July 2017 Journal Club

[SLCpod]

I apologize for not posting journals the past few months. I have been very busy with moving, graduation, and starting residency.

Journal club overview:
- An article will be selected and posted each month. Please PM me an article you are interested in and I will select one. Please keep them as recent as possible.
- We will discuss how we can use what we learned from the selected article in practice and perhaps share some clinical experiences (remember not to disclose specific patient information)

This is open to DPM's, students and pre-pods!! All are invited.

This article was provided by @Weirdy . That means @Weirdy should give a good review and breakdown of the article.



To go along with wound healing, I suggest that the students read this article:

Probe-to-Bone Test for Diagnosing Diabetic Foot Osteomyelitis



Recently, I attended a wound care conference that had great insight about how to treat non-healing wounds and diabetic wounds. The information was very insightful. Perhaps @diabeticfootdr give us some additional articles that students should read in preparation for upcoming clerkships.

**August Topic: Calcaneal fractures**

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[Weirdy]

Gallagher et al, 2015
Assess role of histone methylation in bone marrow stem/progenitor cells in programming macrophages toward a proinflammatory phenotype.

Found repressive histone methylation mark H3K27me3 --> decreased at promotor of the IL-12 gene was passed down to wound macrophages in diet-induced obese models. Negatively impact wound repair (induce uncontrolled inflammation).

In diabetic conditions the demethylase (Jmmd3) drives IL-12 production. Methyl group on = inhibit inflammation phenotype. Demethyl = induce inflammation phenotype.
IL-12 production can be controlled by inhibiting Jmjd3 (a H3K27 demethylase).

Possible applications: Use histone methylation epigenetically to control expression of inflammatory phenotype in macrophages. Decrease inflammation, help wounds heal better. Thought it was interesting because targeting immune system at molecular level instead of targeting diabetes control.

More details
Methods/Research Design:
Mouse model and human tissue used.
Normal diet + high fat diet mice with induced wounds (4mm punch biopsy). Wounds assessed by measurement. Quantified by percentage of original wound over time.
Human macrophage isolated from nondiabetic + Type II diabetic patients following amputation. Tissue obtained immediately after amputation. Comorbid conditions: CHF, coronary artery disease, renal, smoking status, obesity.
Results
Human wounds, macrophages in mounts have distinct proinflammatory phenotype
Delayed wound healing in diet induced obese mice associated with increased proinflammatory macrophages
Decreased histone lysine trimethylation (H3K27me3) at promoter region of proinflammatory macrophage gene IL-12.

EDIT: How plausible is it to control histone methylation or gene inhibition for clinical use? I do not know enough to get there.