Search Results (33)

Background: There is an abundance of the neuroactive β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) in grass pea (Lathyrus sativus), pea (Pisum sativum), and several Chinese traditional herbs such as Panax notoginseng. It is well known for its dose- and context-dependent effects on its toxicological characteristics (inducing neurodegenerative neurolathyrism upon excessive consumption) or for its pharmacological effects (including neuroprotection and wound healing). Therefore, reducing β-ODAP levels improves the safety profile of β-ODAP-containing species for utilization, whereas increasing them facilitates their isolation and purification. LsBAHD3 acyltransferase, named after the first letter of BEAT benzylalcohol O-acetyltransferase (BEAT), anthocyanin O-hydroxycinnamoyltransferase (AHCT), anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT), and deacetylvindoline 4-Oacetyltransferase (DAT), was proven to be β-ODAP synthetase. Methods: In this report, the interaction of miR172f with LsBAHD3 was investigated through bioinformatic analysis and transient co-expression assays in Nicotiana benthamiana. Functions of miR172f in β-ODAP biosynthesis were also investigated through knockdown in the hairy roots of L. sativus and via transcriptomic analysis. Results: The results suggest that the knockdown of miR172f in hairy roots of L. sativus increased β-ODAP content via targets to LsBAHD3. In this process, protein ubiquitination, cysteine and methionine metabolism, enzyme regulator activity, and so on were associated with β-ODAP biosynthesis. Conclusions: These results identify miR172f as a novel regulator of β-ODAP biosynthesis through targeting of LsBAHD3, offering new insight into the gene expression of β-ODAP synthetase and the genetic network governing β-ODAP biosynthesis in L. sativus. Full article

Background/Objectives: This study aimed to analyze the relationship between various anthropometric measurements (Body Mass Index (BMI), Clínica Universidad de Navarra-Body Adiposity Estimator (CUNBAE), hip and waist circumference (WC), weight, and height) and Triple-Negative Breast Cancer (TNBC) according to menopausal status. Methods: A total of 113 TNBC cases and 226 matched controls from the MCC-Spain study were included. Controls were matched by age, educational level, family history, and province. Conditional logistic regression models, stratified by menopausal status, were used to estimate adjusted Odds Ratios (aORs) and their 95% Confidence Intervals (95% CIs) for the association between anthropometric measures and TNBC risk. Results: A divergent non-significant trend was observed: compared to their respective controls, premenopausal cases tended to have lower mean anthropometric measurements (except height), while postmenopausal cases showed higher means. No statistically significant associations were observed for individual measures derived from logistic regressions. However, when comparing women with normal BMI and normal WC (the reference group), a non-significant association of risk was found in those premenopausal women who were centrally obese (normal weight/high WC) (aOR = 1.79; 95% CI = 0.17–18.29), but the combination of overweight and a large WC showed an aOR of 0.22 (95% CI = 0.03–1.68) before menopause. In contrast, the combination of overweight and a high WC showed a statistically significant adjusted OR of 3.28 in postmenopausal women (95% CI = 1.10–9.81). Conclusions: Our findings suggest that the relationship between adiposity and TNBC is inverse in premenopausal women and direct in postmenopausal women, highlighting the importance of considering both body fat distribution and menopausal status when evaluating TNBC. However, our findings are limited by low statistical power, which may have led to a lack of statistical significance, and there is a need for larger, collaborative studies. Full article

