental perceptions of child weight status, as well as focusing on upstream approaches that reduce inequities contributing to childhood obesity and concomitant dietary patterns

The search for novel treatment agents for pancreatic cancer : tales from the land and sea

Background: Pancreatic cancer (PC) is a disastrous disease with a dismal survival rate of only 5%. The current standard of care for PC patients consists of surgery and/or treatment with gemcitabine, a natural product‐derived chemotherapeutic which has been shown to have a modest effect for some patients, however it is not a long‐term curative treatment and results in many unwanted side effects. Natural therapies have the advantage of being relatively inexpensive to manufacture and are usually very tolerable and effective. Therefore, there is a strong need for novel, naturally occurring therapeutic options for PC. Aim: To determine if crude extracts and/or purified compounds from various Australian and South East Asian flora and fauna (Vietnamese medicinal plants, Blueberry ash, bitter melon, Eucalyptus and marine invertebrates) exert anti‐cancer activity in vitro, with an emphasis on pancreatic cancer. Methods: Pancreatic cancer cell lines (BxPC3, MiaPaCa2 and CFPAC‐1) and normal human pancreatic epithelial cells (HPDE) were treated with varying doses of crude extracts and purified compounds over a range of treatment times. Cell viability was assessed using CCK8 and MTT viability assays to determine the extent of anti‐cancer activity due to growth inhibition and/or apoptosis. Results: Significant growth inhibition of pancreatic cancer cells was observed with the purified compound pristimerin (from 2 Vietnamese medicinal plants), which displayed an IC50 of 25 μg/mL for HPDE cells. Conclusions: Purified compounds and crude extracts from plants and marine invertebrates show significant selective pancreatic cancer growth inhibition in vitro at concentrations with minimal effect on normal pancreatic cells, therefore showing promise as novel anti‐pancreatic cancer therapies