Association of stat6 gene variants with food allergy diagnosed by double-blind placebo-controlled food challenges

Abstract

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analyzed including 262 children (71.0%) with food allergy. Associations were tested by family based association testing (FBAT). The A alleles of both SNPs were associated with food allergy (p=0.036 and p=0.013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all p<0.05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4+ T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.

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Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A

Abstract

Objectives

Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a variety of diseases, including some tumours. However, the effects of GRh2 on prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the present study.

Materials and methods

PC3 and DU145 PC cell lines were exposed to GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation. Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by RT-qPCR. Protein levels were assessed by Western blotting. Bioinformatics and dual luciferase reporter assay were applied to determine the functional binding of miRNA to mRNA of target gene.

Results

GRh2 dose-dependently decreased PC cell proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose-dependently increased the protein, but not mRNA of a cell-cycle suppressor CDKN1A in PC cells, suggesting the presence of microRNA (miRNA)-mediated protein translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3′-UTR of CDKN1A, miR-4295 was specifically found to be suppressed dose-dependently by GRh2 in PC cells. Moreover, miR-4295 bound CDKN1A to suppress its protein translation. Furthermore, cell proliferation in PC cells that overexpressed miR-4295 did not alter in response to GRh2.

Conclusions

GRh2 may inhibit PC cell growth through suppression of microRNA-4295 that activates CDKN1A.

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Pregnancy on vandetanib in metastatic medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2B

Abstract

Vandetanib is a tyrosine kinase inhibitor (TKI) used in the treatment of medullary thyroid carcinoma occurring in >95% of patients with multiple endocrine neoplasia type 2b (MEN 2b). Pregnancy in women with MEN 2b on vandetanib is previously unreported and has multiple potential implications for both the mother and developing fetus [1]. We describe the case of a 22 year old woman with a background of MEN 2b who was first diagnosed aged 6 presenting with marfanoid habitus, and oral mucosal neuromas.

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Glucagon-like peptide 2 decreases osteoclasts by stimulating apoptosis dependent on nitric oxide synthase

Abstract

Objectives

Glucagon-like peptide 2 (GLP2) is involved in the regulation of energy absorption and metabolism. Despite the importance of the GLP2 signalling mechanisms on osteoclast, little has been studied on how GLP2 works during osteoclastogenesis.

Materials and Methods

RAW264.7 cells were infected with rLV-Green-GLP2. The induction of osteoclasts was performed by RANKL. TRAP were detected by RT-PCR, Western blotting and staining. Total nitric oxide and total NOS activity were measured. Cells apoptosis was detected by Hoest33258 and Annix V staining. Animal test, chromatin immunoprecipitation (CHIP), co-immunoprecipitation(IP) and luciferase reporter assay were also performed.

Results

We indicate that GLP2 is associated with osteoporosis-related factors in aged rats, including BALP, TRAP, IL6, TNFα, Nitric Oxide (NO), iNOS, calcitonin and occludin. Moreover, GLP2 is demonstrated to result in negative action during proliferation of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Furthermore, GLP2 decreases osteoclasts induced from monocyte/macrophage cells RAW264.7 as well as the serum TRAP activity in aged rats. Mechanistic investigations reveal GLP2 enhances the expression of iNOS through stimulating the activity of TGFβ-Smad2/3 signalling in osteoclasts. In particular, inhibition of TGFβ fully abrogates this function of GLP2 in osteoclasts. Strikingly, overexpression of GLP2 significantly increases the product of nitric oxide via iNOS which promotes apoptosis of osteoclasts by decreasing bcl2 or increasing caspase3. Thereby, the ability of GLP2 to regulate apoptosis depends on TGFβ-Smad2/3-iNOS-NO signalling pathway since total NOS inhibitor L-NMMA specifically inhibits the actions by GLP2.

Conclusions

GLP2 induces apoptosis via TGFβ-Smad2/3 signalling, which contributes to the inhibition of the proliferation of osteoclasts and which may provide potential therapeutic targets for the treatment of osteoporosis.

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Evaluation and application of prebiotic and probiotic ingredients for development of ready to drink tea beverage

Abstract

Ready-to-drink (RTD) ice tea is a ready prepared tea, produced from green and black tea originating from same plant Camellia sinensis. The objective of this study was to determine the effect of prebiotics [galacto-oligosaccharide (GOS), fructo-oligosaccharide (FOS), and inulin] or synbiotic ingredients (GOS, FOS, inulin, and Lactobacillus acidophilus) on the sensory properties and consumer acceptability of RTD. The quality of green tea extract (GTE) and black tea extract (BTE) was improved with pretreatment of cellulase and pectinase enzymes. The combined enzymatic extraction amplified total extractives up to 76% in GTE and 72% in BTE. Total polyphenol was found to be enhanced to 24% in GTE and 19% in BTE. GTE was further selected for development of RTD in two different formats; synbiotic RTD and prebiotic RTD premix and analyzed for sensory attributes (colour, aroma, taste, and acceptability). Synbiotic RTD was also evaluated for stability over a period of 28 days at 4 °C. Synbiotic RTD developed an unpleasant flavor and aroma during the shelf life. Premix format of RTD developed using spray drying was reconstituted and found to be functionally and sensorially acceptable.

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IJMS, Vol. 19, Pages 611: The Role of the Estrogen Pathway in the Tumor Microenvironment

IJMS, Vol. 19, Pages 611: The Role of the Estrogen Pathway in the Tumor Microenvironment

International Journal of Molecular Sciences doi: 10.3390/ijms19020611

Authors: Natalie Rothenberger Ashwin Somasundaram Laura P. Stabile

Estrogen receptors are broadly expressed in many cell types involved in the innate and adaptive immune responses, and differentially regulate the production of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms of estrogen signaling are well characterized in multiple carcinomas including breast, ovarian, and lung, recent investigations have identified a potential immune regulatory role of estrogens in the tumor microenvironment. Tumor immune tolerance is a well-established mediator of oncogenesis, with increasing evidence indicating the importance of the immune response in tumor progression. Immune-based therapies such as antibodies that block checkpoint signals have emerged as exciting therapeutic approaches for cancer treatment, offering durable remissions and prolonged survival. However, only a subset of patients demonstrate clinical response to these agents, prompting efforts to elucidate additional immunosuppressive mechanisms within the tumor microenvironment. Evidence drawn from multiple cancer types, including carcinomas traditionally classified as non-immunogenic, implicate estrogen as a potential mediator of immunosuppression through modulation of protumor responses independent of direct activity on tumor cells. Herein, we review the interplay between estrogen and the tumor microenvironment and the clinical implications of endocrine therapy as a novel treatment strategy within immuno-oncology.

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Our cities are driving evolution and it’s not all bad news

Urbanisation may be overrunning our planet, but in his book Darwin Comes to Town, evolutionary biologist Menno Schilthuizen seeks – and finds – the positives

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