Day: February 16, 2022

‘A-Maize-ing’ Nanoparticles Target Cancer Cells Directly

Computer=generated depiction of nanoparticles

Researchers have recently developed novel nanoparticles derived from maize that can target cancer cells directly, via an immune mechanism. The results of this study, published in Scientific Reports, are encouraging, and the technique has demonstrated efficacy in treating tumour-bearing laboratory mice with no adverse effects.

Nanoparticles, or particles whose size varies between 1 and 100nm, have shown tremendous potential in many areas of science and technology, including therapeutics. However, conventional, synthetic nanoparticles are complicated and expensive to produce and alternatives such as extracellular vesicles (EVs) have mass production challenges.
Another recently emerging option is that of plant-derived nanoparticles (NPs), which can be easily produced in high levels at relatively lower costs. Like EVs, these nanoparticle-based systems also contain bioactive molecules, including polyphenols (which are known antioxidants) and microRNA, and they can serve as vehicles for targeted drug delivery.

Recently, researchers from the Tokyo University of Science (TUS) developed anti-cancer bionanoparticles, using corn (maize) as the raw material.
Lead researcher Professor Makiya Nishikawa explained: “By controlling the physicochemical properties of nanoparticles, we can control their pharmacokinetics in the body; so, we wanted to explore the nanoparticulation of edible plants. Maize, or corn, is produced in large quantities worldwide in its native form as well as in its genetically modified forms. That is why we selected it for our study.” 

The team centrifuged a super-sweet corn juice and then filtered it through a syringe filter with a 0.45μm pore size, then ultracentrifuged to obtain NPs derived from corn. The corn-derived NPs (cNPs) were approximately 80nm in diameter with a tiny net negative charge of -17mV.

The research team then set up experiments to see whether these cNPs were being taken up by various types of cells. In a series of promising results, the cNPs were taken up by multiple types of cells, including the clinically relevant colon26 tumor cells (cancer cells derived from mice), RAW264.7 macrophage-like cells, and normal NIH3T3 cells. RAW264.7 cells are commonly used as in vitro screens for immunomodulators.

The results were astounding: of the three types of cells, cNPs only significantly inhibited the growth of colon26 cells, indicating their selectivity for carcinogenic cell lines. Moreover, cNPs were able to successfully induce the release of tumour necrosis factor-α (TNF-α) from RAW264.7 cells. TNFα is primarily secreted by macrophages, natural killer cells, and lymphocytes, which help mount an anticancer response. “The strong TNFα response was encouraging and indicated the role of cNPs in treating various types of cancer,” explains Dr. Daisuke Sasaki, first author of the study and an instructor and researcher at TUS.

A luciferase-based assay revealed that the potent combination of cNPs and RAW264.7 cells significantly suppressed the proliferation of colon26 cells. Finally, the research team studied the effect of cNPs on laboratory mice bearing subcutaneous tumours. Once again, the results were astonishing: daily injections of cNPs into colon26 tumours significantly suppressed tumour growth, without causing serious side effects, or weight loss.

“By optimising nanoparticle properties and by combining them with anticancer drugs, we hope to devise safe and efficacious drugs for various cancers,” observed an optimistic Prof Nishikawa.

Source: Tokyo University of Science

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

High COVID Mortality Rate Found in African Children and Adolescents

Photo by Roman Nguyen on Unsplash

African children and adolescents hospitalised with COVID experience much higher mortality rates than Europeans or North Americans of the same age, according to a recent six-country study which included South Africa.

The study, published in JAMA Pediatrics. was conducted by researchers from the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) and the Institute of Human Virology Nigeria (IHVN). Both organisations are members of the Global Virus Network (GVN).

“This study provides important information about COVID among African children, which was not previously available at this scale. We now have evidence from multiple countries to show that African children also experience severe COVID; they experience multisystem inflammatory syndrome; some require intensive care; some also die, and at much higher rates than outside Africa,” said co-first author Nadia Sam-Agudu, MD, Associate Professor of Pediatrics at the UMSOM’s Institute of Human Virology.

The AFREhealth study collected data from 25 health facilities across Nigeria, Ghana, Democratic Republic of the Congo, Kenya, South Africa, and Uganda. The study included 469 African children and adolescents aged three months to 19 years hospitalised with COVID between March and December 2020. The team reported a high overall mortality rate of 8.3%, compared with 1% or less totaled from Europe and North America. Furthermore, African children less than a year old and with pre-existing, non-communicable diseases were more likely to have poorer outcomes.

Eighteen participants had suspected or confirmed multisystem inflammatory syndrome (also known as MIS-C), and four of these children died.

Dr Sam-Agudu, who led the West Africa team for the study, urged health authorities and policymakers in Nigeria and other African countries to act upon the study findings “to protect children by expanding vaccine approvals and procurements for children specifically, as the variants emerging since our study’s completion have either caused more severe disease and/or more cases overall. We cannot leave children behind in the pandemic response.”

Source: University of Maryland