Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.

Optimal tissue regeneration in the periapical region is essential following a periapical surgery. Literature shows that augmenting the osseous defect with artificial bone substitutes, growth factors, or barrier membranes acts as critical factors influencing the healing following surgical intervention. For the regeneration of tissues following periapical surgery, an essential requisite is progenitor/stem cells. Few studies have shown that simple use of a membrane barrier and/or bone graft following surgery might not produce adequate tissue regeneration. Literature clearly shows that few substitutes are capable of generating progenitor/stem cells and induce the undifferentiated mesenchymal cells to differentiate. Hence, this review is intended to throw light on whether tissue regeneration with the aid of bone grafts coupled with a membrane barrier will suffice or is there a need for recruiting progenitor/stem cells.

Objective/Hypothesis: The apoliprotein E epsilon 4 (APOE4) variant is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and is associated with accelerated clinical disease. Increasing evidence suggests that the immune system plays a direct role in AD pathogenesis, and several studies show that APOE genotype alter inflammatory pathways. However, the mechanism by which APOE4 influences the immune system is unknown. Physical activity (PA) is thought to play a neuroprotective role in late-onset AD and represents a possible strategy to attenuate cognitive decline and amyloid beta deposition in APOE4 carriers. We hypothesize that PA counteracts the negative inflammatory effects mediated by APOE4 by promoting a protective microglial response. Methods: Mice with humanized APOE3 and APOE4 were crossed to 5xFAD transgenic mice, which carry mutant human APP and presenilin genes to drive amyloid pathology and neurodegeneration. The resultant transgenic mice (5xFAD;APOE4/4 and 5xFAD;APOE3/3) were subjected to a voluntary wheel running paradigm or stationary wheels for 4 months. We used immunohistochemical and ELISA-based techniques to evaluate microglia and neurons. The microglia disease-associated phenotype was assessed by Clec7a staining while homeostatic microglia markers were evaluated by P2ry12 staining. Neuronal numbers in cortical lamina V were evaluated by NeuN staining. Neurogenesis was evaluated by doublecortin staining. Results: We expect to see an increase in Clec7a and a decrease in P2ry12 staining on microglia surrounding beta amyloid plaques in 5xFAD;APOE4/4 mice subjected to running compared to mice housed with stationary wheels. In addition, we anticipate PA will ameliorate neuronal loss and promote neurogenesis in the subgranular zone of the dentate gyrus in the hippocampus. Conclusion/Potential Impact: The study will support the benefit of PA in attenuating the progression of late-onset AD in individuals with the APOE4 risk allele. The study will also elucidate the relationship between microglial responses, APOE genotype, and PA in AD.

During early testicular development, neonatal gonocytes transform into spermatogonial stem cells (SSC), and any untransformed gonocytes are thought to undergo apoptosis. In human cryptorchidism, persisting gonocytes may lead to seminoma. Using Bcl2-associated X knockout (BAXKO) mice, we investigated apoptosis in gonocyte development during mouse minipuberty. Testes from BAXKO, heterozygous (HET), and wild-type (WT) littermates were collected on postnatal days 1, 3, 6, and 9 (<i>n</i> = 6/group), labelled with antibodies against mouse vasa homologue (MVH, germ cell marker) or promyelocytic leukaemia zinc-factor (PLZF, SSC marker) and imaged for cell counting. Total germ cells/tubule, i.e., the number of germ cells on and off the basement membrane (BM), were counted using Image J followed by 2-way ANOVA analysis with Prism. Total PLZF+ germ cells/tubule, PLZF+ germ cells/tubule off BM, total MVH+ germ cells/tubule, and MVH+ germ cells off BM/tubule were significantly higher at day 9 in BAXKO compared to WT and HET mice (<i>p </i>< 0.01). In conclusion, knockout of BAX in mouse leads to gonocytes persisting at the centre of the tubules after minipuberty, which failed to migrate and transform into SSC, indicating the important role of apoptosis is to eliminate undifferentiated gonocytes during transformation. Failed apoptosis in gonocytes may be the cause of malignancy in humans with cryptorchidism.

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