Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype. Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients. Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple Read more

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners. The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and Read more

Neutrophils flood lungs in severe COVID-19

In the lungs of severe COVID-19 patients, neutrophils camp out and release inflammatory cytokines and tissue-damaging Read more

hepatology

Some types of intestinal bacteria protect the liver

Certain types of intestinal bacteria can help protect the liver from injuries such as alcohol or acetaminophen overdose, according to Emory scientists led by pathologist Andrew Neish and physiologist Dean Jones.

The research was published on March 25 in Cell Metabolism.

“The composition of the microbiota, because of natural variation, dysbiosis, or supplementation with probiotics, can strongly affect how the liver processes both toxins and pharmacological agents, and thus have clinical consequences on how individuals respond to such exogenous chemicals,” Neish says.

While pretreatment with bacteria is needed for the observed effect in acute liver injury, probiotics or small molecule substitutes may be useful in the treatment of chronic liver diseases, the authors suggest.

In mice, oral administration of Lactobacillus rhamnosus or LGG could protect against liver damage brought on by alcohol or acetaminophen. Several labs had already observed a beneficial effect from LGG against liver injury, but the Emory research establishes an additional mechanism.

The protection comes from a small molecule metabolite produced by the bacteria called 5-MIAA (5-methoxyindoleacetic acid), activating the mammalian transcription factor Nrf2. Other types of bacteria did not produce 5-MIAA or activate Nrf2. While LGG is also known to improve the barrier function of the gut and dampen inflammation, liver-specific depletion of Nrf2 prevented LGG’s beneficial effects, suggesting that this is the primary mechanism of action. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

The unsweetened option

Pediatric hepatologist Miriam Vos is starting a new study testing the effects of a low-sugar diet in children with NAFLD (non-alcoholic fatty liver disease). The study is supported by the Nutrition Science Initiative and conducted in a partnership with UCSD/Rady Children’s Hospital, San Diego. See below for more on NUSI.

While there are no medications approved for NAFLD – a healthy diet and exercise are the standard of care – plenty of drugs are under development, as a recent article from Mitch Leslie in Science illustrates. As a reality check and benchmark, the NUSI study will address whether the low-tech intervention of altering diet can be effective.

Lab Land has delved into NAFLD and its increasing prevalence in previous posts. Plenty of correlational data shows that sugar intake is linked to NAFLD (a recent paper from the Framingham Heart Study), but Vos points out that there are no studies showing that reducing sugar is sufficient to drive improvement in the disease.

Diet is a challenge to examine in humans rigorously. In observational studies, investigators are always bumping up against the limits of memory and accurate reporting. In an interventional study with adults, it’s possible to provide them a completely defined menu for a short time in a closed environment, but that’s less practical for longer periods or with children.

The press release announcing the NUSI study says: half of the families will eat and drink what they normally do while the rest will be put on sugar-free meals and snacks, all of which will be provided for the participants and their families for eight weeks.

Miriam Vos, MD

I was curious about how this would work, especially for boys aged 11 to 16 (the participants in her study), so I asked Vos more about it for Lab Land.

“We try to provide them a diet that is otherwise similar to what the family is used to,” she says. “For example, if they’re accustomed to home-cooked meals, our team of nutritionists will work with them to find different recipes.” Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment