Medical Bulletin 29/ August/ 2024

Here are the top health news for the day:

How Manuka Honey Might Help with Breast Cancer?

A recent study reported in the Journal Nutrients outlined the promising role of Manuka Honey, in prevention and treatment of breast cancer(1).

In 2022, approximately 2.3 million women globally were diagnosed with breast cancer, which ranks as the second most prevalent cancer worldwide(2). Around 80% of breast cancer cases are estrogen receptor-positive (ER-positive), indicating that the cancer cells have receptors that attach to estrogen and may depend on the hormone for their growth.

Treatment options for estrogen receptor-positive breast cancer currently include surgery, chemotherapy, radiation therapy, and hormonal therapy. Previous research has also explored complementary and alternative medicine (CAM) for treating estrogen receptor -positive breast cancer. This includes antioxidant supplements, yoga, mindfulness practices, and acupuncture.

Current study now suggest that Manuka honey might serve as an alternative prevention and treatment option for breast cancer(3), especially estrogen receptor -positive breast cancer, based on studies using animal and cancer cell models.

Manuka honey is produced by bees that gather nectar from the Manuka tree, native to Australia and New Zealand.

In this study, researchers employed both mouse and breast cancer cell models to investigate the effects of Manuka honey on breast cancer(4). They discovered that Manuka honey led to an 84% reduction in tumour growth in mice with estrogen receptor -positive breast cancer cells, while not adversely affecting healthy breast cells or causing significant side effects.

Scientists found that higher quantities of Manuka honey were linked to a more significant decrease in cancer cell growth(5). Furthermore, the research indicated that Manuka honey helped lower the activity of signaling pathways commonly elevated in cancer, such as AMP-activated protein kinase (AMPK), Ak strain transforming (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3), all of which are involved in tumor cell growth and survival.

Reference: Márquez-Garbán DC, Yanes CD, Llarena G, Elashoff D, Hamilton N, Hardy M, Wadehra M, McCloskey SA, Pietras RJ. Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models. Nutrients. 2024; 16(14):2369. https://doi.org/10.3390/nu16142369

New Affordable, Rapid Diagnostic Tool To Detect Brain Cancer

A recent research published in Communications Biology has discovered an automated device capable of diagnosing glioblastoma, a fast-growing and incurable brain cancer, in less than an hour(6).

The core of the diagnostic tool is a biochip that utilises electrokinetic technology to identify biomarkers, specifically active Epidermal Growth Factor Receptors (EGFRs). These receptors are commonly overexpressed in cancers like glioblastoma and are present in extracellular vesicles(7).

Researchers faced two main challenges: developing a method to differentiate between active and inactive Epidermal Growth Factor Receptors and designing a diagnostic technology that could both detect and selectively identify active Epidermal Growth Factor Receptors on extracellular vesicles from blood samples(8).

To address these issues, they designed a biochip featuring a low-cost electrokinetic sensor roughly the size of a ballpoint pen’s ball(9). This sensor’s small size allows antibodies on it to form multiple attachments to individual extracellular vesicles, which greatly improves the diagnostic's sensitivity and selectivity.

Additionally, synthetic silica nanoparticles are used to “report” the presence of active Epidermal Growth Factor Receptors on the captured extracellular vesicles by carrying a high negative charge. When active Epidermal Growth Factor Receptors are present, a voltage shift occurs, signalling the detection of glioblastoma in the patient.

The device consists of three components: an automation interface, a portable prototype machine that dispenses materials for the test, and the biochip. Each test uses a new biochip, but both the automation interface and the prototype machine can be used multiple times.

Performing a test takes less than an hour and requires only 100 microliters of blood. The cost of materials for each biochip is under $2.

While the device was originally developed for glioblastoma, the researchers believe it can be adapted for detecting other types of biological nanoparticles(10). This suggests that the technology could potentially be used to identify various biomarkers for other diseases.

