-
The Journal of Comparative Neurology Feb 2023The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital...
The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we describe the efferent projections from the five divisions of the ORB to the thalamus in the rat. We demonstrated that, with some overlap, each division of the ORB distributed in a distinct (and unique) manner to nuclei of the thalamus. Overall, ORB projected to a relatively restricted number of sites in the thalamus, and strikingly distributed entirely to structures of the medial/midline thalamus, while completely avoiding lateral regions or principal nuclei of the thalamus. The main termination sites in the thalamus were the paratenial nucleus (PT) and nucleus reuniens (RE) of the midline thalamus, the medial (MDm) and central (MDc) divisions of the mediodorsal nucleus, the intermediodorsal nucleus, the central lateral, paracentral, and central medial nuclei of the rostral intralaminar complex and the submedial nucleus (SM). With some exceptions, medial divisions of the ORB (MO, VO) mainly targeted "limbic-associated" nuclei such as PT, RE, and MDm, whereas lateral division (VLO, LO, DLO) primarily distributed to "sensorimotor-associated" nuclei including MDc, SM, and the rostral intralaminar complex. As discussed herein, the medial/midline thalamus may represent an important link (or bridge) between the orbital cortex and the hippocampus and between the ORB and medial prefrontal cortex. In summary, the present results demonstrate that each division of the orbital cortex projects in a distinct manner to nuclei of the thalamus which suggests unique functions for each division of the orbital cortex.
Topics: Animals; Rats; Prefrontal Cortex; Thalamus; Midline Thalamic Nuclei; Hippocampus; Intralaminar Thalamic Nuclei; Phytohemagglutinins; Neural Pathways
PubMed: 36226328
DOI: 10.1002/cne.25419 -
Frontiers in Immunology 2021The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a...
BACKGROUND
The differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.
METHODS
Patients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.
RESULTS
A total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity.
CONCLUSIONS
The diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.
Topics: Adult; Antigens, Bacterial; Biomarkers; Cerebrospinal Fluid; China; Cohort Studies; Diagnosis, Differential; Enzyme-Linked Immunospot Assay; Female; Humans; Interferon-gamma; Male; Meningitis, Bacterial; Middle Aged; Models, Biological; Mycobacterium tuberculosis; Tuberculosis, Meningeal
PubMed: 34867952
DOI: 10.3389/fimmu.2021.731876 -
Clinical and Experimental Immunology Oct 2019Hepatic stellate cells (HSCs) have a central role in liver inflammation and fibrosis by producing inflammatory and fibrotic mediators. Their activation is regulated...
Hepatic stellate cells (HSCs) have a central role in liver inflammation and fibrosis by producing inflammatory and fibrotic mediators. Their activation is regulated through direct cell-cell interactions, but also through systemic and local effects of soluble factors such as cytokines. The effects of the proinflammatory cytokines interleukin (IL)-17 and tumor necrosis factor (TNF)-α and cell interactions with hepatocytes on HSC activation were assessed. Human HSC and HepaRG cells were exposed to IL-17 and/or TNF-α. IL-17 and TNF-α contribution from immune cells was determined in a co-culture model with phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC), HSC and/or hepatocytes. IL-17 enhanced TNF-α effects on the induction of IL-6, IL-1β, and the chemokine IL-8, chemokine (C-C motif) ligand 20 (CCL20) and monocyte chemoattractant protein-1 (MCP-1) expression/secretion in isolated HSC cultures. HSC-hepatocyte interactions did not enhance IL-6, IL-8 and CCL20 production compared to hepatocyte alone. However, HSC-hepatocyte interactions increased C-reactive protein expression. IL-17 and/or TNF-α had no direct profibrotic effects on collagen 1 α1, tissue inhibitor of matrix metalloproteinase (TIMP) and matrix metalloproteinase (MMP) 2 gene expression, whereas mRNA levels of MMP3, an enzyme involved in matrix destruction, were up-regulated in HSCs. The use of specific inhibitors of IL-17 and TNF-α indicated their contribution to the strong increase of IL-6 and IL-8 production induced by PBMC, HSC and/or hepatocyte interactions. As chronic liver inflammation leads to liver fibrosis, IL-17 and/or TNF-α neutralization can be of interest to control liver inflammation and therefore its effects on fibrosis.
