Publications by authors named "Antonio L Teixeira"

271 Publications

Multidimensional Approach Assessing the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy.

Front Neurol 2021 5;12:690847. Epub 2021 Aug 5.

Department of Translational Medicine, University of Campinas, Campinas, Brazil.

We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the gene; (ii) quantification of the transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364C in the gene, regardless of the presence of FS (adjusted = 9.62e-11 and 5.14e-07, respectively). We found no difference between transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls ( > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls ( = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the gene.
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http://dx.doi.org/10.3389/fneur.2021.690847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375265PMC
August 2021

Revisiting Apathy in Alzheimer's Disease: From Conceptualization to Therapeutic Approaches.

Behav Neurol 2021 3;2021:6319826. Epub 2021 Aug 3.

Department of Psychiatry & Behavioral Health, Stony Brook University, Stony Brook, New York, USA.

Apathy is a neurobehavioral syndrome characterized by impaired motivation for goal-directed behaviors and cognitive activity, alongside blunted affect. Apathy is a common neuropsychiatric syndrome in Alzheimer's disease (AD), with a 5-year prevalence over 70%. Apathy also serves as a prognostic indicator, correlating with the progression of AD. Despite advances in its conceptualization and understanding of its neural basis, there is very limited empirical evidence to support the available strategies for the treatment of apathy in AD. Given its complex pathophysiology, including distinct substrates for different apathy dimensions (affective, cognitive, and behavioral), it is unlikely that a single pharmacological or nonpharmacological strategy will be effective for all cases of apathy in AD. High-quality evidence research is needed to better understand the role of specific strategies aiming at a personalized approach.
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http://dx.doi.org/10.1155/2021/6319826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356015PMC
August 2021

Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain.

Mol Psychiatry 2021 Aug 12. Epub 2021 Aug 12.

Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.
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http://dx.doi.org/10.1038/s41380-021-01259-yDOI Listing
August 2021

Sydenham's chorea: from pathophysiology to therapeutics.

Expert Rev Neurother 2021 Aug 18;21(8):913-922. Epub 2021 Aug 18.

Department of Neurology, Johns Hopkins Medicine and Kennedy Krieger Institute, Baltimore, MD, USA.

Sydenham's chorea is an autoimmune chorea emerging after a group A beta-hemolytic streptococcal (GABHS) infection, i.e. a rheumatic chorea with or without the presence of carditis or arthritis. The disorder, defined by the presence of chorea, is also associated with cognitive and behavioral symptoms, including emotional lability, anxiety, depressive and obsessive-compulsive symptoms. The authors review the pathophysiology, clinical characteristics, and available evidence on therapeutic strategies, the latter including the secondary prevention of GABHS infections, reduction of chorea, and immune modulation. Sydenham's chorea has been regarded as a model for pediatric autoimmune neuropsychiatric disorders, however, the field is marked by conflicting results and controversies. Regarding therapeutics, there are limited high-quality interventional studies and the selection of treatment strategy often relies on the clinician's experience. A serial treatment algorithm is presented based upon the severity of clinical presentation and response to symptomatic pharmacotherapy.
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http://dx.doi.org/10.1080/14737175.2021.1965883DOI Listing
August 2021

Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology.

Epilepsia 2021 Jul 31. Epub 2021 Jul 31.

University of Campinas, Campinas, Brazil.

Objective: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes.

Methods: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array.

Results: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures.

Significance: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.
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http://dx.doi.org/10.1111/epi.17023DOI Listing
July 2021

Unveiling the Metabolic Profile of First-Episode Drug-Naïve Schizophrenia Patients: Baseline Characteristics of a Longitudinal Study Among Han Chinese.

