In vivo vitamin C supplementation increases phosphoinositol transfer protein expression in peripheral blood mononuclear cells from healthy individuals

The objective of this study was to examine the effect of daily probiotic supplementation upon the immune profile of healthy participants by the assessment of ex vivo cytokine production. Twenty healthy adult volunteers received a multi-strain probiotic supplement consisting of two strains of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured ex vivo in the presence or absence of lipopolysaccharide and cytokine production was assessed. Postintervention, a significant decrease in the production of interleukin-6 and interleukin-1β was apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst a significant increase in IL-10 and transforning growth factor-β production was seen when the cells were incubated without an additional stimulus. This preliminary study demonstrates the potential of a multi-strain probiotic supplement to alter the immune response as demonstrated by changes in ex vivo cytokine production. Such results demonstrate the potential benefit of probiotic supplementation for healthy individuals and warrants further investigation.

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In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.4.1233-1240.2003 ◽

2003 ◽

Vol 47 (4) ◽

pp. 1233-1240 ◽

Cited By ~ 23

Author(s):

Fatih M. Uckun ◽

Chun-Lin Chen ◽

Peter Samuel ◽

Sharon Pendergrass ◽

T. K. Venkatachalam ◽

...

Keyword(s):

Dose Level ◽

Peripheral Blood Mononuclear Cells ◽

Feline Immunodeficiency Virus ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Immunodeficiency Virus ◽

Blood Mononuclear Cells ◽

Antiretroviral Activity

ABSTRACT Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient ≥1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a ≥1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound.

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Systemic and Extraradicular Bacterial Translocation in Apical Periodontitis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.649925 ◽

2021 ◽

Vol 11 ◽

Author(s):

María José Bordagaray ◽

Alejandra Fernández ◽

Mauricio Garrido ◽

Jessica Astorga ◽

Anilei Hoare ◽

...

Keyword(s):

Porphyromonas Gingivalis ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Apical Periodontitis ◽

Healthy Individuals ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Apical Lesions ◽

Total Bacteria

Apical periodontitis is an inflammatory disease of microbial etiology. It has been suggested that endodontic bacterial DNA might translocate to distant organs via blood vessels, but no studies have been conducted. We aimed first to explore overall extraradicular infection, as well as specifically by Porphyromonas spp; and their potential to translocate from infected root canals to blood through peripheral blood mononuclear cells. In this cross-sectional study, healthy individuals with and without a diagnosis of apical periodontitis with an associated apical lesion of endodontic origin (both, symptomatic and asymptomatic) were included. Apical lesions (N=64) were collected from volunteers with an indication of tooth extraction. Intracanal samples (N=39) and respective peripheral blood mononuclear cells from apical periodontitis (n=14) individuals with an indication of endodontic treatment, as well as from healthy individuals (n=14) were collected. The detection frequencies and loads (DNA copies/mg or DNA copies/μL) of total bacteria, Porphyromonas endodontalis and Porphyromonas gingivalis were measured by qPCR. In apical lesions, the detection frequencies (%) and median bacterial loads (DNA copies/mg) respectively were 70.8% and 4521.6 for total bacteria; 21.5% and 1789.7 for Porphyromonas endodontalis; and 18.4% and 1493.9 for Porphyromonas gingivalis. In intracanal exudates, the detection frequencies and median bacterial loads respectively were 100% and 21089.2 (DNA copies/μL) for total bacteria, 41% and 8263.9 for Porphyromonas endodontalis; and 20.5%, median 12538.9 for Porphyromonas gingivalis. Finally, bacteria were detected in all samples of peripheral blood mononuclear cells including apical periodontitis and healthy groups, though total bacterial loads (median DNA copies/μL) were significantly higher in apical periodontitis (953.6) compared to controls (300.7), p<0.05. Porphyromonas endodontalis was equally detected in both groups (50%), but its bacterial load tended to be higher in apical periodontitis (262.3) than controls (158.8), p>0.05; Porphyromonas gingivalis was not detected. Bacteria and specifically Porphyromonas spp. were frequently detected in endodontic canals and apical lesions. Also, total bacteria and Porphyromonas endodontalis DNA were detected in peripheral blood mononuclear cells, supporting their plausible role in bacterial systemic translocation.

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MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

10.21203/rs.2.9964/v2 ◽

2019 ◽

Author(s):

Tao Huang ◽

Jun Zhang ◽

Wujian Ke ◽

Xiaohui Zhang ◽

Wentao Chen ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Cell Function ◽

Immune Cell ◽

Treponema Pallidum ◽

Target Sequence ◽

Healthy Individuals ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Abstract Background Treponema pallidum ( T. pallidum ) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum . Methods In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. Results A total of 89 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states ( P <0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals. Conclusions This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.

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Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects

Genes & Nutrition ◽

10.1007/s12263-014-0390-x ◽

2014 ◽

Vol 9 (3) ◽

Cited By ~ 16

Author(s):

Raffaella Canali ◽

Lucia Natarelli ◽

Guido Leoni ◽

Elena Azzini ◽

Raffaella Comitato ◽

...

Keyword(s):

Gene Expression ◽

Pilot Study ◽

Vitamin C ◽

Peripheral Blood Mononuclear Cells ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Inflammatory Stimulus ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Vitamin C Supplementation

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RNA-Seq Transcriptome Analysis Reveals Long Terminal Repeat Retrotransposon Modulation in Human Peripheral Blood Mononuclear Cells after In Vivo Lipopolysaccharide Injection

Journal of Virology ◽

10.1128/jvi.00587-20 ◽

2020 ◽

Vol 94 (19) ◽

Author(s):

Maria Paola Pisano ◽

Olivier Tabone ◽

Maxime Bodinier ◽

Nicole Grandi ◽

Julien Textoris ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Ltr Retrotransposon ◽

Ltr Retrotransposons ◽

Rna Seq ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

ABSTRACT Human endogenous retroviruses (HERVs) and mammalian apparent long terminal repeat (LTR) retrotransposons (MaLRs) are retroviral sequences that integrated into germ line cells millions of years ago. Transcripts of these LTR retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. Here, we focused on the HERV/MaLR expression and modulation in a scenario of immune system activation. We used a public data set of human peripheral blood mononuclear cells (PBMCs) RNA-Seq from 15 healthy participants to a clinical trial before and after exposure to lipopolysaccharide (LPS), for which we established an RNA-Seq workflow for the identification of expressed and modulated cellular genes and LTR retrotransposon elements. IMPORTANCE We described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4% of the LTR retrotransposon loci were expressed and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERV and MaLR loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci as differentially expressed, checking their genomic context of insertion and observing a general colocalization with genes that are involved and modulated in the immune response, as a consequence of LPS stimulation. The analyses of HERV and MaLR expression and modulation show that these LTR retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR retrotransposons and the immune host response.

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