Bread wheat with enhanced grain carotenoid content: a novel option for wheat biofortification.

Colored wheat has piqued the interest of breeders and consumers alike. The chromosomal segment from 7E of Thinopyrum ponticum, which carries a leaf rust resistant gene, Lr19, has been rarely employed in wheat breeding operations due to its association with the Y gene, which gives a yellow tint to the flour. By prioritizing nutritional content over color preferences, consumer acceptance has undergone a paradigm change. Through marker-assisted backcross breeding, we introduced an alien segment harboring the Y (PsyE1) gene into a high yielding commercial bread wheat (HD 2967) background to generate rust resistant carotenoid biofortified bread wheat. Agro-morphological characterization was also performed on a subset of developed 70 lines having enhanced grain carotene content. In the introgression lines, carotenoid profiling using HPLC analysis demonstrated a considerable increase in ß-carotene levels (up to 12 ppm). Thus, the developed germplasm caters the threat to nutritional security and can be utilized to produce carotenoid fortified wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01338-0.

Elucidation of underlying molecular mechanism of 5-Fluorouracil chemoresistance and its restoration using fish oil in experimental colon carcinoma.

Latest strategies for cancer treatment primarily focus on the use of chemosensitizers to enhance therapeutic outcome. N-3 PUFAs have emerged as the strongest candidate for the prevention of colorectal cancer (CRC). Our previous studies have demonstrated that fish oil (FO) rich in n-3 PUFAs not only increased therapeutic potential of 5-Fluorouracil(5-FU) in colon cancer but also ameliorated its toxicity. Henceforth, the present study is designed to elucidate mechanistic insights of FO as a chemosensitizer to circumvent drug resistance in experimental colon carcinoma. The colon cancer was induced by 1,2-dimethylhydrazine(DMH)/dextran sulfate sodium(DSS) in male Balb/c mice and these animals were treated with 5-FU(12.5 mg/kg b.w.), FO(0.2 ml), or 5-FU + FO(12.5 mg/kg b.w + 0.2 ml) orally for 14 days. The molecular mechanism of overcoming 5-FU resistance using FO in colon cancer was delineated by estimating expression of cancer stem cell markers using flowcytometric method and drug transporters by immunohistochemistry and immunoblotting. Additionally, distribution profile of 5-FU and its cytotoxic metabolite, 5-FdUMP at target(colon), and non-target sites (serum, kidney, liver, spleen) was assessed using high-performance liquid chromatography(HPLC) method. The observations revealed that expression of CSCs markers was remarkably reduced after using fish oil along with 5-FU in carcinogen-treated animals. Interestingly, the use of FO alongwith 5-FU also significantly declined the expression of drug transporters (ABCB1,ABCC5) and consequently resulted in an increased cellular uptake of 5-FU and its metabolite, 5-FdUMP at target site (colon). It could be possibly associated with change in permeability of cell membrane owing to the alteration in membrane fluidity. The present study revealed the mechanistic insights of FO as a MDR revertant which successfully restored 5-FU-mediated chemoresistance in experimental colon carcinoma.

Vitamin D: Its Deficiency and Effect of Supplementation on Maternal Outcome.

OBJECTIVES: Vitamin D deficiency is on a rise globally and so are the maternal complications related to it. This deficiency can be easily detected and corrected by simple oral supplementation for a better health outcome in pregnancy. METHODS: Antenatal women with no history of Vitamin D intake and first antenatal visit at our hospital between 26 to 28 weeks of gestation or after 34 weeks were tested for levels of Vitamin 25(OH)D. Deficient women (< 30 ng/ml) between 26 to 28 weeks were supplemented and tested again before delivery (Group A). Deficient women after 34 weeks who did not receive supplementation before delivery constituted Group B. Maternal outcome was noted and compared in both the groups. RESULTS: Out of the 189 Vitamin D deficient women included in the study; 105(55.5%) were enrolled in Group A and 84 (44.4%) in Group B. 24 (12.7%) women were severely deficient (<4 ng/ml), 134 (70.9%) were deficient (<20 ng/ml) and 28(14.8%) were vitamin D insufficient (20-30 ng/ml). A statistically significant reduction (<0.001) was observed in vitamin D deficient women after supplementation in group A. 5.7% women developed preeclampsia in group A as compared to 28.5% in group B (p<0.0001). Higher (13%) incidence of gestational diabetes mellitus was observed in group B as compared to group A (6.6%) though the difference was not significant. A significantly higher incidence of preterm labor was observed in group B (p=0.007). CONCLUSION: Vitamin D deficiency is correlated with a higher incidence of preeclampsia, gestational diabetes mellitus and preterm birth. Maternal screening in targeted population and its supplementation is recommended to improve maternal outcome.

Pre-Treatment Nutritional Status and Radiotherapy Outcome in Patients with Locally Advanced Head and Neck Cancers.