Front Psychiatry 2021 9;12:702720. Epub 2021 Jul 9.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Metabolic and other medical conditions are frequently comorbid with schizophrenia. As they might be the side-effects of antipsychotic treatment, studying first-episode drug-naïve schizophrenia (FDSZ) provides a unique opportunity to investigate a direct pathogenic link between metabolic changes and schizophrenia. Here, we presented the methods and baseline unique metabolic profile of FDSZ patients without medical comorbidities unveiling subthreshold indices of metabolic disturbances. Drug-naïve individuals diagnosed with schizophrenia but without any previous medical conditions were invited to participate in the study. Participants were submitted to structured psychiatric and cognitive assessments, laboratory and neuroimaging tests. Subjects will be followed after antipsychotic treatment at 6, 24 and 48 weeks. During an 8-month-period, out of 103 patients presenting with first episode psychosis, 67 subjects (43.3% men, 56.7% women) were enrolled in the study. They had a mean ± SD age of 32.1 ± 8.7 years, with a mean BMI of 21.1 kg/m and 11.3 ± 3.6 years of schooling. Less than 1/3 reported a family history of mental illness. Upon laboratory assessment, 10.4%, 7.5%, and 11.9% of patients were identified with hyperhomocysteinemia, hypertriglyceridemia and hyperprolactinemia, respectively, with percentages of women relatively higher than men except for hypertriglyceridemia. First episode schizophrenia patients, especially women, present subclinical metabolic abnormalities, independent of antipsychotic treatment.
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http://dx.doi.org/10.3389/fpsyt.2021.702720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298856PMC
July 2021

Cannabinoid receptor gene polymorphisms and cognitive performance in patients with schizophrenia and controls.

Braz J Psychiatry 2021 Jun 23. Epub 2021 Jun 23.

Programa Interdisciplinar de Pós-Graduação em Neurociências, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Objective: To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia.

Methods: In this genetic association case-control study, cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS).

Results: We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving.

Conclusion: Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.
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http://dx.doi.org/10.1590/1516-4446-2020-1650DOI Listing
June 2021

Inflammatory and oxidative biomarkers as determinants of functional capacity in patients with COPD assessed by 6-min walk test-derived outcomes.

Exp Gerontol 2021 09 21;152:111456. Epub 2021 Jun 21.

Laboratório de Inflamação e Metabolismo - LIM - CIPq/Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Sociedade Brasileira de Fisiologia, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil. Electronic address:

Introduction: Reduction in functional capacity is a negative clinical outcome of chronic obstructive pulmonary disease (COPD). Studies have shown association between inflammatory and oxidative stress biomarkers and functional capacity. However, it is unclear whether these biomarkers are associated with outcomes of functional capacity. Therefore, the aim of this study was to evaluate whether plasma biomarkers of inflammation and oxidative stress are predictors of the 6-min walking test (6MWT)-derived outcomes.

Methods: Twenty COPD patients were assessed on three consecutive days with different clinical measures, including functional capacity, and blood sampling. Plasma concentrations of IL-6, IL-8, TNF-ɑ, IL-10 and soluble TNF-ɑ receptors (sTNFR1 and sTNFR2) were determined by immunoassays. Oxidative stress was evaluated by determining lipid peroxidation products based on the enzymatic activity of superoxide dismutase (SOD) and catalase, and total antioxidant capacity of plasma. Functional capacity was assessed considering the six-minute walking distance (6MWD) and the estimate of six-minute walking work (6MWW). The association between biomarkers (i.e. inflammation and oxidative stress) and functional exercise capacity was investigated through the Pearson's correlation coefficient. To identify the determinants of the 6MWT, multiple linear stepwise regression analyses were performed with adjustment for age, sex and GOLD classification.

Results: Patients were predominantly male (65%), with mean age of 64 years and moderate airflow obstruction and impaired functional capacity. There were positive correlations between SOD activity and 6MWD (r = 0.520; p = 0.02) and 6MWW (r = 0.554; p = 0.01), as well as a negative correlation between sTNF-R1 and 6MWD (r = -0.437; p = 0.05). SOD was an independent determinant of the functional capacity, explaining 23% of the variability of 6MWD (p = 0.019) and 27% of the variability of 6MWW (p = 0.011). sTNF-R1 levels were associated with 6MWD and, together with SOD explained 40% of variability in 6MWD (p = 0.005).

