Repurposing metformin as a potential anticancer agent using in silico technique.

BACKGROUND: The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion. OBJECTIVE: This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer. METHODS: A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool. RESULTS: 9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin. CONCLUSION: This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

[Comparative Analyses of IgA Antibody Response of Non-COVID-19 Infected People Over 60 Years Old Following CoronaVac and Pfizer-BioNTech COVID-19 Vaccination]. / COVID-19 Enfeksiyonu Geçirmeyen 60 Yas Üstü Kisilerde CoronaVac ve Pfizer-BioNTech Asisi Sonrasi IgA Antikor Yaniti Karsilastirilmasi.

The formation rate, magnitude, and duration of the antibody-mediated humoral immune response that develops against different viral proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are considered important in vaccine success. It is known that the response to vaccinations decreases due to immunosenescence in older adults. This study was aimed to investigate the levels of serum IgA response at 1st and 3rd month after vaccination of people over 60 years old who were immunized with CoronaVac and Pfizer-BioNTech. A total of 35 people living in the North Cyprus who have not previously had COVID-19 infection were included in the study. After the 2nd dose of vaccination, serum IgA levels were measured after the 1st and 3rd month with the anti-SARS-CoV-2 IgA (Euroimmun, Lubeck, Germany) kit. The statistical significance was determined as 0.05 in the whole study. SPSS and GraphPad Prism software were used for calculations, analyses and graphs. The possible effect of demographic variables on serum IgA level was compared between the vaccine groups and it was found that there was no statistically significant difference between them. For the IgA titer-positive individuals who had been vaccinated with the Pfizer-BioNTech vaccine, for both 1st and 3rd months were observed to be higher than CoronaVac vaccinated IgA titer-positive individuals. In individuals who received the CoronaVac vaccine, there was a statistically significant change in serum IgA levels between 1st and 3rd months, but there was no statistically significant change in the Pfizer-BioNTech vaccine administered group. When the Pfizer/BioNTech and CoronaVac vaccines were compared with each other in terms of serum IgA antibody titers, it was found that the mean serum IgA levels of the individuals in the Pfizer/BioNTech group were statistically higher at the 1st and 3rd months than the CoronaVac group. Serum IgA titers in both vaccine groups were statistically significantly decreased from 1st month to 3rd month. This study showed that the Pfizer/BioNTech vaccine induced higher SARS-CoV-2 specific serum IgA antibodies than the CoronaVac vaccine and remained seropositive for a longer time in individuals aged 60 years and older. It is believed that the serum IgA levels that were determined may not reflect the serum IgA levels. However, these findings support the studies in other literature, showing that the Pfizer-BioNTech mRNA vaccine induces higher SARS-CoV-2 specific serum IgA antibodies than the inactive CoronaVac vaccine and that it remains seropositive for a longer period of time. This study is important as it is the first study to compare the SARS-CoV-2 IgA antibody responses of individuals over 60 years of age in the Turkish Republic of Northern Cyprus in two different vaccine groups.

Comparative humoral response of mRNA and inactivated vaccines against COVID-19 in healthy adults aged 60 years and older.

INTRODUCTION: A vaccine against coronavirus disease 2019 (COVID-19) is critically needed for older adults because of the increased morbidity and mortality rates. METHODOLOGY: In this prospective study, we analysed the titre magnitude of the IgG antibodies directed against the SARS-CoV-2 Spike Protein S1 (S1-RBD) antigen in both CoronaVac and Pfizer-BioNTech groups. The samples were tested to detect antibodies that bind to the receptor-binding domain of the spike protein of SARS-CoV-2 using the Enzyme-Linked Immunosorbent Assay (ELISA) technique with SARS-CoV-2 IgG II Quant. The cut-off value was > 50 AU/mL. GraphPad Prism software was used. Statistical significance was defined at p < 0.05. RESULTS: The CoronaVac group (12 females, 13 males) had a mean age of 69.64 ± 1.38 years. The Pfizer-BioNTech group (13 males, 12 females) had a mean age of 72.36 ± 1.44 years. The anti- S1-RBD titre decrease rate from the 1st to the 3rd month for CoronaVac and Pfizer-BioNTech groups was 74.31% and 86.48%, respectively. There was no statistically significant difference in the antibody titre between the 1st month and 3rd month for the CoronaVac group. However, there was a significant difference between the 1st and 3rd month in the Pfizer-BioNTech group. In addition, there was no statistically significant difference in the genders between the 1st and 3rd month of the antibody titres for both the CoronaVac Pfizer-BioNTech group. CONCLUSIONS: The levels of anti-S1-RBD, the preliminary outcome data of our study, represents one piece of the puzzle of humoral response and duration of vaccination protection.

