Since the initial discovery of the oncogenic activity of WNT ligands our understanding of the complex roles for WNT signaling pathways in lung cancers has increased substantially. In the current review, the various effects of activation and inhibition of the WNT signaling pathways are summarized in the context of lung carcinogenesis. Recent evidence regarding WNT ligand transport mechanisms, the role of WNT signaling in lung cancer angiogenesis and drug transporter regulation and the importance of microRNA and posttranscriptional regulation of WNT signaling are also reviewed.

Vitamin D deficiency is a global public health concern with significant implications for bone health and chronic disease prevention. Our aim was to summarize the evidence from Cochrane and other systematic reviews evaluating the benefits or harms of vitamin D fortification of staple foods for household use. In April 2023, we systematically searched Ovid MEDLINE, Embase, Epistemonikos and the Cochrane Database of Systematic Reviews for systematic reviews investigating the effects of vitamin D fortification of food in general populations of any age. We used Cochrane methodology and assessed the methodological quality of included studies using AMSTAR (A MeaSurement Tool to Assess Systematic Reviews). We assessed the degree of overlap among reviews. All outcomes included in systematic reviews were assessed. The protocol is registered in PROSPERO (registration number: CRD42023420991). We included 27 systematic reviews out of 5028 records for analysis. Overall, 11 out of 12 systematic reviews calculating pooled estimates reported a significant increase in serum 25(OH)D concentrations. The mean change in serum 25(OH)D concentrations per additional 100 units of vitamin D ranged from 0.7 to 10.8 nmol/L. Fortification of food with vitamin D showed a reduction in the prevalence of vitamin D deficiency based on high-certainty evidence. Parathormone (PTH) levels were described to decrease, bone mineral density to increase, while the effects on other bone turnover markers were inconsistent. Fortification did not significantly impact most anthropometric parameters, but it seemed to positively influence lipid profiles. In summary, fortification of food with vitamin D results in a reduction of vitamin D deficiency and might increase serum 25(OH)D concentrations, to varying extents depending on the fortified vehicle and population characteristics. Additionally, fortification may have a positive impact on bone turnover and lipid metabolism but may only have a limited effect on anthropometric parameters.

Apolipoprotein A5 (APOA5) gene variants have been shown to be associated with elevated TG levels; the T-1131C (rs662799) variant has been reported to confer risk for the metabolic syndrome in adult populations. Little is known about the APOA5 variants in pediatric population, no such information is available for pediatric obesity at all. Here we examined four haplotype-tagging polymorphisms (T-1131C, IVS3 + G476A [rs2072560], T1259C [rs2266788] and C56G [rs3135506]) and studied also the frequency of major naturally occurring haplotypes of APOA5 in obese children. The polymorphisms were analyzed in 232 obese children, and in 137 healthy, normal weight controls, using PCR-RFLP methods. In the pediatric patients we could confirm the already known adult subjects based association of -1131C, IVS3 + 476A and 1259C variants with elevated triglyceride concentrations, both in obese patients and in the controls. The prevalence of the APOA5*2 haplotype (containing the minor allele of T-1131C, IVS3 + G476A and T1259C SNPs together) was 15.5% in obese children, and 5.80% in the controls (p<0.001); multiple logistic regression analysis revealed that this haplotype confers susceptibility for development of obesity (OR=2.87; 95% CI: 1.29-6.37; p≤0.01). By contrast, the APOA5*4 haplotype (with -1131C alone) did not show similar associations. Our findings also suggest that the APOA5*5 haplotype (1259C alone) can be protective against obesity (OR=0.25; 95% CI: 0.07-0.80; p<0.05). While previous studies in adults demonstrated, that the APOA5 -1131C minor allele confers risk for adult metabolic syndrome, here we show, that the susceptibility nature of this SNP restricted to the APOA5*2 haplotype in pediatric obese subjects.

Post-harvest fungicides are frequently used on citrus peels to reduce post-harvest fungal contamination during the storage and transport of products. Despite these positive effects, fungicides can pose health risks to consumers. The aim of our study was to perform a genotoxicological risk assessment of imazalil, pyrimethanil, thiabendazole and their mixtures used as post-harvest treatments. A Salmonella mutagenicity Ames test and comet assay were performed to detect reverse mutation and assess DNA damage. Base-pair, frameshift mutations and metabolic activity were analyzed using the Ames test. In the comet assay, lymphocytes were treated with fungicides for 4 and 24 h. Thiabendazole was found to induce both frameshift and base-pair mutations in the Ames test despite the mutagenicity of both imzalil and pyrimethanil (p < 0.05). DNA-strand breaks were observed in lymphocytes, mainly with dimethyl-sulfoxide solvent fungicides (p < 0.05). The long-term exposure and consumption of fruits and vegetables treated with fungicides can increase the risks of developing genotoxic tumors. Our findings raise new questions about the health risks of fungicides and their mixtures to consumers. Further investigations are essential to explore the genotoxicological effects of fungicides on citrus peels.