Conclusion: SOD activity was an independent determinant of performance in the 6MWT, and together with sTNFR1 explained 40% of the variations in walking distance in COPD patients. SOD activity and sTNFR1 levels might be seen as potential biomarkers of the functional capacity in patients with COPD.
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http://dx.doi.org/10.1016/j.exger.2021.111456DOI Listing
September 2021

Correlations between peripheral levels of inflammatory mediators and frontolimbic structures in bipolar disorder: an exploratory analysis.

CNS Spectr 2021 Jun 14:1-6. Epub 2021 Jun 14.

Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center, Houston, Texas, USA.

Background: Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD.

Methods: Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer.

Results: Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = -0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048).

Conclusion: Our results support the involvement of inflammatory pathways in structural brain changes in BD.
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http://dx.doi.org/10.1017/S1092852921000596DOI Listing
June 2021

The Relationship Between Plasma Oxytocin and Executive Functioning in Huntington's Disease: A Pilot Study.

J Huntingtons Dis 2021 Jun 4. Epub 2021 Jun 4.

Department of Neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX, USA.

The role of oxytocin (OT) in social cognition of patients with Huntington's disease (HD) has been studied, but its impact on executive functioning has not been explored yet. Healthy controls, premanifest HD, and manifest HD participants underwent executive functioning assessment and OT plasma measurement. There were no significant group differences in plasma OT levels. Higher OT levels were associated with better executive functioning in premanifest HD participants. Our findings revealed an association between OT levels and depressive symptoms in premanifest and manifest HD participants. The potential role of OT in HD deserves further investigation.
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http://dx.doi.org/10.3233/JHD-210467DOI Listing
June 2021

Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells.

Neuroimmunomodulation 2021 5;28(3):99-107. Epub 2021 May 5.

Institute of Education and Research, Santa Casa BH, Belo Horizonte, Brazil.

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. However, the mechanisms underlying this enhanced inflammation are not well understood. There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context. Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells). Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as: (i) failure to develop adequate stress-related responses, (ii) indirectly through microglial activation, (iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and (iv) dysbiosis. In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders. A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies.
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http://dx.doi.org/10.1159/000515594DOI Listing
May 2021

Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer's disease.

Transl Psychiatry 2021 04 28;11(1):251. Epub 2021 Apr 28.

Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Alzheimer's disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.
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http://dx.doi.org/10.1038/s41398-021-01349-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080782PMC
April 2021

The Relationship Between Plasma BDNF and Pain in Older Adults With Knee Osteoarthritis.

Biol Res Nurs 2021 Apr 29:10998004211012479. Epub 2021 Apr 29.

Department of Research, Cizik School of Nursing, 12340The University of Texas Health Science Center at Houston, TX, USA.

Osteoarthritis (OA) is the most prevalent cause of chronic pain and disability in people aged ≥45 years, with the knee being the most affected joint. Neurotrophic factors like brain-derived neurotrophic factor (BDNF), which promotes neurogenesis and neuroplasticity, have been shown to significantly affect chronic pain. This study aimed to investigate the relationship between resting plasma BDNF levels and clinical pain and quantitative sensory testing measures in older adults with knee OA pain. For this secondary analysis, a previously reported dataset was used comprised of older adults with knee OA who underwent quantitative sensory testing. A comprehensive generalized linear model (GLM) was built to understand the relationships between BDNF and important covariates, followed by the elastic net (EN) method for variable selection. GLM was then performed to regress BDNF levels against only the variables selected by EN. The mean age of the sample was 60.4 years ( = 9.1). Approximately half of the participants were female (53%). Plasma BDNF levels were positively associated with heat pain threshold and the numeric rating scale of pain. Future mechanistic studies are needed to replicate and extend these findings to advance our knowledge of the underlying mechanisms of BDNF in knee OA and other chronic pain conditions.
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http://dx.doi.org/10.1177/10998004211012479DOI Listing
April 2021

Induced Pluripotent Stem Cells (iPSCs) Technology: Potential Targets for Depression.

