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Background: Long non-coding RNAs (lncRNAs) play essential roles in molecular diagnosis and therapeutic response in several diseases. Purpose: For the first time, we aimed to evaluate the association of four lncRNAs TUG1 (rs7284767G/A), MIAT (rs1061540T/C), MALAT1 (rs3200401C/T), and SENCR (rs12420823C/T) variants with susceptibility to diabetic retinopathy (DR), disease severity, and early therapeutic response to intravitreous anti-vascular endothelial growth factor aflibercept therapy. Patients and Methods: This case-control study enrolled 126 adult patients with type 2 diabetes. TaqMan assays using Real-Time PCR were run for genotyping. Multivariable regression analyses were applied to assess the role of each polymorphism after the adjustment of covariates. Results: Carriers of TUG1 A/G and MIAT T/C and C/C genotypes were more likely to develop DR [OR=3.15 (95% CI=1.15-8.64), and OR=4.31 (95% CI=1.78-10.47)], while MALAT1 T/C conferred protection (OR=0.40, 95% CI=0.16-0.99). For TUG1, MALAT1, MIAT, and SENCR genotype combinations, GTCT and GCCC had a higher disease risk (P=0.012). For disease severity, MIAT T/T homozygosity was associated with higher DR grade [33.3% (T/T) vs 10% (C/C) and 4.2% (C/T) carriers, P=0.012]. Otherwise, patients with the SENCR T variant exhibited better pre-treatment best-corrected visual acuity level (p=0.021). Following aflibercept administration, carrying the TUG1 A or MIAT T/C was associated with a poor therapeutic response (OR=5.02, 95% CI=1. and OR=10.23, respectively). Conclusion:The lncRNAs TUG1 (rs7284767G/A) and MIAT (rs1061540T/C) were associated with increased DR susceptibility and poor response to aflibercept treatment, while MALAT1 (rs3200401C/T) conferred protection to DR. These genetic determinants could be useful in DR risk stratification and pharmacogenetics after validation in large-scale studies.

Full methodologies for MTT assay, Tubulin assay, flow cytometry, DNA fragmentation, RT-PCR genes expression analysis, and docking results for other compounds are supported as supplementary 1. Cell cultures and MTT assay A549, MCF-7 and GMSC cell lines were provided from the American Type Culture Collection (ATCC, USA) via VACERA Co. (Egypt). Cells were maintained and propagated in proper complete RPMI-1640/DMEM media l-Glutamine (Lonza Verviers SPRL, Belgium, cat#12-604F) which supplemented with 10% fetal bovine serum (FBS) (Seralab, UK, cat# EU-000-H), and 1% antibiotic (Antibiotic antimycotic, Biowest, cat# L0010). The cells were reared in humidified incubator with 5% CO2 at 37 °C, sub-cultured using 0.25% (w/v) trypsin/EDTA, and then counted using trypan blue staining and investigated under inverted microscope according to the standard tissue culture technique.The cytotoxic effects of the tested heterocyclic steroids on A549, MCF-7 and GMSC cell lines were evaluated by the cell viability colorimetric assay using MTT (3-[4,5methylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) dye. 5-FU is a standard reference drug was used as a positive control. Briefly, cell line (1×10 4 cells/well) were seeded in a 96-well plate in triplicate and were allowed to adhere for 24 h. Compounds were dissolved in 500 µl Dimethyl sulfoxide (DMSO) to have stock solution of 100 mM, then various concentrations of the tested derivatives or 5-FU were prepared by diluting in complete medium to have four final concentration of 1, 10, 100, and 1000 µM. Worth noting, the final concentration of DMSO in the culture medium didn't exceed 0.2% (v/v). Treated and non-treated cells were allowed to grow for 48 h. 10 μl of MTT (5 mg/ml in PBS w/o Ca, Mg, Lonza Verviers SPRL Belgium, cat#17-516F) was added in each well four hours before completion of incubation. After the incubation with MTT, color was developed by adding 100 μl of DMSO to each well and measured at 490 nm using Bio-Tek microplate reader. The experiment was conducted six times. Data were calculated as percent of cell viability by the following formula: % cell viability= (Mean absorbance in test wells / Mean absorbance in control wells) ×100, then IC50 was calculated using the Origin software.