Topics: Cells, Cultured; Chemokine CCL2; Chemokine CCL20; Collagen Type I; Cytokines; Hepatic Stellate Cells; Hepatocytes; Humans; Inflammation; Interleukin-17; Leukocytes, Mononuclear; Liver; Liver Cirrhosis; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha
PubMed: 31102558
DOI: 10.1111/cei.13316 -
Scientific Reports Aug 2022Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly...
Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly understood. In a population-based birth cohort, we measured peripheral blood mononuclear cell responses (28 cytokines) to respiratory viruses and bacteria, Toll-like receptor ligands and phytohemagglutinin, in 307 children. Cytokine responses were highly variable with > 1000-fold differences between children. Machine learning revealed clear distinction between virus-associated and bacteria-associated stimuli. Cytokines clustered into three functional groups (anti-viral, pro-inflammatory and T-cell derived). To investigate mechanisms potentially explaining such variable responses, we investigated cytokine Quantitative Trait Loci (cQTLs) of IL-6 responses to bacteria and identified nine (eight novel) loci. Our integrative approach describing stimuli, cytokines and children as variables revealed robust immunologically and microbiologically plausible clustering, providing a framework for a greater understanding of host-responses to infection, including novel genetic associations with respiratory disease.
Topics: Bacteria; Child; Cytokines; Humans; Leukocytes, Mononuclear; Toll-Like Receptors; Viruses
PubMed: 35931775
DOI: 10.1038/s41598-022-16509-4 -
Iranian Journal of Microbiology Oct 2022Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Peripheral blood monocytes cells (PBMCs) may have altered function to some...
BACKGROUND AND OBJECTIVES
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Peripheral blood monocytes cells (PBMCs) may have altered function to some extent in women with endometriosis. is a probiotic bacterium within the human body with the ability of alleviating many inflammatory diseases. Here, we examined the effect of on PBMCs of endometriosis patients.
MATERIALS AND METHODS
In this study, peripheral blood samples were obtained from endometriosis patients (n=11) and non-endometriosis individuals (n=11). After isolation of peripheral blood mononuclear cells with Ficoll, cells were cultured in the presence and absence of phytohemagglutinin. Also, these cells were co-cultured with 1×10 CFU/ml of IL-6 and IL-1 cytokines were measured by ELISA method and the two groups were evaluated and compared.
RESULTS
The results showed that in endometriosis patients, the production of pro-inflammatory cytokines, including IL-1 and IL-6, by PBMC was increased compared to non-endometriosis subjects, and stimuli such as PHA intensified this elevation. Also, increased the levels of pro-inflammatory cytokines including IL-1 and IL-6. However, the production of these cytokines decreased due to the modulatory properties of bacterial cells after 48 h.
CONCLUSION
According to the results of the current study, IL-1 and IL-6 production was significantly increased in PMBCs of endometriosis patients compared to that of the healthy controls. Also, was considered as an antigenic compound and induced IL-1 and IL-6 production. According to these results, probiotics can be further used for the treatment of endometriosis patients and more investigations are needed to confirm these results.
PubMed: 36531824
DOI: 10.18502/ijm.v14i5.10965 -
Vaccines Jun 2021HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing mice with HLA-E monomeric, α-heavy chain (αHC)... (Review)
Review
HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing mice with HLA-E monomeric, α-heavy chain (αHC) open conformers (OCs). Two mAbs (TFL-006 and TFL-007) were bound to the αHC's coated on a solid matrix. The binding was inhibited by the peptide AYDGKDY, present in all alleles of the six HLA-I isoforms but masked by β2-microglobulin (β2-m) in intact HLA-I trimers (closed conformers, CCs). IVIg preparations administered to lower anti-HLA Abs in pre-and post-transplant patients have also shown HLA-I polyreactivity. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might also possess the immunomodulatory capabilities of IVIg. We tested the relative binding affinities of the mAbs and IVIg for both OCs and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells; (b) the production of anti-HLA-II antibody (Ab) by B-memory cells and anti-HLA-I Ab by immortalized B-cells; and (c) the upregulation of CD4+, CD25+, and Fox P+ T-regs. The mAbs bound only to OC, whereas IVIg bound to both CC and OC. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells and anti-HLA Ab production by B-cells and expanded T-regs better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal, therapeutic IVIg-mimetic.
