Background: In the absence of primary care and prevailing associated social stigma, many patients of neural tube defects (NTDs) from remote areas die without getting any treatment. The high number of such untreated cases and unregistered deaths in these areas made us ponders to the fact that tertiary care center-based studies do not represent the true incidence of NTDs. Materials and Methods: We did a population-based survey for NTDs births of rural areas from Jaunpur to Ghazipur district in Eastern Uttar Pradesh. These districts are among the least developed areas of Northern India in Uttar Pradesh among other 17. Results: The data show an incidence of 7.48 per 1000 live births. Conclusion: Besides of unawareness regarding periconceptional folate supplementation, intensive effort is required to design adequately powered studies to search other key factors responsible for high prevalence of NTDs.
The challenges of conventional animal models and two-dimensional (2D) in vitro cell cultures in effectively forecasting human toxicity have prompted a significant shift towards New Approach Methodologies (NAMs). This development centers on advanced humanized in vitro co-culture models that offer improved physiological relevance for toxicological assessment. This perspective highlights the critical role of biomaterials in the creation of complex microenvironments. This study demonstrates how biomaterials effectively mimic the original extracellular matrix (ECM) through controlled compositional, structural, mechanical, and biochemical signals, thereby enabling the development of sophisticated 3D spheroids, organoids, and Organ-on-Chip systems. These biomaterial-enhanced platforms are essential for precise evaluation of immunotoxicity, as they promote human-specific immune responses and targeted immunomodulation, and for carcinogenicity, as they accurately replicate the tumor microenvironment, affect cancer cell behavior, and enable patient-derived models. Moreover, we underscore the synergistic amalgamation of these biomaterial-based models with omics technologies and computational methodologies (QSAR, AI/ML) for thorough molecular insights and rational design. Despite ongoing challenges in standardization and high-throughput compatibility, the strategic utilization of biomaterials is set to transform predictive toxicology, expedite drug discovery, and promote personalized medicine, thereby diminishing dependence on animal testing and improving human safety.
Purpose: Short stature is prevalent among children worldwide, particularly in developing countries. Various trace elements, including zinc, magnesium, iron, copper, chromium and selenium, are crucial for proper body development. The aim of this study is to explore the relationship between trace elements and TNF-α and IL-6 to elicit and possible pathway responsible for short stature. Methods: Two hundred and twenty samples were recruited for this study, 100 short statures and 120 controls were randomly selected. Six trace elements were measured using graphite furnace atomic absorption spectrometry. The concentrations of IL-6 and TNF-α in serum were assessed utilizing the Enzyme-Linked-Immunosorbent Assay (ELISA). Superoxide dismutase was also analysed to determine the oxidative stress response. Results: The study revealed notable distinctions in serum trace element levels of short stature. They exhibited significant lower levels of zinc and magnesium, alongside higher levels of copper. The altered Cu/Zn ratio seemed to have a positive correlation with short stature. Conversely, no significant disparities were observed in iron, chromium, and selenium levels. Furthermore, a significant rise was noted in proinflammatory marker TNF-α and cytokine IL-6. Additionally, superoxide dismutase was low in the short statures In silico study shows a high affinity of Zinc with TNF alpha. It may be suggested that inflammation at any time during childhood, with the rise in TNF alpha tightly binds with zinc and may have led to a decrease in zinc serum levels, altered redox homeostasis and resulted in short stature. Conclusion: The altered Cu/Zn ratio along with high TNF alpha and IL6 may be used as a marker for short stature in the initial years of growth in children before they reach maturity at the age of 18. Thereafter, introducing zinc supplementation could potentially enhance stature by mitigating TNF-alpha level. Further experimental studies will help to establish the exact role of zinc with TNF alpha in short stature.
With the growing evidence on the variable human susceptibility against COVID-19, it is evident that some genetic loci modulate the severity of the infection. Recent studies have identified several loci associated with greater severity. More recently, a study has identified a 50 kb genomic segment introgressed from Neanderthal adding a risk for COVID-19, and this genomic segment is present among 16% and 50% people of European and South Asian descent, respectively. Our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations, respectively, which appears to be responsible for the low case fatality rate among South Asian populations. This result was also consistent with the real-time infection rate and case fatality rate among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the real-time infection rates and case fatality rate in India. We found that the polymorphism present in the 50 kb introgressed genomic segment (rs10490770) did not show any significant correlation with the infection and case fatality rate in India.