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Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

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The immune system is responsible not only for protection against foreign invaders (e.g., viruses and bacteria) but also against abnormal cell growth (e.g., cancer). Although the initiating causes of cancer are wide-ranging, one universal characteristic common to all is that healthy cells mutate in ways that dysregulate their growth and survival. Unchecked, these cells may grow and mutate uncontrollably, making immunosurveillance vital to maintaining a healthy organism. T cells recognize foreign antigens via their T Cell Receptors (TCRs). A sampling of all proteins made by the cell is presented to T cells in the context of Major Histocompatibility Complexes (MHCs) present on all nucleated cells. A successful interaction between a T cell and an MHC bearing a non-self peptide will initiate an immune response including TCR signaling and proliferation. Cells that avoid this recognition can grow into tumors. Interestingly, these tumors have been observed to exist in acidic microenvironments. One concern is that the acidic nature of the tumor microenvironment could negatively impact the interaction between the T cell and MHC molecule thereby reducing the efficacy of an immune response. We used Jurkat T cells as a model T cell line to evaluate the survival and immune signaling of T cells under low pH environments. We observed less total phosphorylation in the acidic conditions, however, the relative increase in phosphorylation above background was much greater under acidic conditions. These results indicate a qualitative change in T cells activation signals when exposed to an acidic environment.

Glutamate is our body’s primary excitatory neurotransmitter and plays a critical role in neuronal signaling allowing for the perception of the external world and the formation of memories. In excess, glutamate behaves as an excitotoxin that can induce neuronal apoptosis. Evidence exists that during head trauma neuronal cells can be exposed to supraphysiological concentrationsof glutamate causing damage or cell death. Both GABA receptor agonists and voltage-gated calcium channel blockers have been shown to have an attenuating effect on glutamatergic excitotoxicity via antagonistic signaling and inhibition of glutamate release.Phenibut, a widely available gabapentinoid, possesses both mechanisms of action, making it an appealing candidate as a therapeutic in the treatment of traumatic brain injury.

Green tea has a high abundance of catechins and other antioxidants found organically within its composition. In recent studies, a polyphenolic catechin, referred to as EGCG, has shown the potential to promote advancements in the development of non-harmful cancer treatments. Several experimental questions were explored regarding EGCG, including the concentration of EGCG present in commercial green teas, its anticancer potency, and EGCG’s potential contributions to cell cycle arrest. Briefly, a green tea extract was prepared utilizing ground green tea leaves and a polar extraction method. The fluorescent properties of EGCG were exploited to quantitate its concentration in green tea preparations in comparison to a purified EGCG standard. The anticancer potency of EGCG was then assessed by exposing HeLa (cancer cells) and MRC-5 (primary) cells to green tea extract- containing the EGCG component- for 24 hrs. The cells were evaluated for viability, suggesting that higher concentrations of extract exerted specificity toward cancer cells over the control model. Lastly, HCT-116 cancer cells were evaluated for cell cycle arrest following drug treatment. Results indicated that green tea extract imposed a cytotoxic effect selective to cancer cells while avoiding cytotoxicity to a primary cell model. In addition, treated cancer cells experienced an increase in the cell population at the G1 phase, indicating a halt in the cell cycle. This hypothesis was supported by an observed decrease in cell population in the S phase. These results show the potential for green tea extracts containing EGCG to be potential components in cancer therapeutics and/or preventatives.

About 1.5 million Americans suffer from Rheumatoid Arthritis (RA), an autoimmune, chronic inflammatory disease with no cure. This is a condition in which the immune system mistakenly attacks healthy cells, leaving the body in a constant state of inflammation. A major characteristic of RA is unresolved inflammation specifically in the joints of the hands, wrists, and knees. People who have RA suffer from a lot of pain, experience bone, and joint deformity, and have a loss of function in the targeted areas. In patients with RA, the immune system is not working properly, and the immune responses are unregulated. Due to being an autoimmune disorder, our B cells are presenting healthy cells with autoantigens that trigger multiple signaling pathways that lead to the release of cytokines. A primary cytokine, IL-6, plays a role in the pathogenesis of RA due to its pro-inflammatory effects. IL-6 causes the release of acute phase proteins which cause fevers, iron deficiency, fatigue, fat and muscle loss, anorexia, and weakness. One way to treat RA is to target the inflammation directly by interrupting cytokine release. In this work, the effect of CBD was evaluated to determine if its application has the potential to decrease IL-6 expression/release by inflamed cells. Macrophages derived from THP-1 Cells cultured with PMA were treated with LPS to model inflammation in vitro and the expression of IL-6 was determined by ELISA to correlate in a dose-dependent manner to LPS.