The association between 3020INSC mutation in NOD2 gene and arterial stiffness in hypertensives

Background The innate immune system elicits an inflammatory process which is believed to be involved in the development of vascular damage in hypertension. The NOD2 gene (CARD15) is involved in the control of the innate immune system. The aim of this study was to assess the occurrence of the 3020insC mutation in the NOD2 gene in relation to vascular damage in hypertensives. Materials and methods In 466 hypertensives, genotyping for 3020insC mutation, cholesterol, serum creatinine, and echocardiography were carried out. Systolic (SBP) and diastolic (DBP) blood pressure and pulse pressure (PP) were taken at 2-3 month intervals for one year and treated according to ESC/ESH guidelines. Results The 3020insC mutation was found in 7.08% of hypertensives and was associated with earlier onset of hypertension 48.2 &#177; 12.1 v. 42.8 &#177; 10.9, p < 0.01 (age of pts). After one year of treatment, patients with the mutation had significantly higher SBP (138.48 &#177; 18.35 v. 131.74 &#177; 14.97, p < 0.04) and PP (57.27 &#177; 14.04 v. 52.70 &#177; 12.96, p < 0.04) than patients without the mutation, whereas the number of drugs was the same in both groups. Conclusions The results suggest that the 3020insC mutation is associated with earlier onset of hypertension and increased arterial stiffness

The association between 3020INSC mutation in NOD2 gene and arterial stiffness in hypertensives.

The innate immune system elicits an inflammatory process which is believed to be involved in the development of vascular damage in hypertension. The NOD2 gene (CARD15) is involved in the control of the innate immune system. The aim of this study was to assess the occurrence of the 3020insC mutation in the NOD2 gene in relation to vascular damage in hypertensives

NOD2/CARD15 polymorphism in patients with rectal cancer.

Reports published in the past several years have not provided conclusive evidence regarding a relationship between the development of colorectal cancer and NOD2 gene mutations, though some geographic variability has been shown. The goal of the current project was to analyze the frequency of selected NOD2 gene variants, including P286S, R702W, G908R, and 1007fs, in the Polish population of patients with rectal cancer. Fifty-one rectal cancer patients undergoing treatment were included in the study. As a control group to provide a reference point for NOD2 polymorphism in the population, DNA obtained from cord blood collected from the placenta of 100 patients immediately after parturition was used. It was found that the aforementioned mutations were more frequent among the colorectal cancer patients and that the presence of the 1007fs variant might also be associated with young patient age. The analysis of the material does not allow presenting a conclusive answer as to whether the 1007fs, G908R, and R702W mutations or P268S polymorphism contribute to the development of sporadic colorectal cancer in the Polish population. Patients in some populations could likely benefit from instituting earlier colorectal cancer screening studies following the detection of the 1007fs mutation

The outline of immunopathogenesis of Crohn's disease with special consideration of NOD2/CARD15 gene polymorphism.

Crohn sdisease is achronic inflammatory disease affecting different parts of digestive tract. Despite the extensive research, t here is still no exact explanation of its pathogenesis. In the paper we present modern views on the origin of the disorder, concerning the influence o f infectious, immu- nological, neuroendocrine and molecular factors on the disease development. We pay special attention to the role of NOD2/CARD15 gene in the pathogenesis of inflammatory bowel disease.Choroba Le niowskiego-Crohna jest przewlek³¹ chorob¹ zapaln¹ przewodu pokarmowego atakuj¹c¹ ró¿ne jego odcinki. Mimo intensywny ch ba- dañ, jak dot¹d nie uda³o siê ustaliæ dok³adnie jej patogenezy. Wpracy przedstawiono najnowsze pogl¹dy na temat mechanizmów pows tawania tej choroby obejmuj¹ce wp³yw czynników inf ekcyjnych, neuroendokrynnych, immunologiczn ych iinnych. Szczególny nacisk po³o¿ono na znacze- nie uwarunkowañ genetycznych. Omówiono równie¿ biologiczne funkcje oraz kluczow¹ rolê genu NOD2/CARD15 wprocesie powstawania prze- wlek³ych chorób zapalnych przewodu pokarmoweg

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future

Anti-SARS-CoV-2 IgG against the S Protein: A Comparison of BNT162b2, mRNA-1273, ChAdOx1 nCoV-2019 and Ad26.COV2.S Vaccines

Background: COVID-19 vaccines induce a differentiated humoral and cellular response, and one of the comparable parameters of the vaccine response is the determination of IgG antibodies. Materials and Methods: Concentrations of IgG anti-SARS-CoV-2 antibodies were analyzed at three time points (at the beginning of May, at the end of June and at the end of September). Serum samples were obtained from 954 employees of the Nicolaus Copernicus University in Toruń (a total of three samples each were obtained from 511 vaccinated participants). IgG antibody concentrations were determined by enzyme immunoassay. The statistical analysis included comparisons between vaccines, between convalescents and COVID-19 non-patients, between individual measurements and included the gender, age and blood groups of participants. Results: There were significant differences in antibody levels between mRNA and vector vaccines. People vaccinated with mRNA-1273 achieved the highest levels of antibodies, regardless of the time since full vaccination. People vaccinated with ChAdOx1 nCoV-2019 produced several times lower antibody levels compared to the mRNA vaccines, while the antibody levels were more stable. In the case of each of the vaccines, the factor having the strongest impact on the level and stability of the IgG antibody titers was previous SARS-CoV-2 infection. There were no significant correlations with age, gender and blood type. Summary: mRNA vaccines induce a stronger humoral response of the immune system with the fastest loss of antibodies over time

The Dynamics of Changes in the Concentration of IgG against the S1 Subunit in Polish Healthcare Workers in the Period from 1 to 12 Months after Injection, Including Four COVID-19 Vaccines

Background: The presented research made it possible to obtain the characteristics of changes in anti-SARS-CoV-2 IgG within one year of vaccination in healthcare workers. Materials and Methods: The research group consisted of 18,610 participants represented by medical and administration staff. IgG antibody concentrations were determined by ELISA. Results: At 5–8 months after full vaccination, the levels of anti-SARS-CoV-2 IgG with equal vaccines were similar. The exception was JNJ-78436735, for which IgG levels were significantly lower. In the 9th month after vaccination, an increase in the anti-SARS-CoV-2 IgG level, suggesting asymptomatic infection, was observed in a large group of participants. Significantly higher levels of anti-SARS-CoV-2 IgG antibodies were observed after the booster dose compared to the second dose. The increase in antibodies was observed already around the 5th day after the injection of the booster dose, and was maximized at approximately the 14th day. Conclusion: The cut-off date for protection against the disease seems to be the period 8–9 months from the vaccination for mRNA vaccines and 5–6 months for vector vaccines. The introduction of a booster dose was the right decision, which could have a real impact on restricting the further transmission of the virus

Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast Cancer

Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C&gt;T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6&ndash;1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene