Dariimaa Ganbat, Bat-Erdene Jugder, Lkhamaa Ganbat, Miki Tomoeda, Erdenetsogt Dungubat, Yoshihisa Takahashi, Mori Ichiro, Takayuki Shiomi, and Yasuhiko Tomita. 1/19/2021. “The efficacy of Vitamin K, a member of Naphthoquinones in the treatment of cancer: a systematic review and meta-analysis.” Current Cancer Drug Targets. Publisher's VersionAbstract

Background: Redox dysregulation originating from metabolic alterations in cancer cells contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. Amongst them, Vitamin K (VitK), carries the potential against cancer stem cells, in addition to the rest of tumor mass.

Objectives: To assess the possible benefits and safety of VitK for cancer treatment using a systematic review and metaanalysis with a mixed-methods approach.

Methods: We performed a systematic search on several electronic databases for studies comparing VitK treatment with and without combination versus control groups. For quantitative studies, fully or partially reported clinical outcomes such as recurrence rates, survival, overall response, and adverse reactions were assessed. For qualitative studies, a narrative synthesis was accomplished.

Results: Our analysis suggested the clinical outcome of efficacy, the pooled hazard ratio for progression-free survival, and the pooled relative risk for overall survival, and overall response, were significantly higher in VitK therapy group compared to the placebo group (p<0.05). We did not observe any significant difference in the occurrence of adverse events between groups. Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid tumors resulted in 24.1% and 10% of clinical response, respectively.

Conclusion: VitK does not only exert antitumor effects against a wide range of tumor types, but it also has excellent synergism with other therapeutic agents.