Background: Surgical resection for ampullary lesions lacks clear guidelines. Pancreaticoduodenectomy (PD) is the standard treatment for malignant ampullary tumors but is often excessive for ampullary adenomas (AAs) due to its high morbidity and mortality. Transduodenal ampullectomy (TDA) is generally reserved for small benign lesions where endoscopic treatment fails, but its role in early ampullary cancers is debatable. This study presents our 25-year outcomes with TDA for benign ampullary tumors. Methods: We conducted a retrospective cohort study with prospectively collected data from patients with benign ampullary lesions who underwent TDA between January 1996 and November 2023. Primary outcomes were the 30-day overall and severe (Clavien–Dindo ≥ IIIa) morbidity rates and the 90-day mortality rate. Categoric variables were presented as absolute and relative frequencies, and quantitative variables were presented as means (standard deviation, SD) or medians (range or interquartile range, IQR). Results: Fifty-three patients (29 male; mean [SD] age 62.5 [14.6] years) underwent TDA. The 30-day morbidity rate was 32.1% (17/53 patients), with five (9.4%) cases being severe. The 90-day mortality rate was 1.9%. Definitive histopathology identified 38 (71.7%) AAs and five (9.4%) infiltrating ampullary adenocarcinomas, two (40.0%) of which required subsequent PD. Six (11.3%) patients experienced recurrence. Overall, nine (16.9%) patients died. Conclusions: TDA is a safe and effective technique with acceptable morbidity for non-infiltrating lesions, especially in patients with poor clinical status. Choosing between TDA and PD depends on tumor size, dysplasia grade, and institutional expertise. Lifelong endoscopic surveillance post-TDA is essential for timely recurrence detection. Full article

Grass pea (Lathyrus sativus L.) is a nutritious legume crop well-adapted to fragile agro-ecosystems that can survive under challenging climatic conditions. The cultivation of grass pea faces stigma primarily due to the presence of β-N-Oxalyl-L-α, β-diaminopropionic acid (β-ODAP), which is associated with a risk of inducing neurolathyrism upon prolonged consumption of its grains as a staple diet. The grass pea improvement program of the International Center for Agricultural Research in the Dry Areas (ICARDA) aims to reduce β-ODAP content to a safe level along with improving yield potential and nutritional quality of grass pea. In this study, 183 germplasm accessions representing 13 different Lathyrus species and 11 L. sativus breeding lines were evaluated for β-ODAP content based on Rao protocol and mineral concentration using ICP-OES. Significant variability was observed among the accessions for the studied traits. The results showed low β-ODAP content and high mineral concentration in 25 accessions of crop wild relatives, which included L. cicera, L. ochrus, and L. cassius, with one accession IG65277 of L. cassius, in addition to two lines, IG117034 and ACC1335, of L. sativus having very low β-ODAP content. Furthermore, some accessions of L. pseudocicera, L. aphaca, L. cicera, L. marmoratus, L. gorgoni, and L. tingitanus also showed low β-ODAP content. The results showed significant positive correlations among different trait combinations, viz., K and P (r = 0.193 ***), K and Fe (r = 0.177 ***), Mn and Fe (r = 0.210 ***), Mn and Se (r = 0.137 ***), β-ODAP and Mg (r = 0.158 **), and β-ODAP and Ca (r = 0.140 **). L. cicera, L. ochrus, and L. cassius were identified as a great source for improving the mineral concentration and reducing β-ODAP content in the cultivated grass pea. Full article

Grasspea (Lathyrus sativus L.) is a climate-smart legume crop with adaptation to fragile agroecosystems. The genus Lathyrus is recognized for its vast genetic diversity, encompassing over 160 species, many of which are cultivated for various purposes across different regions of the world. Among these, Lathyrus sativus is widely cultivated as food, feed, and fodder in South Asia, Sub-Saharan Africa, and the Central and West Asia and North Africa (CWANA) regions. Its global cultivation has declined substantially due to the stigma posed by the presence of neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP) in its seeds and green foliage. Overconsumption for a longer period of grasspea seeds harvested from landraces may lead to a neurological disorder called neurolathyrism in humans. ODAP is an obstacle for grasspea expansion, but crop wild relatives (CWRs) have been found to offer a solution. The incorporation of CWRs, particularly Lathyrus cicera, and landraces into breeding programs may reduce the ODAP content in grasspea varieties to a safer level. Recent advances in genomics-assisted breeding have expanded the potential for utilizing challenging CWRs to develop grasspea varieties that combine ultra-low ODAP levels with improved yield, stability, and adaptability. Further progress in omics technologies—such as transcriptomics, proteomics, and metabolomics—along with genome sequencing and editing, has greatly accelerated the development of grasspea varieties with reduced or zero ODAP content, while also enhancing the plant’s agronomic value. This review highlights the significance of utilizing CWRs in pre-breeding programs, and harnessing advanced tools and technologies to enhance the performance, adaptability, and resilience of grasspea in response to changing environmental conditions. Full article

Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP) and its association with neurolathyrism. Though some varieties with low β-ODAP have been developed through classical breeding, the β-ODAP content is increasing due to genotype x environment interactions. This review covers grass pea nutritional quality, β-ODAP biosynthesis, mechanism of paralysis, traditional ways to reduce β-ODAP, candidate genes for boosting sulfur-containing amino acids, and the potential and targets of gene editing to reduce β-ODAP content. Recently, two key enzymes (β-ODAP synthase and β-cyanoalanine synthase) have been identified in the biosynthetic pathway of β-ODAP. We proposed four strategies through which the genes encoding these enzymes can be targeted and suppressed using CRISPR/Cas9 gene editing. Compared to its homology in Medicago truncatula, the grass pea β-ODAP synthase gene sequence and β-cyanoalanine synthase showed 62.9% and 95% similarity, respectively. The β-ODAP synthase converts the final intermediate L-DAPA into toxic β-ODAP, whist β-cyanoalanine synthase converts O-Acetylserine into β-isoxazolin-5-on-2-yl-alanine. Since grass pea is low in methionine and cysteine amino acids, improvement of these amino acids is also needed to boost its protein content. This review contains useful resources for grass pea improvement while also offering potential gene editing strategies to lower β-ODAP levels. Full article

(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases. (2) Methods: We analyzed data from 436 participants from the BarcUVa-Seq population-based cross-sectional study utilizing gene expression profiles (RNA-Seq) from frozen colonic mucosal biopsies and dietary information from a semi-quantitative food frequency questionnaire. Dietary variables were evaluated based on two dietary patterns and as individual variables. Differential expression gene (DEG) analysis was performed for each dietary factor using edgeR. Protein–protein interaction (PPI) analysis was conducted with STRINGdb v11 for food groups with more than 10 statistically significant DEGs, followed by Reactome-based enrichment analysis for the resulting networks. (3) Results: Our findings reveal that food intake, specifically the consumption of blue fish, alcohol, and potatoes, significantly influences gene expression in the colon of individuals without tumor pathology, particularly in pathways related to DNA repair, immune system function, and protein glycosylation. (4) Discussion: These results demonstrate how these dietary components may influence human metabolic processes and affect the risk of bowel diseases. Full article

NAFLD has emerged as a significant public health concern, with its prevalence increasing globally. Emphasizing the complex relationship between dietary patterns and epigenetic modifications such as DNA methylation or miRNA expression can exert a positive impact on preventing and managing metabolic disorders, including NAFLD, within the 2030 Sustainable Development Goals. This review aims to evaluate the influence of dietary patterns on hepatic epigenetic gene modulation and provide dietary recommendations for the prevention and management of NAFLD in the general population. Methods: Comprehensive screening and eligibility criteria identified eleven articles focusing on epigenetic changes in NAFLD patients through dietary modifications or nutrient supplementation. Results and Discussion: Data were organized based on study types, categorizing them into evaluations of epigenetic changes in NAFLD patients through dietary pattern modifications or specific nutrient intake. Conclusions: The study highlights the importance of dietary interventions in managing and preventing NAFLD, emphasizing the potential of dietary patterns to influence hepatic epigenetic gene modulation. This study provides valuable insights and recommendations to mitigate the risk of developing NAFLD: (i) eat a primarily plant-based diet; (ii) increase consumption of high-fiber foods; (iii) consume more polyunsaturated and monounsaturated fatty acids; (iv) limit processed foods, soft drinks, added sugars, and salt; and (v) avoid alcohol. Full article

