Elevated concentrations of serum matrix metalloproteinase-2 and -9 and their associations with circulating markers of cardiovascular diseases in chronic arsenic-exposed individuals.

BACKGROUND: Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs. METHODS: A total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits. RESULTS: Serum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (r s = 0.208, p < 0.001 for MMP-2; r s = 0.163, p < 0.01 for MMP-9), hair (r s = 0.163, p < 0.01 for MMP-2; r s = 0.173, p < 0.01 for MMP-9) and nail (r s = 0.160, p < 0.01 for MMP-2; r s = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 µg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs. CONCLUSIONS: This study showed the significant positive associations and dose-response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.

Nutritional status of children with neurodevelopmental disorders: a cross-sectional study at a tertiary-level hospital in northern Bangladesh.

BACKGROUND: Malnutrition in children with neurodevelopmental disorders (NDDs) is a significant global public health issue. Nutritional assessment combined with management or advice are essential to produce optimal outcomes. OBJECTIVES: The objective of this study was to assess nutritional status and the sociodemographic profile of children with neurodevelopmental disorders in Bangladesh. METHODS: A cross-sectional study was conducted from December to April 2020 among the population of children with NDDs who presented to the pediatric department of the TMSS Medical College and Rafatullah Community Hospital in Bogura during this period. Socio-demographic data along with anthropometric measurements of the children were taken. Assessment of nutritional status were made using metrics such as z-scores for weight-for-age (WAZ), height-for-age (HAZ), and body mass index-for-age (BAZ). Descriptive statistics (number and percentage) and analytical statistics (chi-square and logistic regression) were included. RESULTS: 58.6% of children displayed malnutrition, with 47.8% showing undernutrition (WHZ / BAZ - 1 SD-≤-3 SD), and 10.8% overnutrition (BAZ > 2SD). Significant negative associations were found between malnutrition and parental education level, urban residency, and monthly family income. Children diagnosed with cerebral palsy exhibited twice the likelihood to be malnourished (AOR 2.39, 95% CI 0.83-6.87). Furthermore, residing in rural regions was associated with an increased risk of experiencing malnutrition, as indicated by an adjusted odds ratio of 1.60 (95% CI 0.12-3.09). CONCLUSIONS: While the results are cross-sectional, over half of children with NDDs were found to be malnourished, suggesting that children with NDD in Bangladesh are vulnerable to developing any form of malnutrition. Therefore, regular assessments and timely nutritional support may improve their situation.

Emerging of lysine demethylases (KDMs): From pathophysiological insights to novel therapeutic opportunities.

In recent years, there have been remarkable scientific advancements in the understanding of lysine demethylases (KDMs) because of their demethylation of diverse substrates, including nucleic acids and proteins. Novel structural architectures, physiological roles in the gene expression regulation, and ability to modify protein functions made KDMs the topic of interest in biomedical research. These structural diversities allow them to exert their function either alone or in complex with numerous other bio-macromolecules. Impressive number of studies have demonstrated that KDMs are localized dynamically across the cellular and tissue microenvironment. Their dysregulation is often associated with human diseases, such as cancer, immune disorders, neurological disorders, and developmental abnormalities. Advancements in the knowledge of the underlying biochemistry and disease associations have led to the development of a series of modulators and technical compounds. Given the distinct biophysical and biochemical properties of KDMs, in this review we have focused on advances related to the structure, function, disease association, and therapeutic targeting of KDMs highlighting improvements in both the specificity and efficacy of KDM modulation.