High fetal bisphenol A exposure enhances IL22 secretion: A proinflammatory cytokine.

BACKGROUND: Bisphenol A (BPA) is an industrial product, widely used in human consumed types of equipment that can be transmitted orally, by inhalation or through dermal absorption and is detectable in many body fluids including cord blood. A correlation between BPA concentration in maternal serum and cord blood has been demonstrated previously, suggesting a possible transfer of BPA via the transplacental path. OBJECTIVE: Our objective is to determine the impact of cord blood BPA level on cytokine responses. METHODS: In this cross-sectional study, healthy pregnant women who delivered healthy newborns followed by the Obstetrics and Gynecology Department between September 2016 to June 2017 were enrolled. Cord blood samples were obtained and BPA and IL4, IL5, IL10, IL17, IL22, IFN gama and TGF beta levels were studied by ELISA. RESULTS: Among 197 deliveries, 176 of them were included in the study. Due to lack of cut-off value, BPA levels were stratified as percentiles. No statistically significant difference was detected in comparison of cytokine levels based on BPA concentrations below and above the 25th and 50th percentiles. Significantly higher IL22 levels (p = 0.007) and increased ratio of IL22/TGFß (p = 0.04) were detected in those with BPA level above 75th percentile (>19.16 ng/ml) compared to the below group. CONCLUSIONS: This in vivo real-life study demonstrated that very high BPA levels in cord blood of expectant mothers enhances IL22 secretion in cord blood which is a proinflammatory cytokine. Studies evaluating long term immunological effects on those highly exposed newborns are necessitated.

Epigenetic Alteration in Colorectal Cancer: A Biomarker for Diagnostic and Therapeutic Application.

Colorectal cancer (CRC) is the leading cause of cancer death worldwide. A crucial process that initiates and progresses CRC is various epigenetic and genetic changes occurring in colon epithelial cells. Recently, huge progress has been made to understand cancer epigenetics, especially regarding DNA methylation changes, histone modifications, dysregulation of miRNAs and noncoding RNAs. In the "epigenome" of colon cancer, abnormal methylation of genes that cause gene alterations or expression of miRNA has been reported in nearly all CRC; these findings can be encountered in the average CRC methylome. Epigenetic changes, known as driving events, are assumed to play a dominant part in CRC. Furthermore, as epigenetic changes in CRC become properly understood, these changes are being established as clinical biomarkers for therapeutic and diagnostic purposes. Progression in this area indicates that epigenetic changes will often be utilized in the future to prevent and treat CRC.

Characteristics of allergic proctocolitis in early infancy; accuracy of diagnostic tools and factors related to tolerance development.

OBJECTIVE: We aimed to overview clinical characteristics of FPIAP with the results of diagnostic tools like APT, SPT and fecal calprotectin levels and the factors associated with tolerance development. METHODS: All patients diagnosed FPIAP at the outpatient clinic between January 2015 and January 2019 were enrolled retrospectively. Data about clinical characteristics, APT or SPT results, fecal calprotectin levels, suspected triggering foods, diet and tolerance status were obtained from the hospital database program and analyzed. RESULTS: 169 infants with F/M ratio 78/91 were enrolled. The mean age of the study population was 3.68 months (1-35 months, mean age 3.68 ± 4.33). APT was performed 137 of the participants and 126 (92%) of them were positive to at least one food allergens, 14 (48.2%) patients had positivity to at least one of the food allergens on SPT. Specific IgE were done in 90 patients and 12 (13.3%) revealed positive results. Two groups of patients developing tolerance before and after 18 months of age were evaluated; mucoid diarrhea, family history allergic diseases, cow's milk sensitivity and multiple allergen triggers were statistically significant risk factors for delayed tolerance according to univariate logistic analysis. However, none of these factors were revealed statistical significance in multivariate logistic analysis. CONCLUSIONS: Our study revealed that APT may be a useful tool for programming the elimination diet in breastfeeding mothers. SPT, specific IgE and fecal calprotectin are not necessary for FPIAP management. Multivariate regression analysis showed that none of the evaluated parameters had statistically significant relationship with the tolerance development.

Planning and approach to allergen-specific immunotherapy in polyallergic patients.

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

Isolation of human CD4/CD8 double-positive, graft-versus-host disease-protective, minor histocompatibility antigen-specific regulatory T cells and of a novel HLA-DR7-restricted HY-specific CD4 clone.

Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4(+)/CD8(+) double-positive; 2) specific for an HLA class I-restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I-restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7-restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease-protective, minor H Ag-specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.