AIM: Poor oral intake and associated nutritional depletion can affect treatment outcome in locally advanced head and neck cancers. The aim of this study was to evaluate the pre radiotherapy nutritional status as a predictor for response to radiotherapy treatment. PATIENTS AND METHODS: Fifty patients of locally advanced head and neck cancers undergoing radical chemoradiotherapy were evaluated in this prospective analysis. Patients were treated with definitive radiotherapy to a total dose of 60-70 Gy along with concurrent chemotherapy with injection Cisplatin 100mg/m2 delivered three weekly. The patients were evaluated for pre-treatment nutritional status using the Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire. The PG-SGA evaluation was completed just before starting radiotherapy treatment and scores correlated to treatment outcome. RESULTS: Forty-seven male and three female patients were evaluated in this analysis. The median PG-SGA score was 8 with a range from 2-14.Grade 3-4 mucositis was seen in seven patients (21.8%) with PGSGA <9 compared to 55.5% in those with PG-SGA score = 9 (p=0.01). At the time of evaluation a complete response was seen in 16 patients (32%) with a PG-SGA score <9 compared to 4 patients (8%) with a PGSGA =9 (p=0.05). The median survival was 16±2.8months (Median ±S. Error) and 17±2.9 months in those with PG-SGA <9 and =9 respectively (p=0.49, log rank). CONCLUSION: PG-SGA nutritional score <9 is associated with a better local control and acute toxicity profile in radically treated head and neck cancer patients.

Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma.

5-Fluorouracil has been considered as a cornerstone therapy for colorectal cancer; however, it suffers from low therapeutic response rate and severe side effects. Therefore, there is an urgent need to increase the clinical efficacy of 5-fluorouracil. Recently, fish oil rich in n-3 polyunsaturated fatty acids has been reported to chemosensitize tumor cells to anti-cancer drugs. This study is designed to understand the underlying mechanisms of synergistic effect of fish oil and 5-fluorouracil by evaluation of tumor cell-associated markers such as apoptosis and DNA damage. The colon cancer was developed by administration of N,N-dimethylhydrazine dihydrochloride and dextran sulfate sodium salt. Further these animals were treated with 5-fluorouracil, fish oil, or a combination of both. In carcinogen-treated animals, a decrease in DNA damage and apoptotic index was observed. There was also a decrease in the expression of Fas, FasL, caspase 8, and Bax, and an increase in Bcl-2. In contrast, administration of 5-fluorouracil and fish oil as an adjuvant increased both DNA damage and apoptotic index by activation of both extrinsic and intrinsic apoptotic pathways as compared to the other groups. The increased pro-apoptotic effect by synergism of 5-fluorouracil and fish oil may be attributed to the incorporation of n-3 polyunsaturated fatty acids in membrane, which alters membrane fluidity in cancer cells. In conclusion, this study highlights that the induction of apoptotic pathway by fish oil may increase the susceptibility of tumors to chemotherapeutic regimens.

Mapping of adult plant stripe rust resistance genes in diploid A genome wheat species and their transfer to bread wheat.

Stripe rust, caused by Puccinia striiformis West. f.sp. tritici, is one of the most damaging diseases of wheat worldwide. Forty genes for stripe rust resistance have been catalogued so far, but the majority of them are not effective against emerging pathotypes. Triticum monococcum and T. boeoticum have excellent levels of resistance to rusts, but so far, no stripe rust resistance gene has been identified or transferred from these species. A set of 121 RILs generated from a cross involving T. monococcum (acc. pau14087) and T. boeoticum (acc. pau5088) was screened for 3 years against a mixture of pathotypes under field conditions. The parental accessions were susceptible to all the prevalent pathotypes at the seedling stage, but resistant at the adult plant stage. Genetic analysis of the RIL population revealed the presence of two genes for stripe rust resistance, with one gene each being contributed by each of the parental lines. A linkage map with 169 SSR and RFLP loci generated from a set of 93 RILs was used for mapping these resistance genes. Based on phenotypic data for 3 years and the pooled data, two QTLs, one each in T. monococcum acc. pau14087 and T. boeoticum acc. pau5088, were detected for resistance in the RIL population. The QTL in T. monococcum mapped on chromosome 2A in a 3.6 cM interval between Xwmc407 and Xwmc170, whereas the QTL from T. boeoticum mapped on 5A in 8.9 cM interval between Xbarc151 and Xcfd12 and these were designated as QYrtm.pau-2A and QYrtb.pau-5A, respectively. Based on field data for 3 years, their R2 values were 14 and 24%, respectively. T. monococcum acc. pau14087 and three resistant RILs were crossed to hexaploid wheat cvs WL711 and PBW343, using T. durum as a bridging species with the objective of transferring these genes into hexaploid wheat. The B genome of T. durum suppressed resistance in the F1 plants, but with subsequent backcrossing one resistance gene could be transferred from one of the RILs to the hexaploid wheat background. This gene was derived from T. boeoticum acc. pau5088 as indicated by co-introgression of T. boeoticum sequences linked to stripe rust resistance QTL, QYrtb.pau-5A. Homozygous resistant progenies with 40-42 chromosomes have been identified.