Physical activity (PA) is an established protective factor for colorectal cancer (CRC). However, the mechanisms underlying this relationship are less understood, and it is not known if the association is modified by genetic variants. To investigate this possibility, we conducted a genome-wide gene–PA interaction analysis. Using logistic regression and two-step and joint tests, we analyzed the interactions between common genetic variants across the genome and self-reported PA (categorized as active vs. inactive and as study- and sex-specific quartiles) in relation to CRC risk. PA had an overall protective effect on CRC, showing a 15% risk reduction among active vs. inactive participants (OR = 0.85; 95% CI = 0.81–0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant located between the GREM1 and SCG5 genes, and PA for CRC risk (p = 2.6 × 10⁻⁸). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant PA–CRC association was observed among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p = 3.5 × 10⁻⁸). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82). In summary, these results identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein-related, inflammatory and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis. Full article

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S ribosomal RNA (16S) gene sequencing. The primary obstacle is reconciling the differing outputs of these two methodologies, which often lead to divergent statistical models and conclusions. In this study, we introduce an algorithm designed to bridge this gap by mapping shotgun-derived taxa to their 16S counterparts. This mapping enables us to assess the predictive performance of a shotgun-based microbiome signature using 16S data. Our results demonstrate a reduction in performance when applying the 16S-mapped taxa in the shotgun prediction model, though it retains statistical significance. This suggests that while an exact match between shotgun and 16S data may not yet be feasible, our approach provides a viable method for comparative analysis and validation in the context of CRC-associated microbiome research. Full article

Grasspea (Lathyrus sativus L.) is recognized as a highly drought-tolerant legume. However, excessive consumption of its seeds and green tissues causes neurolathyrism, a condition characterized by an irreversible paralysis of the legs induced by a neurotoxin amino acid called β-N-oxalyl-L-α, β- diaminopropionic acid (β-ODAP). The present study investigated the effects of heat, and combined heat + drought during the reproductive phase on physiological and phenological parameters, yield-related factors, ODAP content, and seed protein of 24 genotypes representing 11 Lathyrus species under controlled conditions. Analysis of variance revealed a highly significant effect (p < 0.001) of stress treatments and genotypes for all the traits. In general, heat stress individually or in combination with drought expedited phenology, reduced relative leaf water content, stimulated proline synthesis, and influenced chlorophyll concentration; the effects were more severe under the combined heat + drought stress. ODAP content in seeds ranged from 0.06 to 0.30% under no-stress conditions. However, under heat stress, there was a significant increase of 33% in ODAP content, and under combined stress (heat + drought), the increase reached 83%. Crude protein content ranged from 15.64 to 28.67% among no stress plants and decreased significantly by 23% under heat stress and by 36% under combined stress. The findings of this study also indicated substantial reductions in growth and grain yield traits under both heat stress and combined heat + drought stress. Six accessions namely IG 66026, IG 65018, IG 65687, IG 118511, IG 64931, and IG65273 were identified as having the most favorable combination of yield, protein content, and seed ODAP levels across all conditions. ODAP content in these six accessions varied from 0.07 to 0.11% under no stress and remained at moderate levels during both heat stress (0.09–0.14%) and combined stress (0.11–0.17%). IG 66026 was identified as the most stable genotype under drought and heat stress conditions with high protein content, and low ODAP content. By identifying those promising accessions, our results have established a basis for forthcoming grasspea breeding initiatives while paving the way for future research exploration into the fundamental mechanisms driving ODAP variation in the presence of both heat and drought stress conditions. Full article