PubMed: 34205517
DOI: 10.3390/vaccines9060680 -
BMC Psychiatry Mar 2023Based on its objective characteristics, laboratory markers have always been the research direction of clinical diagnosis and assessment of mental disorders including...
BACKGROUND
Based on its objective characteristics, laboratory markers have always been the research direction of clinical diagnosis and assessment of mental disorders including Alzheimer's disease.
METHODS
MTT Colorimetric Assay, ELISA, and quantitative PCR were used to investigate the responsiveness of peripheral blood mononuclear cells (PBMCs) to mitogen Lipopolysaccharides (LPS) and Phytohemagglutinin (PHA), PBMCs genomic methylation and hydroxymethylation levels, nuclear DNA and mitochondrial DNA damage, respiratory chain enzyme activities, and circulating cell-free mitochondrial DNA levels were detected in 90 patients with Alzheimer's disease.
RESULTS
In the Alzheimer's disease group, LPS stimulated PBMCs viability, TNF-α secretion, PHA stimulated IL-10 secretion, genomic DNA methylation levels, circulating cell-free mitochondrial DNA copies, citrate synthase activity were reduced compared to the control; while the LPS stimulated PBMCs IL-1α secretion, PHA stimulated IL-1α and IFN-γ secretion, plasma IL-6 and TNF-α, mitochondrial DNA damages were increased compared to the control.
CONCLUSIONS
The reactivity of peripheral blood mononuclear cells to mitogens, mitochondrial DNA integrity characteristics, and cell-free mitochondrial DNA copies may be used as candidate laboratory biomarkers to help clinical management of Alzheimer's disease.
Topics: Humans; Mitogens; Lipopolysaccharides; Leukocytes, Mononuclear; Tumor Necrosis Factor-alpha; Cytokines; DNA, Mitochondrial; Alzheimer Disease; Phytohemagglutinins
PubMed: 36890488
DOI: 10.1186/s12888-023-04634-x -
Frontiers in Immunology 2022Extracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model....
INTRODUCTION
Extracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model. However, the effects of acellular amniotic fluid (acAF) or AF-EVs on the T-Cell immune response have not been explored.
METHODS
In this study, we investigated the effects of acAF and AF-EVs on the T cell immune response in an in vitro cell culture model. Peripheral Blood Mononuclear Cells (PBMCs) were stimulated with Phytohemagglutinin (PHA) to induce the immune response and were subsequently treated with either serum-free media (vehicle), acAF, or concentrated AF-EVs.
RESULTS
Both acAF and AF-EV treatment suppressed PHA-induced T cell proliferation and PHA-induced T cell activation; however, treatment with concentrated AF-EVs had a greater effect. Additionally, both acAF and AF-EVs reduced PBMC pro-inflammatory cytokine release. AF-EVs were found to be taken up by both CD4+ and CD8+ effector T cell subsets.
CONCLUSION
Overall, this data demonstrates that AF-EVs have a robust immunomodulatory effect on T cells and suggests AF-EVs could be used as an immunotherapeutic tool.
Topics: Animals; Mice; Humans; Amniotic Fluid; Leukocytes, Mononuclear; Extracellular Vesicles; Cytokines; Immunity
PubMed: 36518766
DOI: 10.3389/fimmu.2022.977809 -
Iranian Journal of Basic Medical... Apr 2020Nowadays, ionizing radiation (IR) has a significant contribution to the diagnostic and therapeutic medicine, and following that, health risks to individuals through...
