Browsing by Author "Elmassry, Moamen M."

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    Ginger Polyphenols Reverse Molecular Signature of Amygdala Neuroimmune Signaling and Modulate Microbiome in Male Rats with Neuropathic Pain: Evidence for Microbiota–Gut–Brain Axis
    (2024) Shen, Chwan Li (TTUHSC); Santos, Julianna Maria (TTUHSC); Elmassry, Moamen M.; Bhakta, Viren (TTU); Driver, Zarek (TTU); Ji, Guangchen (TTUHSC); Yakhnitsa, Vadim (TTUHSC); Kiritoshi, Takaki (TTUHSC); Lovett, Jacob (TTUHSC); Hamood, Abdul Naji (TTUHSC); Sang, Shengmin; Neugebauer, Volker (TTUHSC)
    Emerging evidence shows that the gut microbiota plays an important role in neuropathic pain (NP) via the gut–brain axis. Male rats were divided into sham, spinal nerve ligation (SNL), SNL + 200 mg GEG/kg BW (GEG200), and SNL + 600 mg GEG/kg BW (GEG600) for 5 weeks. The dosages of 200 and 600 mg GEG/kg BW for rats correspond to 45 g and 135 g raw ginger for human daily consumption, respectively. Both GEG groups mitigated SNL-induced NP behavior. GEG-supplemented animals had a decreased abundance of Rikenella, Muribaculaceae, Clostridia UCG-014, Mucispirillum schaedleri, RF39, Acetatifactor, and Clostridia UCG-009, while they had an increased abundance of Flavonifactor, Hungatella, Anaerofustis stercorihominis, and Clostridium innocuum group. Relative to sham rats, Fos and Gadd45g genes were upregulated, while Igf1, Ccl2, Hadc2, Rtn4rl1, Nfkb2, Gpr84, Pik3cg, and Abcc8 genes were downregulated in SNL rats. Compared to the SNL group, the GEG200 group and GEG600 group had increases/decreases in 16 (10/6) genes and 11 (1/10) genes, respectively. GEG downregulated Fos and Gadd45g genes and upregulated Hdac2 genes in the amygdala. In summary, GEG alleviates NP by modulating the gut microbiome and reversing a molecular neuroimmune signature.
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    Pathogenesis of Pseudomonas aeruginosa during bacteremia: Influence of trauma
    (2020-05) Elmassry, Moamen M.; San Francisco, Michael J.; Hamood, Abdul N.; Rumbaugh, Kendra P.; Phillips, Caleb D.; Wakeman, Catherine A.
    The pathogenic Gram-negative bacterium, Pseudomonas aeruginosa, causes a significant burden on the healthcare system due to the numerous forms of infections it causes in different patient populations. Among these populations are trauma patients who may be immunocompromised, and thus become more susceptible to bloodstream infections. Although these infections are often fatal, the pathogenesis and metabolism of P. aeruginosa during bloodstream infections leading to sepsis is uninvestigated. Therefore, my work was focused on this critical matter. First, I used RNA-seq technology to investigate the global gene expression of P. aeruginosa while grown in whole blood from trauma patients in comparison to that of healthy volunteers. P. aeruginosa was found to differentially regulate the expression of 285 genes. Several of these were related to carbon metabolism and virulence factors. Among the genes that were significantly upregulated was the operon involved in malonate utilization. Malonate is one of the abundant organic acids in the human body and environment, and P. aeruginosa is known to be able to use it as a sole carbon source. Therefore, I have performed a series of experiments to characterize the effects of malonate utilization on the expression of virulence factors of P. aeruginosa. These experiments revealed that malonate utilization can reduce the production of numerous virulence factors in P. aeruginosa (e.g., LasA, LasB, rhamnolipids, and pyoverdine). On the other hand, malonate utilization enhanced the production of pyocyanin and catalase activity. Malonate utilization also caused the formation of suspended aggregates or biofilm-like structures rather than a surface-adhered biofilm. Use of malonate also increased the antibiotic sensitivity of P. aeruginosa to norfloxacin but increased its resistance to kanamycin. My results suggest the important role of malonate as a modulatory carbon source that affects many aspects of P. aeruginosa physiology including its virulence factors and antibiotic resistance. Future work in this direction will focus on the metabolism of P. aeruginosa in vivo to understand how malonate utilization contributes to P. aeruginosa virulence during systemic infections in trauma patients. Another critical aspect of sepsis in trauma patients, including burn patients that are more homogenous population (in terms of their injuries), is its diagnosis. Sepsis is associated with high mortality rates in these patients. Therefore, I investigated the metabolome of blood during sepsis to identify the changes in blood metabolites that could serve as sepsis markers. Furthermore, blood metabolome characterization would complement my previous studies to shed light on the environment that P. aeruginosa encounters during sepsis, which can enable us to understand how the host environment may influence the assailant pathogen. However, due to the unfeasibility to perform such experiments in human patients, I have used the established thermally injured murine model. The serum metabolome of thermally injured and P. aeruginosa infected mice contained 26 novel metabolites that could serve as biomarkers for early diagnosis of sepsis in burn patients. Taken together, my studies underscore the importance of interdisciplinary research to investigate the host environment and pathogen adaptation response and their interplay, which can develop new future therapies and diagnostic markers for systemic infections.