Invasive pulmonary aspergillosis is a frequent complication in immunocompromised individuals, and it continues to be an important cause of mortality in patients undergoing hematopoietic stem cell transplantation. In addition to antifungal therapy used for mycoses, immune-modulatory molecules such as cytokines and chemokines can modify the host immune response and exhibit a promising form of antimicrobial therapeutics to combat invasive fungal diseases. Cytokine and chemokine profiles may also be applied as biomarkers during fungal infections and clinical research has demonstrated different activation patterns of cytokines in invasive mycoses such as aspergillosis. In this review, we summarize different aspects of cytokines that have been described to date and provide possible future directions in research on invasive pulmonary aspergillosis following hematopoietic stem cell transplantation. These findings suggest that cytokines and chemokines may serve as useful biomarkers to improve diagnosis and monitoring of infection.

Metabolic syndrome (MetS) is known to be related to mild cognitive impairment (MCI). A prognostic biomarker for the MCI condition in these patients has not been thoroughly determined.  A neutrophil-lymphocyte ratio (NLR) has been widely used as a biomarker for the progression of cancers and cardiovascular diseases.  However, its association with the MCI condition in patients with MetS is not known. The present study aimed to investigate the correlation between NLR and cognitive function in patients with MetS.  A total of sixty patients with MetS (45-65 years old) were enrolled in the present study, and their metabolic parameters, including plasma levels of glucose, insulin, lipid profiles, inflammatory markers, and the complete blood count, were determined.  The NLR level was calculated by the ratio of neutrophils to lymphocytes derived from the complete blood count.  The Montreal Cognitive Assessment (MoCA) test was used to determine the cognitive performance in patients with MetS. Most patients with MetS have the possibility of an MCI condition.  Moreover, glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), and NLR were negatively correlated with the MoCA scores of these patients.  Interestingly, NLR was the strongest independent factor which correlated with the MoCA score. Collectively, poor glycemic control and increased NLR levels may be used as possible predictors for poorer cognitive performance outcomes in patients with MetS.   Keywords: Metabolic syndrome; Mild cognitive impairment; Neutrophil-lymphocyte ratio; Prognostic marker; Montreal cognitive assessment   Citation: Pipatpiboon, N., Sripetchwandee, J., Sa-nguanmoo, P., Tachaudomdach, C., Jomgeow, T., Phrommintikul, A., Chattipakorn, N., and Chattipakorn, S.C. 2022. Neutrophil-Lymphocyte Ratio (NLR) is positively associated with impaired cognitive performance in patients with metabolic syndrome. CMU J. Nat. Sci. 21(1): e2022013.

Background: Our studies suggest that iron‐overloaded rats developed neurotoxicity and cognitive impairment (1,2). An increase in brain mitochondrial fission and brain mitophagy have been considered as one of underlying mechanisms in brain with iron‐overloaded condition (3,4). Hence, a pharmacological intervention focused on preventing brain mitochondrial pathologies is required. The mitochondrial fission inhibitor, Mdivi‐1, has recently gained attention because of its beneficial effects on several neuropathological conditions including traumatic brain injury and intracerebral hemorrhage (5,6). However, the effectiveness of Mdivi‐1, particularly regarding brain mitochondrial parameters and cognitive function in iron‐overloaded condition, has not been investigated.Methods: Twenty‐four male adult Wistar rats were divided into 2 groups to receive an intraperitoneal injection with 10% dextrose in normal saline solution (NSS) as a control group (n = 6) or 100 mg/kg iron dextran as an iron‐overloaded group (n = 18). After 4 weeks of injection, the iron‐overloaded group was subdivided into 3 subgroups (n = 6/subgroup) to subcutaneously receive pharmacological interventions either 1) vehicle (10% DMSO in NSS), 2) deferoxamine (25 mg/kg), or 3) Mdivi‐1 (2 mg/kg). The control rats were also given a vehicle. All rats were received the assigned treatment for further 2 weeks. Behavioral tests including open field test (locomotor activities) and the Morris water maze test (spatial memory test) were evaluated. At the end of experiments, rats were euthanized, and serum samples were collected to assess serum iron level. Furthermore, brain tissues were preserved for the assessment of blood‐brain tight junction protein, brain iron level, and the protein expression related to brain mitochondrial fission and brain mitophagy.Results: Iron dextran‐injected rats demonstrated an increase in serum/brain iron levels, called as “iron‐overloaded condition”, blood‐brain barrier disruption, and increased brain mitochondrial fission and brain mitophagy, resulting in a decline in spatial memory. The administration of deferoxamine alleviated brain pathologies and partially mitigated the impaired spatial memory test in iron‐treated rats. Interestingly, the Mdivi‐1 exhibited greater neuroprotective effects than deferoxamine by attenuating brain mitophagy and restoring spatial memory (Figure 1).Conclusion: Mdivi‐1 potentially exerted neuroprotective effects and cognitive restoration in iron‐overloaded rats, suggesting a novel therapeutic strategy using mitochondrial fission inhibitor in the brain following iron‐overloaded condition.