Elevated pulmonary levels of Axin2 in mice exposed to herbicide 2,4-D with or without endotoxin.

2,4-Dichlorophenoxyacetic acid (2,4-D), a member of the phenoxy family of herbicides is commonly used in agriculture for controlling broadleaf weeds but its uncontrolled and incoherent use has been linked to incidences of lung toxicity. The present study aimed to understand the molecular mechanisms behind the 2,4-D alone or in combination with endotoxin (lipopolysaccharide [LPS]) induced pulmonary toxicity. Blood and lung samples were collected from Swiss albino mice (n = 48) following chronic exposure to high (37 mg/kg; 1/10th of LD50 ) and low (18.5 mg/kg; 1/20th of LD50 ) doses of 2,4-D alone or in combination with endotoxin (80 µg/animal). Transcriptome analysis revealed Wnt Canonical signaling as one of the top dysregulated pathways in mice lung following exposure to 2,4-D with and without endotoxin (LPS) co-exposure. Global view of differentially expressed genes showed increased messenger RNA expression of Axin2 by 0.26, 2.58, 3.14, 2.59, and 2.97 folds following exposure to LPS, high dose alone or in combination with LPS and low dose alone or in combination with LPS, respectively. The microarray data were validated using quantitative polymerase chain reaction and immunohistochemistry. Furthermore, the plasma concentration of Axin2 was elevated in the high dose group as revealed by Sandwich ELISA. The data taken together suggest a role of Axin2 to activate the Canonical Wnt signaling pathway in 2,4-D and or endotoxin-induced lung damage in mice.

An open-label randomised pilot trial on safety of wheat variety C273 in patients with adult celiac disease.

BACKGROUND: The only effective treatment for celiac disease (CeD) is gluten free diet (GFD). However, GFD is restrictive and efforts are being made to explore alternative therapies including safer wheat varieties. Wheat variety C273 has been previously identified to have reduced load of intact T-cell stimulatory epitopes via in silico and in vitro analysis. METHODS: Adult patients diagnosed with CeD and recovered on GFD were included in the study. Patients were randomised into two groups in a 2:1 ratio. Patients in group I had graded introduction of C273 wheat in diet, maintained for 24 weeks; in Group II, wheat was restricted with continuation of GFD. Clinical symptoms, serology [anti-tissue transglutaminase (anti-tTG), anti-endomysial antibody (anti-EMA)], circulating inflammatory biomarkers [intestinal fatty-acid binding protein (I-FABP), plasma citrulline, interferon-γ (IFN-γ)] and histology were evaluated periodically. Final evaluation was performed at week 28. RESULTS: A total of 15 patients were enrolled (Group I: n = 10, Group II: n = 5). All patients except two in Group I remained compliant. None of the remaining eight patients in group I developed symptoms. No significant changes in serology (anti-tTG, anti-EMA) and histology were observed between the two groups at 28 weeks (p > 0.05). Significant changes in plasma citrulline(29.87 ± 8.98 versus 36.58 ± 3.09, p = 0.049) and IFN-γ (44.56 ± 9.74 versus 33.50 ± 3.68; p = 0.031) were observed in Group I. CONCLUSION: Consumption of C273 wheat did not result in development of symptoms or evident changes in serology and histology at 28 weeks. However, variations in circulating inflammatory markers were noted. Larger randomised trials are needed to corroborate these findings. CLINICAL TRIALS REGISTRY-INDIA: CTRI/2018/06/014521.

Anticancer potential of dietary vitamin D and ascorbic acid: A review.

Cancers have been the leading cause of death worldwide and poor diet and physical inactivity are major risk factors in cancer-related deaths. Micronutrients such as vitamins and minerals appear to have preventive properties against cancer. One important mechanism by which dietary changes can exert preventive effects on cancer is via the modulation of micronutrient concentrations in target tissues. Many of these micronutrients are available in the form of dietary supplements, and the intake of these supplements is prevalent in various parts of the world. However, in most cases, it is not known which micronutrient (or combination of micronutrients) is best when it comes to lowering the risk of cancer. The present review illustrates the effect of vitamin D and ascorbic acid intake on preventing cancer.