Synergistic polyphenol blends containing curcumin and pomegranate ellagitannins have been reported to improve exercise recovery via reduced muscle injury and optimized inflammatory response. The purpose of the present study was to use molecular biomarkers to identify specific innate immune response pathways that may be improved by supplementation with a synergistic polyphenol blend. Participants were randomized to either synergistic polyphenol blend (SPC; 1000 mg/d of standardized curcuminoids and pomegranate ellagitannins; Restoridyn®; Verdure Sciences; n = 13) or placebo (n = 14) for 28-d prior to running a half marathon. Venous blood samples were collected at PRE, 2H, and 4H after running a half mara-thon and isolated RNA was analyzed for the expression of 774 mRNA associated with 40 immune response pathways using a standardized panel. With SPC, at 2H pathways had attenuated activation (T-cell Activation, NK Cell Cytotoxicity), blunted activation (Type 1 IFN), and reduced suppression (JAK-STAT, Inflammatory Signaling, Lipid Metabolism, and Stress Response/DNA Damage). The average differential expression change with SPC at 2H reflected 25
BackgroundIn colorectal cancer the most frequently analyzed markers are RAS/RAF mutations which have negative predictive role for anti-EGFR antibody therapy. Although the hotspot mutations of the K- and NRAS exon 2-4 are well defined, the predictive role of rare mutations of other codons are questionable and the current guidelines are less precise in this respect.MethodsWe have retrospectively re-analyzed the full spectrum of RAS/RAF mutations by next-generation sequencing (NGS) in a small cohort of nineteen cetuximab treated metastatic colorectal cancer patients whose enrollment was based on KRAS exon 2 mutation analysis.ResultsWe have detected 13 rare RAS/RAF mutations where 5 occurred together with hotspot (HSP) mutations. In the five non-HSP mutant cases we have detected 8 rare/non-HSP RAS/RAF mutations: KRAS-E37.,C51Y, NRAS-D57N,E62K,G60E/V14I, HRAS-P34L and BRAF-G464R. Kaplan-Meier analysis indicated that the progression free survival (PFS) of non-HSP cases ran parallel with wild type (WT) cases separately from the HSP mutant cases without statistical significance (p = 0.156). However, the combination of WT group with non-HSP cases resulted in a near significant survival difference from HSP cases (p = 0.057, HR = 3.501). Kaplan-Meier analysis of the overall survival (OS) again demonstrated that the survival curve of WT cases ran parallel with non-HSP cases, clearly separated from the HSP cases (p = 0.024). Overall survival of WT cases was significantly different as compared to HSP cases (p = 0.005) with HR of 6.362 (CI 1.496–27.055) as expected, while it was not statistically different from non-HSP cases (p = 0.092) with a HR of 0.891 (CI 0.248–3.205).ConclusionIn this small retrospective study we showed that the analyzed non-HSP mutations of RAS/RAF in colorectal cancer treated with cetuximab do not have negative effect on the efficacy. Since our cohort is very small and do not have accordingly the necessary statistical power of the survival analyses, therefore can only be considered as hypothesis generating one of the issue of the predictive role of non-hotspot RAS mutations on cetuximab efficacy.
BackgroundFetal adenocarcinoma of the lung (FLAC) is a rare subtype of lung adenocarcinoma resembling the developing fetal lung at the pseudoglandular stage (8–16 weeks of gestation). This study investigates the clinicopathological features, along with key diagnostic and treatment considerations for FLAC.MethodsClinical data from 10 FLAC patients diagnosed at Linyi People’s Hospital between January 2017 and December 2024 were retrospectively analyzed. Their clinicopathological characteristics were summarized in conjunction with relevant literature.ResultsThe cohort comprised low-grade FLAC (L-FLAC, 6 cases) and high-grade FLAC (H-FLAC, 4 cases). Pathological examinations indicated higher frequencies of pleural invasion (3/4) and lymph node metastasis (1/4) in H-FLAC, which exhibited marked nuclear atypia and abundant mitoses, while L-FLAC demonstrated mild cellular atypia and morular structures. Immunohistochemistry revealed universal positivity for TTF-1. Napsin A expression was noted in both L-FLAC (3/3) and H-FLAC (2/4). In L-FLAC, β-catenin showed nuclear/cytoplasmic or nuclear expression in the vast majority of cases while H-FLAC displayed only membranous expression. Molecular testing detected an EGFR exon 19 deletion in one H-FLAC case and a KRAS G12C mutation in another. No recurrence was observed during follow-up, which ranged from 4 to 93 months.ConclusionFLAC exhibits distinctive morphological features and immunophenotypes, necessitating differential diagnosis from primary pulmonary tumors and metastatic malignancies. Surgical resection remains the primary therapeutic strategy. No disease recurrence was observed during follow-up from 4 to 93 months, although some patients had a shorter follow-up period of 4–6 months.