Adv Exp Med Biol 2021 ;1305:493-501

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Major depressive disorder (MDD) is a heterogeneous condition with complex pathophysiology resulting from the interaction between genetic and environmental factors. Despite a reasonable array of therapeutic options, the management of MDD has been marked by an increasing number of treatment resistant cases. Identifying the multiple pathways involved in the pathogenesis of MDD is fundamental to move the field forward and to define novel and more effective therapeutic targets. The current disease models are not able to recapitulate the complexity of this condition. In the last years, induced pluripotent stem cells (iPSCs) have emerged as a unique tool to help the elucidation of the pathophysiology of psychiatric disorders through disease modeling. In addition, the iPSCs may play an important role in the validation of new therapeutic targets.
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http://dx.doi.org/10.1007/978-981-33-6044-0_24DOI Listing
April 2021

Microglia Activation in Basal Ganglia Is a Late Event in Huntington Disease Pathophysiology.

Neurol Neuroimmunol Neuroinflamm 2021 05 1;8(3). Epub 2021 Apr 1.

From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders (N.P.R.), Department of Neurology, McGovern Medical School, The University of Texas Health Science Center, Houston; Department of Neurology (O.C., L.F.), The University of Texas at Austin; School of Medicine (L.B.L.), University of Washington, Seattle; Neuropsychiatry Program (G.D.C., A.L.T.), Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston; Houston Methodist Research Institute and Weill Cornell Medicine (P.Z.-F., M.Y.), TX; and HDSA Center of Excellence at University of Texas Health Science Center at Houston (E.F.S.).

Objective: To define the role played by microglia in different stages of Huntington disease (HD), we used the TSPO radioligand [11C]-ER176 and PET to evaluate microglial activation in relation to neurodegeneration and in relation to the clinical features seen at premanifest and manifest stages of the disease.

Methods: This is a cross-sectional study in which 18 subjects (6 controls, 6 premanifest, and 6 manifest HD gene carriers) underwent a [11C]-ER176 PET scan and an MRI for anatomic localization. Segmentation of regions of interest (ROIs) was performed, and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR). Microglial activation was correlated with ROIs volumes, disease burden, and the scores obtained in the clinical scales. As an exploratory aim, we evaluated the dynamic functions of microglia in vitro, by using induced microglia-like (iMG) cells from peripheral blood monocytes.

Results: Individuals with manifest HD present higher [11C]-ER176 SUVR in both globi pallidi and putamina in comparison with controls. No differences were observed when we compared premanifest HD with controls or with manifest HD. We also found a significant correlation between increased microglial activation and cumulative disease burden, and with reduced volumes. iMG from controls, premanifest HD, and manifest HD patients showed similar phagocytic capacity.

Conclusions: Altogether, our data demonstrate that microglial activation is involved in HD pathophysiology and is associated with disease progression.
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http://dx.doi.org/10.1212/NXI.0000000000000984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017723PMC
May 2021

Decreased Plasma Levels of Angiotensin-Converting Enzyme Among Patients With Bipolar Disorder.

Front Neurosci 2021 11;15:617888. Epub 2021 Feb 11.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

Background: Dysfunctions in the renin-angiotensin system (RAS) seem to be involved in the pathophysiology of several mental illness, including schizophrenia and mood disorders. We carried out a cross-sectional study assessing the levels of RAS-related molecules among bipolar disorder (BD) patients compared to healthy controls.

Methods: our sample consisted of 30 outpatients with BD type 1 (10 males, 20 females, age = 35.53 ± 10.59 years, 14 euthymic, 16 experiencing mood episodes) and 30 healthy controls (10 males, 20 females, age = 34.83 ± 11.49 years). Plasma levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin-II (Ang II), and angiotensin (1-7) [Ang-(1-7)] were determined by ELISA.

Results: BD patients experiencing ongoing mood episodes had significantly lower ACE levels compared to controls (median: 459.00 vs. 514.10, < 0.05). There was no association between the levels of these biomarkers and clinical parameters.

