Effects of Low-Dose Gestational TCDD Exposure on Behavior and on Hippocampal Neuron Morphology and Gene Expression in Mice.

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and toxic environmental pollutant. Gestational exposure to TCDD has been linked to cognitive and motor deficits, and increased incidence of autism spectrum disorder (ASD) traits in children. Most animal studies of these neurodevelopmental effects involve acute TCDD exposure, which does not model typical exposure in humans. OBJECTIVES: The aim of the study was to establish a dietary low-dose gestational TCDD exposure protocol and performed an initial characterization of the effects on offspring behavior, neurodevelopmental phenotypes, and gene expression. METHODS: Throughout gestation, pregnant C57BL/6J mice were fed a diet containing a low dose of TCDD (9 ng TCDD/kg body weight per day) or a control diet. The offspring were tested in a battery of behavioral tests, and structural brain alterations were investigated by magnetic resonance imaging. The dendritic morphology of pyramidal neurons in the hippocampal Cornu Ammonis (CA)1 area was analyzed. RNA sequencing was performed on hippocampi of postnatal day 14 TCDD-exposed and control offspring. RESULTS: TCDD-exposed females displayed subtle deficits in motor coordination and reversal learning. Volumetric difference between diet groups were observed in regions of the hippocampal formation, mammillary bodies, and cerebellum, alongside higher dendritic arborization of pyramidal neurons in the hippocampal CA1 region of TCDD-exposed females. RNA-seq analysis identified 405 differentially expressed genes in the hippocampus, enriched for genes with functions in regulation of microtubules, axon guidance, extracellular matrix, and genes regulated by SMAD3. DISCUSSION: Exposure to 9 ng TCDD/kg body weight per day throughout gestation was sufficient to cause specific behavioral and structural brain phenotypes in offspring. Our data suggest that alterations in SMAD3-regulated microtubule polymerization in the developing postnatal hippocampus may lead to an abnormal morphology of neuronal dendrites that persists into adulthood. These findings show that environmental low-dose gestational exposure to TCDD can have significant, long-term impacts on brain development and function. https://doi.org/10.1289/EHP7352

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Micropropagation and conservation of selected endangered anticancer medicinal plants from the Western Ghats of India

Globally, cancer is a constant battle which severely affects the human population. The major limitations of the anticancer drugs are the deleterious side effects on the quality of life. Plants play a vital role in curing many diseases with minimal or no side effects. Phytocompounds derived from various medicinal plants serve as the best source of drugs to treat cancer. The global demand for phytomedicines is mostly reached by the medicinal herbs from the tropical nations of the world even though many plant species are threatened with extinction. India is one of the mega diverse countries of the world due to its ecological habitats, latitudinal variation, and diverse climatic range. Western Ghats of India is one of the most important depositories of endemic herbs. It is found along the stretch of south western part of India and constitutes rain forest with more than 4000 diverse medicinal plant species. In recent times, many of these therapeutically valued herbs have become endangered and are being included under the red-listed plant category in this region. Due to a sharp rise in the demand for plant-based products, this rich collection is diminishing at an alarming rate that eventually triggered dangerous to biodiversity. Thus, conservation of the endangered medicinal plants has become a matter of importance. The conservation by using only in situ approaches may not be sufficient enough to safeguard such a huge bio-resource of endangered medicinal plants. Hence, the use of biotechnological methods would be vital to complement the ex vitro protection programs and help to reestablish endangered plant species. In this backdrop, the key tools of biotechnology that could assist plant conservation were developed in terms of in vitro regeneration, seed banking, DNA storage, pollen storage, germplasm storage, gene bank (field gene banking), tissue bank, and cryopreservation. In this chapter, an attempt has been made to critically review major endangered medicinal plants that possess anticancer compounds and their conservation aspects by integrating various biotechnological tool

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS: We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS: Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION: Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. FUNDING: Bill & Melinda Gates Foundation

A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales