IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

BACKGROUND: Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. METHODS: A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. CONCLUSIONS: IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

IL-18 and CD14 variants in chronic HBV predisposition: a case-control study with in silico analyses focused on transcription and splicing.

Hepatitis B virus (HBV), a vaccine-avoidable infection, is a health concern worldwide, leading to liver disorders such as acute self-constraint and chronic hepatitis, liver failure, hepatic cirrhosis, and even hepatocellular carcinoma if untreated. 'Immunogeneticprofiling', genetic variations of the pro- and anti-inflammatory cytokines responsible for regulating the immune responses, cause person-to-person differences and impact the clinical manifestation of the disease. The current experimental-bioinformatics research was conducted to examine whether promoteric IL-18-rs187238 C > G and -rs1946518 T > G and intronic CD14-rs2569190 A > G variations are associated with chronic HBV. A total of 400 individuals (200 in each case and control group) participated in the study and were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The data was also assessed bioinformatics-wise for conservation, genomic transcription and splicing, and protein interactions. Findings proposed that unlike the IL-18-rs1946518 T > G and CD14-rs2569190 A > G, the IL-18-rs187238 C > G is a protector against chronic HBV (odds ratio [OR] = 0.62, 95% confidence intervals [CI]: 0.46-0.83, and p = 0.002). The TG/CC/AA, TG/CC/AG, TT/CC/AG, and GG/CC/AA combined genotypes significantly increased chronic HBV risk (p < 0.05), while the IL-18 G/T and G/G haplotypes lessened it (p < 0.05). Moreover, IL-18-rs1946518 T > G is in the protected genomic regions across mammalian species. In contrast to the IL-18-rs1946518 T > G, IL-18-rs187238 C > G is likely to create novel binding sites for transcription factors, and the CD14-rs2569190 A > G presumably changed the ribonucleic acid splicing pattern. More research on larger populations and other ethnicities is required to authenticate these results.

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends.

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.

Relationship Between Genetic Polymorphisms in Cell Cycle Regulatory Gene TP53 and Polycystic Ovarian Syndrome: A Case-Control Study and In Silico Analyses.

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic condition with several potential causes. Insulin resistance is a hallmark of PCOS that often coexists with hirsutism, hyperandrogenism, being overweight, and hormonal imbalances. The functioning of multiple replication and transcription factors is regulated by tumor suppressor genes (TSGs), which play a crucial role in maintaining genomic integrity and controlling the cell cycle of granulosa cells. In the present study, we examined how three single nucleotide polymorphisms (SNPs) in TP53, a cell cycle regulatory gene, affect the risk of developing PCOS in a sample of an Iranian population. Genomic DNA was extracted from 200 PCOS patients and 200 healthy women to analyze TP53 rs17880604, rs1625895, and rs1042522 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings revealed that the majority of PCOS cases were overweight [25 < body mass index (BMI) < 30]. A positive association was observed between the TP53 rs1042522 SNP and the risk of PCOS under codominant heterozygous and overdominant genetic patterns (odds ratio > 1). Meanwhile, a negative association was observed between TP53 SNPs (rs1625895, rs17880604) and susceptibility to PCOS under codominant heterozygous and dominant models of inheritance (odds ratio < 1). Moreover, different genotype and haplotype combinations of rs17880604/rs1625895/rs1042522 conferred a decreased risk of PCOS in our population. We found no statistical difference in the frequency of TP53 genotypes between PCOS cases and/or controls in terms of BMI, waist circumference, prolactin level, and markers of lipid and carbohydrate profile (P > 0.05). Molecular dynamic prediction showed that the missense substitution in the 17p13.1 position (rs1042522) could change the properties and secondary structure of the p53 protein. As inherited risk factors, TP53 variations may play a  pivotal role in the pathogenesis of PCOS among Iranian women. Replicated population-based studies on other ethnicities are required to find the genetic contribution of variants of TP53, or SNPs located in other TSGs, to the etiology of this endocrine disease.

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study.

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0.029) and allelic C vs. T (OR = 0.028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2.81 for rs2961920) and codominant GG vs. AA (OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.