Grass pea (Lathyrus sativus L.), an indigenous legume of the subcontinental region, is a promising source of protein and other nutrients of health significance. Contrarily, a high amount of β-N-oxalyl-l-α,β-diaminopropionic acid (β-ODAP) and other anti-nutrients limits its wider acceptability as healthier substitute to protein of animal and plant origin. This study was aimed at investigating the effect of different processing techniques, viz. soaking, boiling, germination, and fermentation, to improve the nutrient-delivering potential of grass pea lentil and to mitigate its anti-nutrient and toxicant burden. The results presented the significant (p < 0.05) effect of germination on increasing the protein and fiber content of L. sativus from 22.6 to 30.7% and 15.1 to 19.4%, respectively. Likewise, germination reduced the total carbohydrate content of the grass pea from 59.1 to 46%. The highest rate of reduction in phytic acid (91%) and β-ODAP (37%) were observed in germinated grass pea powder, whereas fermentation anticipated an 89% reduction in tannin content. The lactic acid fermentation of grass pea increased the concentration of calcium, iron, and zinc from 4020 to 5100 mg/100 g, 3.97 to 4.35 mg/100 g, and 3.52 to 4.97 mg/100 g, respectively. The results suggest that fermentation and germination significantly (p < 0.05) improve the concentration of essential amino acids including threonine, leucine, histidine, tryptophan, and lysine in L. sativus powder. This study proposes lactic acid fermentation and germination as safer techniques to improve the nutrient-delivering potential of L. sativus and suggests processed powders of the legume as a cost-effective alternative to existing plant proteins. Full article

Vegetal diamine oxidase (vDAO), an enzyme proposed to relieve symptoms of histaminosis, shows better reactivity with histamine and aliphatic diamines, as well as higher enzymatic activity than DAO of animal origin. The objective of this study was to evaluate the enzyme activity of vDAO from germinating grains from Lathyrus sativus (grass pea) and Pisum sativum (pea), and to verify the presence of a neurotoxin, β-N-Oxalyl-L-α,β-diaminopropionic acid (β-ODAP), in the crude extract obtained from their seedlings. A targeted liquid chromatography–multiple-reaction monitoring mass spectrometry method was developed and used to quantify β-ODAP in the analysed extracts. An optimized sample preparation procedure, involving protein precipitation with acetonitrile followed by mixed-anion exchange solid-phase extraction, allowed for high sensitivity and good peak shape for β-ODAP detection. The Lathyrus sativus extract exhibited the highest vDAO enzyme activity of the extracts, followed by the extract from pea cultivar Amarillo from the Crop Development Centre (CDC). The results have also shown that even though β-ODAP was present in the crude extract from L. sativus, its content was far below the toxicity threshold (300 mg of β-ODAP/kg body/day). CDC Amarillo showed 5000-fold less β-ODAP than the undialysed L. sativus extract. It was concluded that both species can be considered as convenient sources of vDAO for potential therapeutic use. Full article

Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8–17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6–9.2), and median OS (mOS) of 20.6 months (95% CI 13.6–28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2–22.2] and 10.3 [IQR 7.4–14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5–8.6) versus 7.5 months (95% CI 6.5–10.1, p = 0.03), and 16.4 (95% CI 9.3–27.5) versus 24.2 months (95% CI 17.2–NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients. Full article

The gut microbiome is a potential modifiable risk factor for colorectal cancer (CRC). We re-analyzed all eight previously published stool sequencing data and conducted an MWAS meta-analysis. We used cross-validated LASSO predictive models to identify a microbiome signature for predicting the risk of CRC and precancerous lesions. These models were validated in a new study, Colorectal Cancer Screening (COLSCREEN), including 156 participants that were recruited in a CRC screening context. The MWAS meta-analysis identified 95 bacterial species that were statistically significantly associated with CRC (FDR < 0.05). The LASSO CRC predictive model obtained an area under the receiver operating characteristic curve (aROC) of 0.81 (95%CI: 0.78–0.83) and the validation in the COLSCREEN dataset was 0.75 (95%CI: 0.66–0.84). This model selected a total of 32 species. The aROC of this CRC-trained model to predict precancerous lesions was 0.52 (95%CI: 0.41–0.63). We have identified a signature of 32 bacterial species that have a good predictive accuracy to identify CRC but not precancerous lesions, suggesting that the identified microbes that were enriched or depleted in CRC are merely a consequence of the tumor. Further studies should focus on CRC as well as precancerous lesions with the intent to implement a microbiome signature in CRC screening programs. Full article