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1.
J Perinat Med ; 52(7): 730-736, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-38949076

ABSTRACT

OBJECTIVES: There is controversial evidence that acidification of vaginal pH may increase the efficacy of vaginal prostaglandins in labor induction, with research being mainly focused on misoprostol. This study aims to evaluate the impact of this intervention on the progress of labor induction with dinoprostone (PGE2) vaginal tablet. METHODS: This double-blind, parallel-group, randomized study was conducted between October 2021 and December 2022 at Alexandra General Hospital, Athens, Greece. A total of 230 women with singleton, full term pregnancy that were scheduled for labor induction were randomly divided into two groups: Group A, who received acidic vaginal wash (5 % acetic acid) and Group B, who received a normal saline vaginal wash. Afterwards, participants received a vaginal tablet of 3 mg dinoprostone every 6 h (maximum two doses). RESULTS: There were no statistically significant differences in mode of delivery, duration of different labor stages, Bishop score changes and possible complications. Participants in the acidification group needed less often labor augmentation with oxytocin and epidural anesthesia (p=0.03). CONCLUSIONS: Vaginal acidification seems to have no effect on the efficacy of the dinoprostone vaginal tablet. Even though it may reduce the need for oxytocin augmentation, there is no apparent benefit on clinical outcomes, such as reduction in cesarean section rates or shorter labor duration. Future research is necessary in order to validate these findings.


Subject(s)
Dinoprostone , Labor, Induced , Oxytocics , Humans , Female , Pregnancy , Dinoprostone/administration & dosage , Labor, Induced/methods , Adult , Oxytocics/administration & dosage , Hydrogen-Ion Concentration , Double-Blind Method , Administration, Intravaginal , Vagina/drug effects , Young Adult
2.
Arch Gynecol Obstet ; 310(3): 1343-1354, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39008086

ABSTRACT

PURPOSE: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. METHODS: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966-2041), Scopus (2004-2024), Clinicaltrials.gov (2008-2024), EMBASE (1980-2024), Cochrane Central Register of Controlled Trials CENTRAL (1999-2024) and Google Scholar (2004-2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. RESULTS: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). CONCLUSION: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies.


Subject(s)
Cell-Free Nucleic Acids , Pregnancy Outcome , Humans , Pregnancy , Female , Cell-Free Nucleic Acids/blood , Cell-Free Nucleic Acids/analysis , Pregnancy Complications/diagnosis , Pregnancy Complications/blood , Diabetes, Gestational/diagnosis , Diabetes, Gestational/blood , Infant, Small for Gestational Age , Premature Birth/diagnosis , Noninvasive Prenatal Testing , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/blood
3.
Curr Top Microbiol Immunol ; 436: 165-196, 2022.
Article in English | MEDLINE | ID: mdl-36243844

ABSTRACT

Macrophages display an array of activation phenotypes depending on the activation signal and the cellular microenvironment. The type and magnitude of the response depend on signaling molecules as well as on the epigenetic and metabolic status of the cells at the time of activation. The AKT family of kinases consists of three isoforms encoded by independent genes possessing similar functions and structures. Generation of research tools such as isoform-specific gene deletion mutant mice and cells and isoform-specific antibodies has allowed us to understand the role of each kinase isoform in macrophage activation and homeostasis. This chapter discusses the current evidence on the role of AKT kinases in macrophage activation, polarization, and homeostasis, highlighting the gaps in knowledge and future challenges in the field.


Subject(s)
Macrophage Activation , Proto-Oncogene Proteins c-akt , Animals , Macrophages , Mice , Protein Isoforms/genetics , Protein Isoforms/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
4.
Mar Drugs ; 21(2)2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36827120

ABSTRACT

The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (1-4) and a 5-membered one (5), 15 sesquiterpenes, including seven lauranes (6-12), one cuparane (13), one seco-laurane (14), one snyderane (15), two chamigranes (16, 17), two rearranged chamigranes (18, 19) and one aristolane (20), as well as a tricyclic diterpene (21) and a chlorinated fatty acid derivative (22). Among them, compounds 1-3, 5, 7, 8, 10, 11 and 14 are new natural products. The structures and the relative configurations of the isolated natural products have been established based on extensive analysis of their NMR and MS data, while the absolute configuration of maneonenes F (1) and G (2) was determined on the basis of single-crystal X-ray diffraction analysis. The anti-inflammatory activity of compounds 1, 2, 4-8, 10, 12-16, 18 and 20-22 was evaluated by measuring suppression of nitric oxide (NO) release in TLR4-activated RAW 264.7 macrophages in culture. All compounds, except 6, exhibited significant anti-inflammatory activity. Among them, metabolites 1, 4 and 18 did not exhibit any cytostatic activity at the tested concentrations. The most prominent anti-inflammatory activity, accompanied by absence of cytostatic activity at the same concentration, was exerted by compounds 5 and 18, with IC50 values of 3.69 µM and 3.55 µΜ, respectively.


Subject(s)
Biological Products , Cytostatic Agents , Laurencia , Sesquiterpenes , Laurencia/chemistry , Molecular Structure , Indian Ocean , Anti-Inflammatory Agents/chemistry , Sesquiterpenes/chemistry
5.
Mar Drugs ; 21(6)2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37367668

ABSTRACT

Obesity and type 2 diabetes are characterized by low-grade systemic inflammation and glucose intolerance, which can be partially controlled with nutritional interventions. Protein-containing nutritional supplements possess health-promoting benefits. Herein, we examined the effect of dietary supplementation with protein hydrolysates derived from fish sidestreams on obesity and diabetes, utilizing a mouse model of High-Fat Diet-induced obesity and type 2 diabetes. We examined the effect of protein hydrolysates from salmon and mackerel backbone (HSB and HMB, respectively), salmon and mackerel heads (HSH and HMH, respectively), and fish collagen. The results showed that none of the dietary supplements affected weight gain, but HSH partially suppressed glucose intolerance, while HMB and HMH suppressed leptin increase in the adipose tissue. We further analyzed the gut microbiome, which contributes to the metabolic disease implicated in the development of type 2 diabetes, and found that supplementation with selected protein hydrolysates resulted in distinct changes in gut microbiome composition. The most prominent changes occurred when the diet was supplemented with fish collagen since it increased the abundance of beneficial bacteria and restricted the presence of harmful ones. Overall, the results suggest that protein hydrolysates derived from fish sidestreams can be utilized as dietary supplements with significant health benefits in the context of type 2 diabetes and diet-induced changes in the gut microbiome.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Glucose Intolerance , Insulin Resistance , Mice , Animals , Glucose Intolerance/metabolism , Protein Hydrolysates/pharmacology , Protein Hydrolysates/metabolism , Mice, Obese , Diabetes Mellitus, Type 2/metabolism , Obesity/drug therapy , Obesity/etiology , Obesity/metabolism , Adipose Tissue/metabolism , Dietary Supplements , Diet, High-Fat/adverse effects , Collagen/metabolism , Mice, Inbred C57BL
6.
Mar Drugs ; 19(5)2021 May 11.
Article in English | MEDLINE | ID: mdl-34064922

ABSTRACT

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dietary Supplements , Fishes , Gastrointestinal Microbiome/drug effects , Hypoglycemic Agents/pharmacology , Obesity , Tissue Extracts/pharmacology , Abdominal Fat/drug effects , Animals , Body Weight/drug effects , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/complications , Diet, High-Fat/adverse effects , Dietary Supplements/microbiology , Disease Models, Animal , Female , Glucose Intolerance/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Leptin/metabolism , Mice, Inbred C57BL , Obesity/chemically induced , Obesity/complications , Tissue Extracts/isolation & purification , Tissue Extracts/therapeutic use
7.
Mar Drugs ; 19(6)2021 May 28.
Article in English | MEDLINE | ID: mdl-34071180

