Nhu Nguyen

All Publications

• Development and validation of a rabbit model of Pseudomonas aeruginosa hyperdynamic septic shock for preclinical drug development. Antimicrobial agents and chemotherapy Tran, N. D., Nguyen, N. T., Vu, T. T., Diep, P. -., Villescas, N. N., Nguyen, N. N., Sato, K. M., Weiss, W. J., Doan, T. N., Diep, B. A. 2026: e0193625

  Abstract

  Translating preclinical findings into clinical success remains a major barrier in the development of antimicrobials targeting Pseudomonas aeruginosa, particularly for severe infections such as sepsis and septic shock. Rodent models frequently fail to predict therapeutic efficacy in clinical sepsis. To address this gap, we developed and validated a rabbit model of hyperdynamic septic shock incorporating intensive care unit (ICU)-style monitoring and supportive care to better reflect human clinical practice. Rabbits challenged intravenously with P. aeruginosa progressed predictably from hyperdynamic circulation to hypodynamic shock, characterized by progressive metabolic acidosis, leukocyte dysregulation, and acute myocardial injury. A sustained 20% decline in mean arterial pressure reliably marked the onset of cardiovascular decompensation and was prospectively applied in follow-on studies as a predefined hemodynamic trigger for initiating therapeutic interventions. Despite pharmacokinetic studies showing that ciprofloxacin 30 mg/kg infused over 1 h every 8 h achieved human-equivalent exposures and exceeded the AUC0-24h/MIC ≥ 125 efficacy threshold, ciprofloxacin monotherapy improved survival compared to placebo but failed to prevent progression to fatal shock. In contrast, the combination of ciprofloxacin and protocolized supportive care-based on the clinical "VIP" strategy (ventilation, infusion, and pressor)-rescued 75% of animals from lethal septic shock compared with VIP plus placebo, while also stabilizing physiological parameters and markedly reducing bacterial burdens. Together, these findings underscore the importance of VIP supportive care for maintaining hemodynamic stability and establish a clinically relevant platform for evaluating antimicrobial therapies.

  View details for DOI 10.1128/aac.01936-25

  View details for PubMedID 42295241

• Transcranial microtesla magnetic fields suppress neuroinflammation and neuronal oxidative stress burden. iScience Nguyen, N., Brady, N. R., Timblin, G. A., Tharp, K. M., Gurfein, B. T. 2026; 29 (1): 114425

  Abstract

  Neuroinflammation is a major driver of neurodegenerative and psychiatric disease, yet current therapies have limited brain penetration and efficacy. We investigated microtesla magnetic therapy (MMT), a brief transcranial exposure to time-varied electromagnetic fields (TV-EMFs), as a noninvasive approach to modulate neuroimmune inflammation. In human peripheral blood mononuclear cells, MMT suppressed lipopolysaccharide (LPS)-induced TNFα and IL-1β release and reduced NF-κB activation in monocyte and macrophage lines. In rats with intracerebral LPS injection, a model of progressive neuroinflammation, repeated head-localized MMT markedly decreased microgliosis, astrogliosis, and lesion size. In a neuron-immune cell model, MMT reduced cytokine-driven and paraquat-induced oxidative stress, producing both indirect and direct neuroprotection lasting up to 48 h. Collectively, these findings validate transcranial MMT as a promising, noninvasive biophysical therapy for neuroinflammatory conditions. Both acute and repetitive TV-EMF protocols delivered robust anti-inflammatory, antioxidant, and neuroprotective effects, demonstrating the therapeutic potential of precisely modulated EMFs to safely manage neuroinflammation.

  View details for DOI 10.1016/j.isci.2025.114425

  View details for PubMedID 41550771

  View details for PubMedCentralID PMC12803945

• Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against Staphylococcus aureus-induced acute circulatory failure in a mechanically ventilated rabbit model of hyperdynamic septic shock. Frontiers in immunology Nguyen, N. T., Doan, T. N., Sato, K., Tkaczyk, C., Sellman, B. R., Diep, B. A. 2023; 14: 1260627