Despite the importance of healthy diet, adherence to dietary recommendations remains low. This may reflect individual differences in dietary intake that arise from environmental and genetic factors, including hormonal regulation, sex differences, and biological drivers of food preference. Genome-wide association studies (GWAS) have identified hundreds of loci associated with dietary intake, but the X-chromosome, a major source of sex-linked genetic variation, has largely been excluded. We applied multiple X-chromosome-wide association study (X-WAS) models to dietary intake phenotypes to identify novel loci and sex-specific effects. We performed X-WAS of 46 dietary intake traits from food frequency questionnaires in European-ancestry UK Biobank (UKB) participants (N = 424,758). Phenotypes included quantitative measures (e.g., fruit intake), binary traits (e.g., decaffeinated vs. caffeinated coffee), and principal component-derived food groups. We tested five X-WAS models: a traditional sex-combined additive model, sex-stratified additive models, a joint model that accounts for sex-interactions, and a model for non-additive genetic effects. We assessed generalizability across six ancestry groups, conducted a multi-ancestry meta-analysis (N = 445,773), and sought replication of female-specific findings in Women’s Genome Health Study (WGHS; N = 23,129). To characterize the biological context of associated loci, we performed phenome-wide association studies and covariate sensitivity analysis of known confounders of diet. We identified 18 loci associated with 20 dietary traits (P<5 × 10− 8), including two with prior evidence of biological mechanisms related to dietary behavior (GPR173 and HTR2C). Five loci had stronger associations in models accounting for sex-specific effects, including one locus with a significant SNP-by-sex interaction (rs191475305 associated with meat intake), highlighting the importance of considering unique X-chromosome biology. Eight of nine tested loci demonstrated consistent effects across ancestry groups in UKB (heterogeneity P > 0.05), and two of six loci replicated in WGHS (P < 0.05). Our study uncovers novel loci associated with dietary intake and provides evidence that sex-linked genetic variation contributes to individual differences in dietary intake. While most associations were detectable using conventional sex-combined analyses, models accounting for sex-specific and non-additive effects produced the strongest associations on several occasions. These findings establish the X-chromosome as an important component of dietary intake genetic architecture and demonstrate the value of robust X-chromosome models for genetic discovery.
Cichorium intybus L. (chicory) is a globally utilized medicinal plant whose root contains bioactive compounds such as inulin, fructose, chlorogenic acids (CGA), and sesquiterpene lactones (STL). These metabolites are central to its health-promoting properties. This study employed an integrated transcriptomic analysis to elucidate the genetic and molecular mechanisms underlying the effects of these compounds in mice. Microarray datasets (GSE150218 and GSE190056) were analyzed to identify differentially expressed genes (DEGs), hub genes, and associated microRNAs (miRNAs). Gene ontology (GO) enrichment, KEGG pathway analysis, and protein–protein interaction (PPI) networks were applied to characterize functional relevance. Distinct hub genes were identified: Rps28 and Rps2 (inulin), Rplp0, Cct2, and Rps20 (fructose), Mki67, Egfr, and Pparg (STL), and Socs2, Six2, Smtnl2, and Gcsh (CGA). Pathway enrichment revealed significant associations with mRNA surveillance, PPAR signaling, AMPK signaling, ribosome, and coronavirus-related pathways. Furthermore, miRNA analysis highlighted strong predicted regulatory interactions between miRNAs and hub genes, including mmu-miR-204-3p (inulin), mmu-miR-17-5p (fructose), mmu-miR-15a-5p (STL), and mmu-miR-142a-5p (CGA). Collectively, these findings identify molecular pathways and regulatory interactions associated with major chicory root bioactive compounds and provide a basis for future mechanistic studies. Experimental validation is required to confirm these predicted regulatory networks.