ABSTRACT

Inflammatory bowel disease is characterized by extensive intestinal inflammation, and therapies against the disease target suppression of the inflammatory cascade. Nutrition has been closely linked to the development and suppression of inflammatory bowel disease, which to a large extent is attributed to the complex immunomodulatory properties of nutrients. Diets containing fish have been suggested to promote health and suppress inflammatory diseases. Even though most of the health-promoting properties of fish-derived nutrients are attributed to fish oil, the potential health-promoting properties of fish protein have not been investigated. Fish sidestreams contain large amounts of proteins, currently unexploited, with potential anti-inflammatory properties, and may possess additional benefits through bioactive peptides and free amino acids. In this project, we utilized fish protein hydrolysates, based on mackerel and salmon heads and backbones, as well as flounder skin collagen. Mice fed with a diet supplemented with different fish sidestream-derived protein hydrolysates (5% w/w) were exposed to the model of DSS-induced colitis. The results show that dietary supplements containing protein hydrolysates from salmon heads suppressed chemically-induced colitis development as determined by colon length and pro-inflammatory cytokine production. To evaluate colitis severity, we measured the expression of different pro-inflammatory cytokines and chemokines and found that the same supplement suppressed the pro-inflammatory cytokines IL-6 and TNFα and the chemokines Cxcl1 and Ccl3. We also assessed the levels of the anti-inflammatory cytokines IL-10 and Tgfb and found that selected protein hydrolysates induced their expression. Our findings demonstrate that protein hydrolysates derived from fish sidestreams possess anti-inflammatory properties in the model of DSS-induced colitis, providing a novel underexplored source of health-promoting dietary supplements.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis/drug therapy , Fishes , Protein Hydrolysates/therapeutic use , Waste Products , Animals , Anti-Inflammatory Agents/pharmacology , Colitis/chemically induced , Colitis/genetics , Colitis/pathology , Colon/drug effects , Colon/immunology , Colon/pathology , Cytokines/blood , Cytokines/genetics , Dextran Sulfate , Dietary Supplements , Female , Food Industry , Mice, Inbred C57BL , Protein Hydrolysates/pharmacology
8.
Mar Drugs ; 19(7)2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34356821

ABSTRACT

Restoring homeostasis following tissue damage requires a dynamic and tightly orchestrated sequence of molecular and cellular events that ensure repair and healing. It is well established that nutrition directly affects skin homeostasis, while malnutrition causes impaired tissue healing. In this study, we utilized fish sidestream-derived protein hydrolysates including fish collagen as dietary supplements, and investigated their effect on the skin repair process using a murine model of cutaneous wound healing. We explored potential differences in wound closure and histological morphology between diet groups, and analyzed the expression and production of factors that participate in different stages of the repair process. Dietary supplementation with fish sidestream-derived collagen alone (Collagen), or in combination with a protein hydrolysate derived from salmon heads (HSH), resulted in accelerated healing. Chemical analysis of the tested extracts revealed that Collagen had the highest protein content and that HSH contained the great amount of zinc, known to support immune responses. Indeed, tissues from mice fed with collagen-containing supplements exhibited an increase in the expression levels of chemokines, important for the recruitment of immune cells into the damaged wound region. Moreover, expression of a potent angiogenic factor, vascular endothelial growth factor-A (VEGF-A), was elevated followed by enhanced collagen deposition. Our findings suggest that a 5%-supplemented diet with marine collagen-enriched supplements promotes tissue repair in the model of cutaneous wound healing, proposing a novel health-promoting use of fish sidestreams.