  Abstract

  Patients with septic shock caused by Staphylococcus aureus have mortality rates exceeding 50%, despite appropriate antibiotic therapy. Our objectives were to establish a rabbit model of S. aureus septic shock and to determine whether a novel immunotherapy can prevent or halt its natural disease progression.Anesthetized rabbits were ventilated with lung-protective low-tidal volume, instrumented for advanced hemodynamic monitoring, and characterized for longitudinal changes in acute myocardial dysfunction by echocardiography and sepsis-associated biomarkers after S. aureus intravenous challenge. To demonstrate the potential utility of this hyperdynamic septic shock model for preclinical drug development, rabbits were randomized for prophylaxis with anti-Hla/Luk/ClfA monoclonal antibody combination that neutralizes alpha-hemolysin (Hla), the bicomponent pore-forming leukocidins (Luk) including Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysin, and clumping factor A (ClfA), or an irrelevant isotype-matched control IgG (c-IgG), and then challenged with S. aureus.Rabbits challenged with S. aureus, but not those with saline, developed a hyperdynamic state of septic shock characterized by elevated cardiac output (CO), increased stroke volume (SV) and reduced systemic vascular resistance (SVR), which was followed by a lethal hypodynamic state characterized by rapid decline in mean arterial pressure (MAP), increased central venous pressure, reduced CO, reduced SV, elevated SVR, and reduced left-ventricular ejection fraction, thereby reproducing the hallmark clinical features of human staphylococcal septic shock. In this model, rabbits pretreated with anti-Hla/Luk/ClfA mAb combination had 69% reduction in mortality when compared to those pretreated with c-IgG (P<0.001). USA300-induced acute circulatory failure-defined as >70% decreased in MAP from pre-infection baseline-occurred in only 20% (2/10) of rabbits pretreated with anti-Hla/Luk/ClfA mAb combination compared to 100% (9/9) of those pretreated with c-IgG. Prophylaxis with anti-Hla/Luk/ClfA mAb combination halted progression to lethal hypodynamic shock, as evidenced by significant protection against the development of hyperlactatemia, hypocapnia, hyperkalemia, leukopenia, neutropenia, monocytopenia, lymphopenia, as well as biomarkers associated with acute myocardial injury.These results demonstrate the potential utility of a mechanically ventilated rabbit model that reproduced hallmark clinical features of hyperdynamic septic shock and the translational potential of immunotherapy targeting S. aureus virulence factors for the prevention of staphylococcal septic shock.

  View details for DOI 10.3389/fimmu.2023.1260627

  View details for PubMedID 37781371

  View details for PubMedCentralID PMC10541218

• Pseudomonas aeruginosa Ventilator-Associated Pneumonia Rabbit Model for Preclinical Drug Development. Antimicrobial agents and chemotherapy Nguyen, N. T., Gras, E., Tran, N. D., Nguyen, N. N., Lam, H. T., Weiss, W. J., Doan, T. N., Diep, B. A. 2021; 65 (7): e0272420

  Abstract

  Development and validation of large animal models of Pseudomonas aeruginosa ventilator-associated pneumonia are needed for testing new drug candidates in a manner that mimics how they will be used clinically. We developed a new model in which rabbits were ventilated with low tidal volume and challenged with P. aeruginosa to recapitulate hallmark clinical features of acute respiratory distress syndrome (ARDS): acute lung injury and inflammation, progressive decrease in arterial oxygen partial pressure to fractional inspired oxygen PaO2:FiO2, leukopenia, neutropenia, thrombocytopenia, hyperlactatemia, severe hypotension, bacterial dissemination from lung to other organs, multiorgan dysfunction, and ultimately death. We evaluated the predictive power of this rabbit model for antibiotic efficacy testing by determining whether a humanized dosing regimen of meropenem, a potent antipseudomonal β-lactam antibiotic, when administered with or without intensive care unit (ICU)-supportive care (fluid challenge and norepinephrine), could halt or reverse natural disease progression. Our humanized meropenem dosing regimen produced a plasma concentration-time profile in the rabbit model similar to those reported in patients with ventilator-associated bacterial pneumonia. In this rabbit model, treatment with humanized meropenem and ICU-supportive care achieved the highest level of survival, halted the worsening of ARDS biomarkers, and reversed lethal hypotension, although treatment with humanized meropenem alone also conferred some protection compared to treatment with placebo (saline) alone or placebo plus ICU-supportive care. In conclusion, this rabbit model could help predict whether an antibiotic will be efficacious for the treatment of human ventilator-associated pneumonia.

  View details for DOI 10.1128/AAC.02724-20

  View details for PubMedID 33972247

  View details for PubMedCentralID PMC8218622

• Novel mutation in EFCAB7 alters expression and interaction of Ellis-van Creveld ciliary proteins. Congenital anomalies Nguyen, T. Q., Doan, N. M., Trinh, H. T., Mizuguchi, M. 2019; 59 (2): 49-50

  View details for DOI 10.1111/cga.12291

  View details for PubMedID 29845660

• Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome. Congenital anomalies Nguyen, T. Q., Saitoh, M., Trinh, H. T., Doan, N. M., Mizuno, Y., Seki, M., Sato, Y., Ogawa, S., Mizuguchi, M. 2016; 56 (5): 209-16

  Abstract

  Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. To obtain further insight into the genetics of EvC, we screened EVC/EVC2 mutations in eight Vietnamese EvC patients. All the patients had a congenital heart defect with atypical oral and/or skeletal abnormalities. One had compound heterozygous EVC2 mutations: a novel mutation c.769G > T-p.E177X in exon 6 inherited from father and another previously reported c.2476C > T-p.R826X mutation in exon 14 inherited from mother. The EVC2 mRNA expression level was significantly lower in the patient and her parents compared to controls. Another case had a novel heterozygous EVC mutation (c.1717C > G-p.S572X) in exon 12, inherited from his father. Of note, the mother without any EVC mutation on Sanger sequencing showed a lower expression level of EVC mRNA compared with controls. SNP array analysis revealed that the patient and mother had a heterozygous 16.4 kb deletion in EVC. This patient also had a heterozygous novel variant in exon 9 of EFCAB7 (c.1171 T > C-p.Y391H), inherited from his father. The atypical cardiac phenotype of this patient and the father suggested that EFCAB7 may modify the phenotype by interacting with EVC. In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders.

  View details for DOI 10.1111/cga.12155

  View details for PubMedID 26748586