Conclusion: Our findings support the involvement of RAS dysfunction in the pathophysiology of BD. Considering the potential therapeutic implications linked to a better understanding of the role of RAS dysfunction in BD, studies allowing a better characterization of RAS-related molecules level and activity across different mood states are of high interest.
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http://dx.doi.org/10.3389/fnins.2021.617888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904895PMC
February 2021

Nutrition-based interventions for mood disorders.

Expert Rev Neurother 2021 Mar 3;21(3):303-315. Epub 2021 Mar 3.

Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, Texas, United States.

: 'Nutritional Psychiatry' is an emerging area of research that has great potential as an adjunctive tool for the prevention and treatment of diverse neuropsychiatric disorders. Several nutrition-related aspects, such as obesity, dietary patterns, gut microbiome composition and gut permeability, bioactive food compounds, and nutrients can influence pathways implicated in the pathophysiology of mood disorders.: Here, the authors review the current evidence on nutrition-mood interaction and nutrition-based treatments for the two main mood disorders, i.e., major depressive disorder and bipolar disorder.: Consistent evidence from observational studies has pointed out the association between a 'healthy' diet, generally characterized by a higher intake of fruits, vegetables, legumes, nuts, whole grains, and good quality sources of protein (i.e. fish and/or seafood), and decreased risk of mood disorders and the parallel association between a 'Western' diet pattern and increased risk. However, only a few clinical trials have evaluated the effect of nutritional interventions on the treatment of these conditions. The bidirectional interaction between the brain and the gut, named 'brain-gut-microbiome axis' or 'gut-brain axis', plays a key role in the link between nutrition and mood disorders. Therefore, nutrition-based strategies for gut microbiota modulation are promising fields in mood disorders.
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http://dx.doi.org/10.1080/14737175.2021.1881482DOI Listing
March 2021

Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection.

Microb Pathog 2021 Feb 21;151:104745. Epub 2021 Jan 21.

Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-γ, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-γ and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.
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http://dx.doi.org/10.1016/j.micpath.2021.104745DOI Listing
February 2021

Peripheral Levels of Renin-Angiotensin System Components Are Associated With Cognitive Performance in Huntington's Disease.

Front Neurosci 2020 18;14:594945. Epub 2020 Dec 18.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.

The renin-angiotensin system (RAS) has proven to be involved in the pathophysiology of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD), serving as a potential therapeutic target and a disease burden marker. Studies have associated negative clinical outcomes with the activation of the classical RAS arm composed of the angiotensin-converting enzyme (ACE) and angiotensin (Ang) II, while suggested positive outcomes with the activation of the counter-regulatory RAS arm involving ACE2 and Ang-(1-7). Huntington's disease (HD) shares many pathological and clinical outcomes with AD and PD, but the evidence of direct involvement of RAS components in the pathophysiology of HD is still limited and needs further investigation. Herein, we investigated peripheral levels of the RAS components Ang II, Ang-(1-7), ACE, and ACE2 in controls, premanifest, and manifest HD gene carriers and their relationship with clinical outcomes. Peripheral blood samples were collected via phlebotomy, and plasma concentrations of RAS components were measured by Enzyme-Linked Immunosorbent Assay. Clinical evaluation included a questionnaire about socio-demographic characteristics, motor, and cognitive assessments. Results showed (1) no significant group differences in plasma concentrations of RAS components; (2) positive correlations between ACE2 and Verbal Fluency Test (VFT) scores; and (3) negative correlations between Ang II and Mini-Mental State Examination scores. These results corroborate the proposed balance between the classical (ACE/Ang II) and the counter-regulatory [ACE2/Ang-(1-7)] arms of the RAS, with the former associated with negative clinical outcomes and the latter with positive effects in HD.
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http://dx.doi.org/10.3389/fnins.2020.594945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775387PMC
December 2020

Interleukin-6 response to insulin-induced hypoglycemia is associated with hypothalamic-pituitary-adrenal axis activation.

J Neuroimmunol 2020 Nov 13;350:577446. Epub 2020 Nov 13.

