TIGR–Tas represents the first modular, PAM-free, multi-segment RNA-guided genome-editing system, expanding the conceptual and technical boundaries of precision editing beyond CRISPR-based paradigms. This architecture combines compact effector proteins with multiple short RNA guides that define non-contiguous DNA targets, introducing a fundamentally distinct mode of sequence recognition and cleavage. The absence of PAM constraints, together with guide modularity and reduced protein size, addresses persistent limitations related to delivery, target accessibility, and engineering flexibility. Emerging evidence indicates that TIGR–Tas systems can be programmed for precise DNA manipulation. Their compact architecture and modular guide organization may facilitate streamlined vector packaging and customizable guide-array design, although these potential advantages require further experimental validation. Nevertheless, critical gaps remain in defining specificity, repair outcomes, ortholog diversity, and immunogenicity. Resolving these issues through systematic characterization will determine the translational potential of TIGR–Tas as a complementary platform for precision genome engineering and therapeutic innovation.
Autoimmune diseases represent an important global health concern, with notable sex- and age-related differences in prevalence and susceptibility. This narrative review summarizes current evidence on associations between exposure to toxic metals and metalloids, particularly mercury (Hg), arsenic (As), cadmium (Cd), and lead (Pb), and autoimmune-related outcomes, with emphasis on endocrine, metabolic, oxidative, and immunological mechanisms. Relevant literature was identified through PubMed, Scopus, and Google Scholar, with human cohort, case–control, cross-sectional, ecological, and biomonitoring studies prioritized and mechanistic evidence used to support biological interpretation. Human studies have reported associations between toxic-metal exposure or altered metal burden and systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, type 1 diabetes mellitus, and celiac disease, although the consistency of these associations varies considerably across diseases and study designs. Proposed mechanisms include disruption of hormone receptor signalling and hypothalamic-pituitary axes, oxidative and mitochondrial stress, inflammatory signalling, altered Th1/Th17 and regulatory T-cell responses, epigenetic changes, and impaired immune tolerance. However, most available epidemiological evidence is observational, and differences in blood, urine, hair, tissue, or cord-blood metal concentrations do not establish temporality or causality. Evidence is comparatively more consistent for autoimmune thyroid disease, rheumatoid arthritis, and multiple sclerosis, whereas findings for systemic lupus erythematosus are more heterogeneous and evidence for type 1 diabetes mellitus and celiac disease remains limited. Further prospective and longitudinal studies are needed to clarify exposure–response relationships, critical developmental windows, and population-specific susceptibility in women and children.
Transmembrane serine protease 6 (TMPRSS6) gene polymorphisms have been associated with alterations in iron status and hematological parameters linked to iron homeostasis. Among the reported TMPRSS6 variants, rs855791 (c.2207 T > C; p.V736A) is the most consistently replicated and the only common variant with a demonstrated functional effect on iron metabolism. This study was conducted to analyse the impact of TMPRSS6 (rs855791) gene polymorphism on serum ferritin level and erythrocyte indices in a pediatric cohort evaluated for anemia, comprising children with and without iron deficiency anemia (IDA). TMPRSS6 (rs855791) genotyping was performed in 282 children suspected of anemia. Clinical data, complete blood counts and serum ferritin were recorded, and associations between genotypes (including dominant and recessive models), hematological parameters and iron status were assessed. Children were categorized on the basis of serum ferritin level into IDA (n = 70) and non-IDA (n = 212) groups. The genotype and allele frequencies did not differ significantly between the two groups, indicating no association between rs855791 and the risk of IDA. Serum ferritin was lowest in the ‘TT’ genotype, intermediate in ‘TC’ and highest in ‘CC’, following a graded (allele-dose) pattern, and mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were nominally lower in the ‘TT’ genotype. In the pre-specified age- and sex-adjusted additive models, each additional ‘C’ allele was associated with higher ferritin, MCV, MCH and hemoglobin, and these associations withstood Benjamini–Hochberg correction (all q ≤ 0.042), whereas the unadjusted three-genotype comparisons did not (q = 0.052–0.087). In conclusion, in this pediatric cohort TMPRSS6 (rs855791) showed evidence of association with serum ferritin, the erythrocyte indices MCV and MCH, and hemoglobin as continuous traits—most convincingly as an allele-dose trend in multivariable models—rather than with the risk of IDA itself.
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among women of reproductive age and is associated with reproductive dysfunction, chronic low-grade inflammation, and metabolic disturbances. However, the extent to which hematological and biochemical abnormalities vary across different body mass index (BMI) categories has not been adequately investigated, limiting our understanding of the independent contributions of adiposity and PCOS to these alterations. This case–control study included 191 women diagnosed with PCOS using Rotterdam criteria and an equal number of age-matched apparently healthy controls. Complete blood count, renal function, liver function, and lipid profile parameters were compared between groups. In the present study we found that women with PCOS exhibited significantly higher white blood cell count, hematocrit, mean platelet volume, granulocyte percentage, urea, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and liver enzyme levels (AST, ALT, and ALP), along with significantly lower high-density lipoprotein cholesterol and serum albumin compared with controls (all p values < 0.05). BMI-stratified analyses revealed that overweight/obese women with PCOS had the most pronounced hematological and metabolic abnormalities. However, unlike controls, significant alterations in the indicators of inflammatory and metabolic dysfunction were also observed in normal-weight and lean women with PCOS. These findings suggest that such disturbances may represent inherent features of the syndrome, rather than consequences of obesity alone.