Background The expression signature of deregulated long non-coding RNAs (lncRNAs) and related genetic variants is implicated in every stage of tumorigenesis, progression, and recurrence. This study aimed to explore the association of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene expression and the rs2383207A>G intronic variant with breast cancer (BC) risk and prognosis and to verify the molecular role and networks of this lncRNA in BC by bioinformatics gene analysis. Methods Serum CDKN2B-AS1 relative expression and rs2383207 genotypes were determined in 214 unrelated women (104 primary BC and 110 controls) using real-time PCR. Sixteen BC studies from The Cancer Genome Atlas (TCGA) including 8925 patients were also retrieved for validation of results. Results CDKN2B-AS1 serum levels were upregulated in the BC patients relative to controls. A/A genotype carriers were three times more likely to develop BC under homozygous (OR = 3.27, 95% CI 1.20–8.88, P = 0.044) and recessive (OR = 3.17, 95% CI 1.20–8.34, P = 0.013) models. G/G homozygous patients had a higher expression level [median and quartile values were 3.14 (1.52–4.25)] than A/G [1.42 (0.93–2.35)] and A/A [1.62 (1.33–2.51)] cohorts (P = 0.006). The Kaplan–Meier curve also revealed a higher mean survival duration of G/G cohorts (20.6 months) compared to their counterparts (A/A: 15.8 and A/G: 17.2 months) (P < 0.001). Consistently, BC data sets revealed better survival in cohorts with high expression levels (P = 0.003). Principal component analysis (PCA) showed a deviation of patients who had shorter survival towards A/A and A/G genotypes, multiple lesions, advanced stage, lymphovascular invasion, and HER2+ receptor staining. Ingenuity Pathway Analysis (IPA) showed key genes highly enriched in BC with CDKN2B-AS1. Conclusions The findings support the putative role of CDKN2B-AS1 as an epigenetic marker in BC and open a new avenue for its potential use as a therapeutic molecular target in this type of cancer.

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Background Colorectal Cancer is found one of the most profound type of cancer around globe, affecting men and women with different ethnic and racial groups. Insulin-like growth factor 1 is known as peptide growth factor found to increase the proliferation of cell and prevent apoptosis. Insulin pathway might have linked with progression of colorectal cancer. Methods This study conducted on total 160 subjects, including 80 patients with colorectal cancer with 80 age and gender match controls. Clinical parameters were compared between the control group and Colorectal cancer group. Blood serum IGF-1 was quantified by using ELISA and IGF-1 rs6214(C/T) variations were investigated using TaqMan allelic discrimination assay. Results Blood serum level of Insulin growth factor-I (ng/ml) showed substantial association concerning groups while IGF-1 rs6214(C/T) genotype distribution observed increased in colorectal cancer patients as compared to controls with significant association. The variant TT and CT genotype frequency observed more common in cases as compared to control. However, the wild type CC genotype were common in cases used to compared with controls. The Odds Ratio reveal the risk of variant IGF-1 rs6214 T allele to increase 3 times compared to wild type allele. Conclusion The homozygous TT genotypes and T variant allele of IGF-1 rs6214(C/T) showed association with high serum Insulin growth factor level 1, may increase susceptibility to the colorectal cancer. This work will use to investigate the associations between Insulin-like growth factor 1 and rs6214(C/T) gene variant and blood serum level with the vulnerability to treat Colorectal. In summary, we have investigated the relationship between Insulin growth factor level hormone and colorectal cancer. Further studies are required to understand the association between colorectal cancer and polymorphism. However, this study can be serve as an informative study to uncover mechanisms behind main cause of colon cancer. Therefore, the genomic profiling of Insulin-like growth factor-1 can be helpful to treat colorectal cancer patients.

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Antipsychotics (APs) are mainly used as long-term medications for many psychiatric conditions, such as schizophrenia, bipolar disorder and Alzheimer's disease. 1,2 The number of individuals receiving APs worldwide is surprisingly high. 3 APs are classified as either old typical (conventional) or newer atypical APs with different common side effects, including extrapyramidal manifestations, 4 atropine-like action 5 and metabolic disorders. 6 Since the mid-1960s, AP treatment was associated with the aggravation of already existing DM or the development of new-onset type II DM with reported higher risk of hyperglycaemic emergencies. 7-12