Reference: Maniya, N.H., Kumar, S., Franklin, J.L. et al. An anion exchange membrane sensor detects EGFR and its activity state in plasma CD63 extracellular vesicles from patients with glioblastoma. Commun Biol 7, 677 (2024). https://doi.org/10.1038/s42003-024-06385-1

Gut Microbe Metabolites Can Modulate Heart Disease Risk

Recent clinical research has indicated that phenylacetylglutamine (PAGln), a newly identified metabolite produced by gut microbes, may influence the risk of developing cardiovascular disease (CVD) and heart failure (HF)(11).

A recent study published in Nature Communications investigates the mechanisms underlying the link between phenylacetylglutamine and negative cardiovascular effects(12).

Chronic non-communicable diseases account for nearly 75% of deaths worldwide. Cardiovascular diseases (CVDs), heart failure (HF), and related conditions represent a major portion of this mortality, highlighting the critical need to enhance current diagnostic and treatment methods.

As research progresses, the connection between diet, gut microbiota, and public health is becoming increasingly clear. Emerging evidence links gut microbial communities to various psychological and metabolic conditions, including obesity, diabetes, and Cardiovascular diseases risk.

Several studies have suggested that phenylacetylglutamine (PAGln) may be associated with adverse cardiovascular events, with some research using phenylacetylglutamine levels in blood and faeces as indicators to predict future Cardiovascular diseases risk.

This study is the first to show that a metabolite from the gut microbiome can act as a natural modulator (NAM) of a host receptor(13), indicating a significant coevolution between the microbiome and its host.

The research found that phenylacetylglutamine affects cardiovascular tissue in a condition-dependent manner, acting as a partial activator of the β2AR receptor(14). Additionally, PAGln was recognized as an "ago-allosteric modulator," a unique type of modulator that works both as an agonist and an allosteric modulator depending on its interaction with other substances.

Overall, these findings suggest that phenylacetylglutamine could be a promising target for developing new treatments for cardiovascular diseases(15) and that exploring the gut microbiome could offer new opportunities for tackling chronic illnesses.

Reference: Saha, P.P., Gogonea, V., Sweet, W. et al. (2024). Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors. Nature Communications 15; 6696. doi:10.1038/s41467-024-50855-3

Safety of Low-Intensity Blood Stem Cell Transplants for Lung Health in Sickle Cell Disease

Safety of Low-Intensity Stem Cell Transplants for Sickle Cell

A study published in the Annals of the American Thoracic Society indicates that low-intensity blood stem cell transplants, which involve milder conditioning agents than those used in standard transplants(16), do not appear to harm the lungs and may potentially improve lung function in some patients with sickle cell disease (SCD).

Damage to lung tissue and impaired lung function are significant complications and major causes of death in individuals with sickle cell disease, a severe blood disorder(17). The new study examines whether less intensive types of transplants, which are often better tolerated by many adults, contribute to or exacerbate lung damage on their own.

Until recently, bone marrow and blood stem cell transplants were the only available cure for sickle cell disease(18). However, relatively few adults have received these treatments due to the health risks associated with the high doses of chemotherapy needed to prepare for the transplants.

Additionally, the process requires a genetically compatible donor, typically a sibling without sickle cell disease. The procedure involves transplanting blood stem cells from the donor to produce healthy red blood cells that replace the defective, "sickled" cells. These sickled cells obstruct blood flow throughout the body, leading to numerous issues such as severe pain episodes, infections, stroke, and acute chest syndrome, which deprives the lungs of oxygen(19).

For the study, scientists examined 97 patients with sickle cell disease who received a low-intensity, or non-myeloablative, blood stem cell transplant between 2004 and 2019. The researchers performed various pulmonary function tests. The results indicate that low-intensity blood stem cell transplants, which use less harsh conditioning agents compared to standard transplants, do not seem to damage the lungs and may even improve lung function in some patients with sickle cell disease (SCD).

Reference: Ruhl, A. P., Shalhoub, R., Jeffries, N., Limerick, E. M., Leonard, A., Barochia, A. V., Tisdale, J. F., Fitzhugh, C. D., & Hsieh, M. M. (2024). Pulmonary function after non-myeloablative hematopoietic cell transplant for sickle cell disease. Annals of the American Thoracic Society. https://doi.org/10.1513/AnnalsATS.202309-771OC