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Cytokines coordinate the intricate choreography of the immune system, directing cellular activities that mediate inflammation, pathogen defense, pathology and tissue repair. Within this spectrum, the anti-inflammatory prowess of interleukin-10 (IL-10) predominates in immune homeostasis. In normal pregnancy, the dynamic shift of IL-10 across trimesters maintains maternal immune tolerance ensuring fetal development and pregnancy success. Unravelling the dysregulation of IL-10 in pregnancy complications is vital, particularly in the heightened inflammatory condition of preeclampsia. Of note, a reduction in IL-10 levels contributes to endothelial dysfunction. In human immunodeficiency virus (HIV) infection, a complex interplay of IL-10 occurs, displaying a paradoxical paradigm of being immune-protective yet aiding viral persistence. Genetic variations in the IL-10 gene further modulate susceptibility to HIV infection and preeclampsia, albeit with nuanced effects across populations. This review outlines the conceptual framework underlying the role of IL-10 in the duality of normal pregnancy and preeclampsia together with HIV infection, thus highlighting its regulatory mechanisms and genetic influences. Synthesizing these findings in immune modulation presents avenues for therapeutic interventions in pregnancy complications comorbid with HIV infection. [ABSTRACT FROM AUTHOR]

Context: Dengue is one of the important vector‑borne viral diseases affecting humans with diverse manifestations. Toll‑like receptors (TLR) are pattern recognition receptors and play an important role in innate immunity against microbes. TLR3 plays a critical role in controlling the innate immune response mediated by flaviviruses such as dengue. Aim: We attempted to study the susceptibility of single nucleotide polymorphism of the TLR3 gene in dengue encephalitis (DE) patients and determine the association in terms of genotype, allele, and haplotype distribution along with the clinical outcome. Settings and Design: It was a case‑controlled observational study in a tertiary care hospital. Methods and Material: We investigated the single nucleotide polymorphism in the TLR3 Leu412Phe gene using real‑time polymerase chain reaction in 29 cases of DE and compared them with equal number of age‑ and sex‑matched dengue patients without neurological features. Statistical Analysis Used: The genotype and allele frequencies were compared using a two‑sided Chi‑square or Fisher’s exact test. Results: The findings revealed that the genotypic distribution of TLR3 Leu412Phe polymorphism for the mutant genotype Phe/Phe (TT) demonstrated increased association of DE (31.03% vs 6.8%, P 0.019, odds ratio 6.075, 95% confidence interval 1.181–31.245). However, the number of heterozygous (H) genotype (Leu/ Phe–CT) and mutant Phe allele (T) did not show any statistically significant association. TLR3 gene polymorphism did not show any correlation with mortality outcome at 1 month. Conclusion: The presence of mutant TLR3 Leu412Phe polymorphism may confer the propensity to have DE in patients with dengue infection in the Indian population. TLR3 polymorphism did not affect mortality outcome at 1 month. [ABSTRACT FROM AUTHOR]

Epigenetic machinery is a cornerstone in normal cell development, orchestrating tissue-specific gene expression in mammalian cells. Aberrations in this intricate landscape drive substantial changes in gene function, emerging as a linchpin in cancer etiology and progression. While cancer was conventionally perceived as solely a genetic disorder, its contemporary definition encompasses genetic alterations intertwined with disruptive epigenetic abnormalities. This review explores the profound impact of DNA methylation, histone modifications, and noncoding RNAs on fundamental cellular processes. When these pivotal epigenetic mechanisms undergo disruption, they intricately guide the acquisition of the 6 hallmark characteristics of cancer within seemingly normal cells. Leveraging the latest advancements in decoding these epigenetic intricacies holds immense promise, heralding a new era in developing targeted and more efficacious treatment modalities against cancers driven by aberrant epigenetic modifications. [ABSTRACT FROM AUTHOR]

Background: There is evident inter-individual variability in women's responses to Chlamydial infections and reproductive tract problems. Women's genetic variations within the Interleukin-10 (IL-10) gene have been linked to variances in response to Chlamydia trachomatis infection. This study was aimed to demonstrate the profound association of IL-10 with infertility and demonstrate the role of IL-10 (-592 C/A rs1800872) and (-1082 A>G rs1800896) single nucleotide polymorphism (SNPs) gene in the susceptibility and severity of a C. trachomatis infection. Method: In this evaluation study, serum IL-10 concentration was measured in 134 women diagnosed with infertility and 50 healthy volunteers by enzyme-linked immunosorbent assay (ELISA). The tetraamplification refractory mutation system-PCR (T-ARMS-PCR) analysis was performed to detect the genotyping of the rs1800872 and rs1800896 SNPs genes. Result: Both female groups were positive for anti-chlamydial IgM antibody, but the intensity of response differed between cases. At the same time, the incidence of genital C. trachomatis by PCR was 46.2% in infertile women. The serum concentration of IL10 was lower in infertile women than healthy participants and higher in infertile C. trachomatis-positive women compared to infertile C. trachomatis-negative in all groups except endometriosis (Endo) infertility. In rs1800872, the CA genotype and C allele are associated with an increased risk for infertility, except in polycystic ovarian syndrome (PCOS), which is an A allele. In the case of rs1800896, the AG genotype and G allele show a greater risk for infertility. Conclusions: Our results confirmed that rs1800872 and rs1800896 gene polymorphisms were associated with an increased risk of C. trachomatis infection. [ABSTRACT FROM AUTHOR]