Subject(s)
Collagen/drug effects , Protein Hydrolysates/pharmacology , Salmon , Wound Healing/drug effects , Animals , Chemokines/metabolism , Dietary Supplements , Male , Mice , Mice, Inbred C57BL , Models, Animal , Protein Hydrolysates/administration & dosage
9.
Mar Drugs ; 18(11)2020 10 24.
Article in English | MEDLINE | ID: mdl-33114361

ABSTRACT

Inflammation is part of the organism's response to deleterious stimuli, such as pathogens, damaged cells, or irritants. Macrophages orchestrate the inflammatory response obtaining different activation phenotypes broadly defined as M1 (pro-inflammatory) or M2 (homeostatic) phenotypes, which contribute to pathogen elimination or disease pathogenesis. The type and magnitude of the response of macrophages are shaped by endogenous and exogenous factors and can be affected by nutrients or therapeutic agents. Multiple studies have shown that natural products possess immunomodulatory properties and that marine algae contain products with such action. We have previously shown that disulfides isolated from Dictyopteris membranacea suppress nitric oxide (NO) production from activated macrophages, suggesting potential anti-inflammatory actions. In this study, we investigated the anti-inflammatory mechanism of action of bis(5-methylthio-3-oxo-undecyl) disulfide (1), 5-methylthio-1-(3-oxo-undecyl) disulfanylundecan-3-one (2) and 3-hexyl-4,5-dithiocycloheptanone (3). Our results showed that all three compounds inhibited M1 activation of macrophages by down regulating the production of pro-inflammatory cytokines TNFα, IL-6 and IL-12, suppressed the expression of the NO converting enzyme iNOS, and enhanced expression of the M2 activation markers Arginase1 and MRC1. Moreover, disulfides 1 and 2 suppressed the expression of glucose transporters GLUT1 and GLUT3, suggesting that compounds 1 and 2 may affect cell metabolism. We showed that this was due to AKT/MAPK/ERK signaling pathway modulation and specifically by elevated AKT phosphorylation and MAPK/ERK signal transduction reduction. Hence, disulfides 1-3 can be considered as potent candidates for the development of novel anti-inflammatory molecules with homeostatic properties.


Subject(s)
Disulfides/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Macrophages/drug effects , Mitogen-Activated Protein Kinase Kinases/metabolism , Phaeophyceae/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Disulfides/chemistry , Extracellular Signal-Regulated MAP Kinases/genetics , Gene Expression Regulation/drug effects , Macrophage Activation , Mice , Mitogen-Activated Protein Kinase Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , RAW 264.7 Cells
10.
J Immunol ; 198(3): 1297-1307, 2017 02 01.
Article in English | MEDLINE | ID: mdl-28011933

ABSTRACT

During macrophage activation, expression of IL-1R-associated kinase (IRAK)-M is induced to suppress TLR-mediated responses and is a hallmark of endotoxin tolerance. Endotoxin tolerance requires tight regulation of genes occurring at the transcriptional and epigenetic levels. To identify novel regulators of IRAK-M, we used RAW 264.7 macrophages and performed a targeted RNA interference screen of genes encoding chromatin-modifying enzymes, signaling molecules, and transcription factors involved in macrophage activation. Among these, the transcription factor CCAAT/enhancer binding protein (C/EBP)ß, known to be involved in macrophage inactivation, was necessary for the induction of IRAK-M expression. Chromatin immunoprecipitation showed that C/EBPß was recruited to the IRAK-M promoter following LPS stimulation and was indispensable for IRAK-M transcriptional activation. Among histone 3-modifying enzymes, our screen showed that knockdown of the histone 3 lysine 27 (H3K27) methyltransferase and part of the polycomb recessive complex 2, enhancer of Zeste 2, resulted in IRAK-M overexpression. In contrast, knockdown of the H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat X chromosome suppressed the induction of IRAK-M in response to LPS stimulation. Accordingly, we demonstrated that H3K27 on the IRAK-M promoter is trimethylated in unstimulated cells and that this silencing epigenetic mark is removed upon LPS stimulation. Our data propose a mechanism for IRAK-M transcriptional regulation according to which, in the naive state, polycomb recessive complex 2 repressed the IRAK-M promoter, allowing low levels of expression; following LPS stimulation, the IRAK-M promoter is derepressed, and transcription is induced to allow its expression.