OBJECTIVES
Nowadays, ionizing radiation (IR) has a significant contribution to the diagnostic and therapeutic medicine, and following that, health risks to individuals through unexpected exposure is greatly increased. Therefore, biological and molecular technology for estimation of dose (biodosimetry) is taken into consideration. In biodosimetry methods stimulation of cells to proliferation is routine to achieve more sensitivity of techniques. However, this concept has recently been challenged by new molecular methods such as gene expression analysis. This study aims to investigate the stimulation effects on gene expression biodosimetry.
MATERIALS AND METHODS
The blood samples were taken from15 patients who were irradiated by TC-99 MIBI, before radiopharmaceutical injection and 24 hr after injection. Lymphocytes were extracted immediately and activated by (phytohemagglutinin) PHA for 24 hr and XPA and FDXR expression levels were investigated by employing relative quantitative Real-Time PCR.
RESULTS
The results of this study show a significant increase in the FDXR expression level and a significant decrease in the XPA after stimulation of irradiated lymphocytes. Interestingly, a significant increasing trend in the FDXR expression level (at 0.05 significance level) following cell stimulation to the division was observed.
CONCLUSION
Our results suggest that the PHA activation role in gene expression-based biodosimetry is strongly depended on the target genes and the relevant protein pathways. Finally, cell stimulation looks to be useful for some specific genes, such as FDXR, due to the increasing trend in expression and improvement of sensitivity of gene expression-based biodosimetry method.
PubMed: 32489559
DOI: 10.22038/ijbms.2020.42350.9997 -
Veterinary World Jun 2022The reports from the Ministry of Agriculture and Fisheries suggest that camels suffer less compared to goats, sheep, and cows from a number of common infectious diseases...
BACKGROUND AND AIM
The reports from the Ministry of Agriculture and Fisheries suggest that camels suffer less compared to goats, sheep, and cows from a number of common infectious diseases in Oman. However, there is no immunological evidence to substantiate this claim. This present study is, therefore, an attempt to study the immunological responses of camels, goats, sheep, and cows by comparing their oxidative respiratory burst of peripheral blood leukocytes (PBLs) as a marker of innate immunity occurring during phagocytosis and the mitogenic responses of their peripheral blood mononuclear leukocytes (PBMLs) as a marker of their adaptive immune response.
MATERIALS AND METHODS
Ten female adult animals (n = 10) were selected from each species (goats, sheep, and cows). The goats, sheep, and cows were maintained at the Agricultural Experiment Station, while camels were kept at the Royal Camel Corps (RCC). Blood samples were collected from the jugular vein in 7 mL of heparin and ethylenediaminetetraacetic acid vacutainer tubes. The oxidative respiratory burst of PBLs was measured using a chemiluminescence (CL) assay. Reactants consisted of 75 mL of whole blood diluted (1:50), 75 mL of luminol/isoluminol, and 75 mL of zymosan opsonized with non-heat inactivated serum/heat-inactivated serum or non-opsonized zymosan. CL responses were measured as relative light units and expressed as the mean count per minute and peak CL values. The mitogenic response of PBMLs to concanavalin A (Con-A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) was tested using a WST-8 assay and read spectrophotometrically at 450 nm.
RESULTS
The present findings showed that camel PBLs generate significantly higher CL responses, both intracellularly as well as extracellularly, with zymosan opsonized with autologous serum. Camel PBLs demonstrated a significantly higher (p = 0.001) response when stimulated with zymosan opsonized with heat-inactivated serum compared to those of goat, sheep, and cow lymphocytes from camels exhibited significantly higher (p = 0.001) stimulation indices (SI) with Con-A, PHA, and PWM.
CONCLUSION
The present study suggests that camels are capable of mounting both superior innate as well as adaptive immune responses and provide immunological evidence supporting the belief of some authors, who have proposed that camels are less susceptible to a number of common infectious diseases than other domesticated ruminants.
PubMed: 35993061
DOI: 10.14202/vetworld.2022.1398-1407