Servico de Endocrinologia do Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Increased plasma levels of interleukin-6 (IL-6) in response to acute hypoglycemia have been well documented. Aiming to study the interaction between IL-6 and counter-regulatory hormones during hypoglycemic stress we conducted an exploratory single center study involving 26 adult patients undergoing insulin tolerance test. Insulin-induced hypoglycemia elicited a significant dynamic response of IL-6, adrenaline, noradrenaline, GH, prolactin, ACTH and serum and salivary cortisol (P < 0.001 for all variables). Patients with insufficient HPA axis response had lower hypoglycemia-induced IL-6 increase (median: 0.88 pg/mL) compared with individuals with intact HPA axis response (2.03 pg/mL, P = 0.007). IL-6 maximal increase correlated with the maximal increase of serum cortisol (r = 0.48; P = 0.013), salivary cortisol (r = 0.66; P = 0.012), plasma ACTH (r = 0.48; P = 0.013) and with the increase in procedure-related symptoms of anxiety and hypoglycemia (r = 0.57; P = 0.003). In conclusion, hypoglycemic stress-induced IL-6 increase is associated with activation of the HPA axis, suggesting that IL-6 response to hypoglycemic stress may be regarded as part of the counter-regulatory response, possibly contributing to the maintenance of glucose homeostasis.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577446DOI Listing
November 2020

Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease.

J Neurovirol 2021 02 3;27(1):70-79. Epub 2020 Nov 3.

Neuropsychiatry Program, Department of Psychiatry & Behavioral Science, University of Texas Health Sciences Center At Houston, Houston, TX, 77204, USA.

Symptoms of depression are common among persons with HIV (PWH) and can have a significant impact on socioeconomic and personal well-being, but little is known about their neurobiological substrates in the context of HIV disease. This study examined the possible role of brain-derived neurotrophic factor (BDNF) in symptoms of depression and other aspects of mood in 109 PWH and 43 seronegative participants aged 50 and older. Participants completed the Profile of Mood States (POMS) which measured six dimensions of mood and was normatively adjusted for sex. A model controlling for medical comorbidities and substance use diagnoses among PWH showed a significant interaction between BDNF and POMS subscales. Planned post hoc analyses revealed that lower BDNF was only associated with higher scores on Depression-Dejection and Confusion-Bewilderment POMS subscales among PWH and at small-to-medium effect sizes. Lower levels of BDNF were associated with AIDS diagnoses and CD4 count, but not with viremia or duration of infection. BDNF levels did not differ between the PWH and HIV - samples, and there were no significant correlations between BDNF and any POMS variable in the HIV - group. Findings implicate BDNF in the neuropathophysiology of specific depressive symptoms in the context of HIV disease. Future studies may examine whether BDNF levels change over time, are sensitive to other aspects of mood disorders in HIV, and are associated with markers of HIV-associated neural injury.
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http://dx.doi.org/10.1007/s13365-020-00916-2DOI Listing
February 2021

Corrigendum to "Leishmania infantum pyridoxal kinase evaluated in a recombinant protein and DNA vaccine to protects against visceral leishmaniasis". Molecular Immunology 124 (2020) 161-171.

Mol Immunol 2020 Dec 15;128:55. Epub 2020 Oct 15.

Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.molimm.2020.09.002DOI Listing
December 2020

Prevalence and risk factors for post-traumatic stress, anxiety, and depression in sepsis survivors after ICU discharge.

Braz J Psychiatry 2021 May-Jun;43(3):269-276

Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical (PPG-IMT), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Objective: Sepsis survivors present a wide range of sequelae; few studies have evaluated psychiatric disorders after sepsis. The objective of this study was to define the prevalence of and risk factors for anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in sepsis survivors.

Method: Anxiety, depression and post-traumatic stress symptoms in severe sepsis and septic shock survivors 24 h and 1 year after intensive care unit (ICU) discharge were assessed using the Beck Anxiety/Depression Inventories and the PTSD Checklist-Civilian Version. Differences in psychiatric symptoms over time and the influence of variables on these symptoms were calculated with marginal models.