Nady Braidy, Hayden Alicajic, David Pow, Jason Smith, Bat-Erdene Jugder, Bruce J. Brew, Joseph A. Nicolazzo, and Gilles J. Guillemin. 1/2021. “Potential Mechanism of Cellular Uptake of the Excitotoxin Quinolinic Acid in Primary Human Neurons.” Molecular Neurobiology, 58, 1, Pp. 34-54. Publisher's VersionAbstract
In Alzheimer’s disease (AD), excessive amounts of quinolinic acid (QUIN) accumulate within the brain parenchyma and dystrophic neurons. QUIN also regulates glutamate uptake into neurons, which may be due to modulation of Na+-dependent excitatory amino acid transporters (EAATs). To determine the biological relationships between QUIN and glutamate dysfunction, we first quantified the functionality and kinetics of [3H]QUIN uptake in primary human neurons using liquid scintillation. We then measured changes in the protein expression of the glutamate transporter EAAT3 and EAAT1b in primary neurons treated with QUIN and the EAAT inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (2,4-PDC) using western blotting and immunohistochemistry. Immunohistochemistry was further used to elucidate intracellular transport of exogenous QUIN and the lysosomal-associated membrane protein 2 (LAMP2). Structural insights into the binding between QUIN and EAAT3 were further investigated using molecular docking techniques. We report significant temperature-dependent high-affinity transport leading to neuronal uptake of [3H]QUIN with a Km of 42.2 μM, and a Vmax of 9.492 pmol/2 min/mg protein, comparable with the uptake of glutamate. We also found that QUIN increases expression of the EAAT3 monomer while decreasing the functional trimer. QUIN uptake into primary neurons was shown to involve EAAT3 as uptake was significantly attenuated following EAAT inhibition. We also demonstrated that QUIN increases the expression of aberrant EAAT1b protein in neurons further implicating QUIN-induced glutamate dysfunction. Furthermore, we demonstrated that QUIN is metabolised exclusively in lysosomes. The involvement of EAAT3 as a modulator for QUIN uptake was further confirmed using molecular docking. This study is the first to characterise a mechanism for QUIN uptake into primary human neurons involving EAAT3, opening potential targets to attenuate QUIN-induced excitotoxicity in neuroinflammatory diseases.
Audrey S. Vanhove, Bat-Erdene Jugder, Daniela Barraza, and Paula I. Watnick. 5/19/2020. “Methionine Availability in the Arthropod Intestine Is Elucidated through Identification of Vibrio cholerae Methionine Acquisition Systems.” Applied and Environmental Microbiology, 86, 11, Pp. e00371-20. Publisher's VersionAbstract
While only a subset of Vibrio cholerae strains are human diarrheal pathogens, all are aquatic organisms. In this environment, they often persist in close association with arthropods. In the intestinal lumen of the model arthropod Drosophila melanogaster, methionine and methionine sulfoxide decrease susceptibility to V. cholerae infection. In addition to its structural role in proteins, methionine participates in the methionine cycle, which carries out synthetic and regulatory methylation reactions. It is, therefore, essential for the growth of both animals and bacteria. Methionine is scarce in some environments, and the facile conversion of free methionine to methionine sulfoxide in oxidizing environments interferes with its utilization. To ensure an adequate supply of methionine, the genomes of most organisms encode multiple high-affinity uptake pathways for methionine as well as multiple methionine sulfoxide reductases, which reduce free and protein-associated methionine sulfoxide to methionine. To explore the role of methionine uptake and reduction in V. cholerae colonization of the arthropod intestine, we mutagenized the two high-affinity methionine transporters and five methionine sulfoxide reductases encoded in the V. cholerae genome. We show that MsrC is the sole methionine sulfoxide reductase active on free methionine sulfoxide. Furthermore, in the absence of methionine synthesis, high-affinity methionine uptake but not reduction is essential for V. cholerae colonization of the Drosophila intestine. These findings allow us to place a lower limit of 0.05 mM and an upper limit of 0.5 mM on the methionine concentration in the Drosophila intestine.
Bat-Erdene Jugder and Paula I. Watnick. 2/12/2020. “Vibrio cholerae Sheds Its Coat to Make Itself Comfortable in the Gut .” Cell Host & Microbe, 27, 2, Pp. 161-163. Publisher's Version
Paula I. Watnick and Bat-Erdene Jugder. 2/2020. “Microbial Control of Intestinal Homeostasis via Enteroendocrine Cell Innate Immune Signaling.” Trends in Microbiology, 28, 2, Pp. 141-149. Publisher's VersionAbstract
A community of commensal microbes, known as the intestinal microbiota, resides within the gastrointestinal tract of animals and plays a role in maintenance of host metabolic homeostasis and resistance to pathogen invasion. Enteroendocrine cells, which are relatively rare in the intestinal epithelium, have evolved to sense and respond to these commensal microbes. Specifically, they express G-protein-coupled receptors and functional innate immune signaling pathways that recognize products of microbial metabolism and microbe-associated molecular patterns, respectively. Here we review recent evidence from Drosophila melanogaster that microbial cues recruit antimicrobial, mechanical, and metabolic branches of the enteroendocrine innate immune system and argue that this response may play a role not only in maintaining host metabolic homeostasis but also in intestinal resistance to invasion by bacterial, viral, and parasitic pathogens.
Nady Braidy, Martin Zarka, Bat-Erdene Jugder, Jeffrey Welch, Tharusha Jayasena, Daniel K. Y. Chan, Perminder Sachdev, and Wallace Bridge. 8/8/2019. “The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes.” Frontiers in Aging Neuroscience, 11, 177. Publisher's Version
Bat-Erdene Jugder, Karl AP Payne, Karl Fisher, Susanne Bohl, Helene Lebhar, Mike Manefield, Matthew Lee, David Leys, and Christopher P Marquis. 1/2018. “Heterologous production and purification of a functional chloroform reductive dehalogenase.” ACS chemical biology, 13, 3, Pp. 548-552. Publisher's Version
Bat‐Erdene Jugder, Susanne Bohl, Helene Lebhar, Robert D Healey, Mike Manefield, Christopher P Marquis, and Matthew Lee. 11/2017. “A bacterial chloroform reductive dehalogenase: purification and biochemical characterization.” Microbial biotechnology, 10, 6, Pp. 1640-1648. Publisher's Version
Nady Braidy, Anne Poljak, Chris Marjo, Helen Rutlidge, Anne Rich, Bat-Erdene Jugder, Tharusha Jayasena, Nibaldo C Inestrosa, and Perminder S Sachdev. 3/29/2017. “Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus.” Frontiers in aging neuroscience, 9, 66. Publisher's Version
Nady Braidy, Helene Rossez, Chai K Lim, Bat-Erdene Jugder, Bruce J Brew, and Gilles J Guillemin. 11/1/2016. “Characterization of the kynurenine pathway in CD8+ human primary monocyte-derived dendritic cells.” Neurotoxicity research, 30, 4, Pp. 620-632. Publisher's Version
Bat‐Erdene Jugder, Haluk Ertan, Yie Kuan Wong, Nady Braidy, Michael Manefield, Christopher P Marquis, and Matthew Lee. 10/1/2016. “Genomic, transcriptomic and proteomic analyses of Dehalobacter UNSWDHB in response to chloroform.” Environmental microbiology reports, 8, 5, Pp. 814-824. Publisher's Version
Bat-Erdene Jugder, Jeffrey Welch, Nady Braidy, and Christopher P Marquis. 7/26/2016. “Construction and use of a Cupriavidus necator H16 soluble hydrogenase promoter (PSH) fusion to gfp (green fluorescent protein).” PeerJ, 4, Pp. e2269. Publisher's Version
Nady Braidy, Bat-Erdene Jugder, Anne Poljak, Tharusha Jayasena, Hussein Mansour, Seyed Mohammad Nabavi, Perminder Sachdev, and Ross Grant. 7/1/2016. “Resveratrol as a potential therapeutic candidate for the treatment and management of Alzheimer’s disease.” Current topics in medicinal chemistry, 16, 17, Pp. 1951-1960. Publisher's Version
Bat-Erdene Jugder, Helene Lebhar, Kondo-Francois Aguey-Zinsou, and Christopher P Marquis. 3/22/2016. “Production and purification of a soluble hydrogenase from Ralstonia eutropha H16 for potential hydrogen fuel cell applications.” MethodsX, 3, Pp. 242-250. Publisher's Version
Bat-Erdene Jugder, Haluk Ertan, Susanne Bohl, Matthew Lee, Christopher P Marquis, and Michael Manefield. 3/1/2016. “Organohalide respiring bacteria and reductive dehalogenases: key tools in organohalide bioremediation.” Frontiers in microbiology, 7, 249. Publisher's Version
Bat-Erdene Jugder, Haluk Ertan, Matthew Lee, Michael Manefield, and Christopher P Marquis. 10/1/2015. “Reductive dehalogenases come of age in biological destruction of organohalides.” Trends in biotechnology, 33, 10, Pp. 595-610. Publisher's Version
Bat-Erdene Jugder, Zhiliang Chen, Darren Tan Tek Ping, Helene Lebhar, Jeffrey Welch, and Christopher P Marquis. 3/25/2015. “An analysis of the changes in soluble hydrogenase and global gene expression in Cupriavidus necator (Ralstonia eutropha) H16 grown in heterotrophic diauxic batch culture.” Microbial cell factories, 14, 1, Pp. 42. Publisher's Version
Bat-Erdene Jugder, Jeffrey Welch, Kondo-Francois Aguey-Zinsou, and Christopher P Marquis. 1/28/2013. “Fundamentals and electrochemical applications of [Ni–Fe]-uptake hydrogenases.” RSC Advances, 3, 22, Pp. 8142-8159. Publisher's Version