Host genetic variants associated with COVID-19 reconsidered in a Slovak cohort.

We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2'-5'-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype 'gttg' carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.

Metabolomic profiling of blood plasma of patients with lung cancer and malignant tumors with metastasis in the lungs showed similar features and promising statistical discrimination against controls.

Targeting metabolomic pathways is a promising strategy for cancer treatment. Alterations in the metabolomic state have also an epigenetic impact, making the metabolomic studies even more interesting. We explored metabolomic changes in the blood plasma of patients with primary and secondary lung cancer and tried to explore their origin. We also applied a discrimination algorithm to the data. In the study, blood samples from 132 patients with primary lung cancer, 47 with secondary lung cancer, and 77 subjectively healthy subjects without any cancer history were used. The samples were measured by NMR spectroscopy. PCA and PLS-DA analyses did not distinguish between patients with primary and secondary lung tumors. Accordingly, no significantly changed levels of plasmatic metabolites were found between these groups. When comparing with healthy controls, significantly increased glucose, citrate, acetate, 3-hydroxybutyrate, and creatinine balanced with decreased pyruvate, lactate, alanine, tyrosine, and tryptophan were found as a common feature of both groups. Metabolomic analysis of blood plasma showed considerable proximity of patients with primary and secondary lung cancer. The changes observed can be partially explained as cancer-derived and also as changes showing ischemic nature. Random Forrest discrimination based on the relative concentration of metabolites in blood plasma performed very promising with AUC of 0.95 against controls; however noticeable parts of differencing metabolites are overlapping with those observed after ischemic injury in other studies.

Implications of flavonoids as potential modulators of cancer neovascularity.

PURPOSE: The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients. METHODS: This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research. RESULTS AND CONCLUSION: Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.