Results: A total of 33 patients were enrolled in the study. The frequencies of anxiety, depression and PTSD 24 h after ICU discharge were 67%, 49%, and 46%, respectively and, among patients re-evaluated 1 year after ICU discharge, the frequencies were 38%, 50%, and 31%, respectively. Factors associated with PTSD included serum S100B level, age, and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score. Factors associated with depression included patient age and cumulative dose of dobutamine. IQCODE score and cumulative dose of haloperidol in the ICU were associated with anxiety after ICU discharge.

Conclusion: Patients who survive sepsis have high levels of psychiatric symptoms. Sepsis and associated treatment-related exposures may have a role in increasing the risk of subsequent depression, anxiety, and PTSD.
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http://dx.doi.org/10.1590/1516-4446-2020-0986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136386PMC
June 2021

Oxidative DNA damage is increased in older adults with a major depressive episode: A preliminary study.

J Affect Disord 2021 01 24;279:106-110. Epub 2020 Sep 24.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: DNA oxidative damage is a marker of increased oxidative stress activity. Elevated DNA oxidative damage has been associated with major depressive disorder in young adults, but there is no information about DNA oxidative damage in late-life depression. This study aims to evaluate whether older adults with late-life depression (LLD) has increased DNA oxidative damage compared to healthy older adults.

Methods: We included 92 participants (57 with LLD [73.2 ± 7.7 years-old] and 35 non-depressed subjects (Controls) [70.5 ± 7.4 years-old]). We analyzed the plasma 8‑hydroxy-2'-deoxyguanosine (8-oxo-dG), a marker of DNA oxidation, using a commercially-available ELISA assay.

Results: LLD participants had significantly higher 8-oxo-DG levels compared to controls (P<0.001). 8-oxo-dG levels were significantly correlated with depressive symptoms as assessed by the Hamilton Depression Rating Scale (rho=0.34, p<0.001). The plasma levels of 8-OHdG were not significantly correlated with other clinical, neurocognitive, and demographic variables.

Limitations: Our current results are limited by the relatively small sample size, cross-sectional design, and the recruitment of participants in tertiary center for assessment and treatment of LLD.

Conclusions: Older adults with LLD have increased DNA oxidative damage. Our findings provide additional evidence for elevated oxidative stress activity in LLD and the possible activation of age-related biological pathways and enhanced biological aging changes in LLD.
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http://dx.doi.org/10.1016/j.jad.2020.09.084DOI Listing
January 2021

Social vulnerability: The connection between psychiatric disorders and thiamine deficiency in pregnant women.

Psychiatry Res 2020 11 20;293:113362. Epub 2020 Aug 20.

Graduate program in Neurosciences, Laboratorio of Molecular and Behavioural Neuroscience, Federal University of Minas Gerais, Belo Horizonte, Brazil.

The evaluation of thiamine and its derivative phosphate esters levels in pregnant women in rural communities can contribute not only for understanding the specific characteristics of this population regarding nutritional aspects, but also for clarifying the relations of psychiatric manifestations and a vitamin deficit. In the present work we assessed sociodemographic variables, psychiatric parameters and thiamine and its derivative in the whole blood of women in a rural, low-income community in Brazil. A case-control study was done. 94 women were divided in groups using the trimesters of pregnancy as a criterion: each trimester, 1st, 2nd and 3rd had 17, 37 and 38 women, respectively. A control group of non-pregnant women (n-39) was also included. Symptoms of anxiety and depression were assessed using the HAMA Scale and Beck Inventory, respectively. The thiamine and its phosphorylated derivatives concentrations were determined in whole blood samples using the HPLC method. The results suggest that physiological mechanisms linked to the metabolic pathways of thiamine may play a role in some neurobiological substrate involved in the regulation of emotional state. Thus, social vulnerability is identified as an important factor to be considered in the evaluation of the mental health of pregnant women living in rural communities.
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http://dx.doi.org/10.1016/j.psychres.2020.113362DOI Listing
November 2020

Effect of immune activation on the kynurenine pathway and depression symptoms - A systematic review and meta-analysis.

Neurosci Biobehav Rev 2020 11 24;118:514-523. Epub 2020 Aug 24.

Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), 1941 East Rd, Houston, TX, 77054, USA; Houston Methodist Research Institute, Institute for Academic Medicine, 6670 Bertner St., Houston, TX, 77030, USA. Electronic address:

Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN/TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N = 315 medically ill patients treated with interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (IFN-α, interferon-beta IFN-β, and lipopolysaccharide LPS). We found that IFN-α treatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses is likely mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression.
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http://dx.doi.org/10.1016/j.neubiorev.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087452PMC
November 2020

Copeptin response to hypoglycemic stress is linked to prolactin activation in children.

Pituitary 2020 Dec;23(6):681-690

Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, Brazil.

Purpose: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents.

Methods: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia.

Results: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (r = 0.30; P = 0.010), cortisol (r = 0.33; P = 0.003), prolactin (r = 0.25; P = 0.03), IL-6 (r = 0.35; P = 0.008) and with BMI-SDS (r = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004).

Conclusion: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.
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http://dx.doi.org/10.1007/s11102-020-01076-6DOI Listing
December 2020

A Leishmania amastigote-specific hypothetical protein evaluated as recombinant protein plus Th1 adjuvant or DNA plasmid-based vaccine to protect against visceral leishmaniasis.

Cell Immunol 2020 10 13;356:104194. Epub 2020 Aug 13.

Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Most studies evaluating vaccine candidates against visceral leishmaniasis (VL) have used parasite promastigote-expressed antigens; however, Leishmania proteins expressed in the amastigote forms should be considered, since few hours after infection this stage comes into contact with the host immune system and is responsible for the development of the disease. In this context, in the present study, a Leishmania amastigote-specific hypothetical protein, called LiHyJ, was evaluated as a recombinant protein plus saponin as an adjuvant or DNA vaccine to protect against VL. The vaccine effect was evaluated by means of the evaluation of immunological and parasitological analyses performed in BALB/c mice against Leishmania infantum infection. Results showed that rLiHyJ/saponin and DNA LiHyJ induced significantly higher levels of anti-protein and anti-parasite IFN-γ, IL-12, GM-CSF, and IgG2a isotype antibodies, which were associated with a low presence of IL-4 and IL-10. DNA vaccination induced higher IFN-γ production, mainly by CD8 T cells, while rLiHyJ/saponin stimulated the production of this cytokine, mainly by CD4 T cells. The parasite load evaluated in distinct organs showed that both immunization schedules significantly reduced organic parasitism, when compared to the controls. Similar results were found in the immunological and parasitological assays when using the recombinant protein or DNA, although the vaccination with rLiHyJ plus saponin induced a slightly higher Th1 response and lower parasite load, when compared to the use of DNA plasmid. The protein also proved to be immunogenic when peripheral blood mononuclear cells of treated VL patients and healthy subjects were in vitro stimulated, since higher IFN-γ and lower IL-4 and IL-10 levels were found in the culture supernatants. In conclusion, LiHyJ should be considered in future studies as a vaccine candidate to protect against VL.
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http://dx.doi.org/10.1016/j.cellimm.2020.104194DOI Listing
October 2020

A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against infection.

NPJ Vaccines 2020 13;5:75. Epub 2020 Aug 13.

Neisseria Research Group, Molecular Microbiology, School of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, SO16 6YD UK.

Leishmaniases are neglected diseases caused by infection with parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4 and CD8 T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.
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http://dx.doi.org/10.1038/s41541-020-00224-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426426PMC
August 2020

Early Post-stroke Depressive Symptoms are Associated with Low Peripheral Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and Glial Cell-derived Neurotrophic Factor (GDNF).

Curr Neurovasc Res 2020 ;17(4):495-501

Instituto de Ensino e Pesquisa, Santa Casa BH, Belo Horizonte, Brazil.

Background: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management.

Objective: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms.

Methods: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers.

Results: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels.

Conclusion: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke.
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http://dx.doi.org/10.2174/1567202617999200819155636DOI Listing
January 2020
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