Subject(s)
Epigenesis, Genetic , Interleukin-1 Receptor-Associated Kinases/genetics , Macrophages/metabolism , Transcription, Genetic , Animals , CCAAT-Enhancer-Binding Protein-beta/physiology , Cells, Cultured , Dealkylation , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/physiology , Promoter Regions, Genetic
11.
Mar Drugs ; 17(2)2019 Feb 02.
Article in English | MEDLINE | ID: mdl-30717366

ABSTRACT

Macrophages are central mediators of inflammation, orchestrating the inflammatory response through the production of cytokines and nitric oxide. Macrophages obtain pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, which can be modulated by soluble factors, including natural products. Despite the crucial protective role of inflammation, chronic or deregulated inflammation can lead to pathological states, such as autoimmune diseases, metabolic disorders, cardiovascular diseases, and cancer. In this case, we studied the anti-inflammatory activity of neorogioltriol (1) in depth and identified two structurally related diterpenes, neorogioldiol (2), and O11,15-cyclo-14-bromo-14,15-dihydrorogiol-3,11-diol (3), with equally potent activity. We investigated the mechanism of action of metabolites 1⁻3 and found that all three suppressed macrophage activation and promoted an M2-like anti-inflammatory phenotype by inducing expression of Arginase1, MRC1, IRAK-M, the transcription factor C/EBPß, and the miRNA miR-146a. In addition, they suppressed iNOS induction and nitric oxide production. Importantly, treatment of mice with 2 or 3 suppressed DSS-induced colitis by reducing tissue damage and pro-inflammatory cytokine production. Thus, all these three diterpenes are promising lead molecules for the development of anti-inflammatory agents targeting macrophage polarization mechanisms.


Subject(s)
Diterpenes/chemistry , Diterpenes/pharmacology , Inflammatory Bowel Diseases/drug therapy , Laurencia/chemistry , Macrophages/drug effects , Animals , Cell Proliferation , Dextran Sulfate/toxicity , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/pathology , Macrophages/classification , Mice , Mice, Inbred C57BL , Molecular Structure , RAW 264.7 Cells
12.
Mar Drugs ; 17(11)2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31731724

ABSTRACT

Thuwalallenes A-E (1-3, 5 and 8) and thuwalenynes A-C (4, 6, 7), new C15 acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol (11) were isolated from the organic extract of a population of the red alga Laurencia sp., collected at Rose Reef off the village of Thuwal in the Red Sea waters of the Kingdom of Saudi Arabia. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data. Compounds 1-6, 8, 10 and 11 were evaluated for their anti-inflammatory activity by quantifying nitric oxide (NO) release in response to TLR4 stimulation in macrophages. Besides compound 4 that did not exhibit any activity, all other tested metabolites inhibited NO production from activated macrophages. Among them, thyrsiferol (10) and 23-acetylthyrsiferol (11) displayed activity with IC50 values in the low nM scale without cytotoxicity.


Subject(s)
Acetogenins/chemistry , Anti-Inflammatory Agents/chemistry , Biological Products/chemistry , Laurencia/chemistry , Animals , Cell Line , Indian Ocean , Mice , RAW 264.7 Cells , Saudi Arabia
13.
J Cell Physiol ; 233(9): 6495-6507, 2018 09.
Article in English | MEDLINE | ID: mdl-29574768

ABSTRACT

Macrophages respond to noxious stimuli and contribute to inflammatory responses by eliminating pathogens or damaged tissue and maintaining homeostasis. Response to activation signals and maintenance of homeostasis require tight regulation of genes involved in macrophage activation and inactivation processes, as well as genes involved in determining their polarization state. Recent evidence has revealed that such regulation occurs through histone modifications that render inflammatory or polarizing gene promoters accessible to transcriptional complexes. Thus, inflammatory and anti-inflammatory genes are regulated by histone acetylation and methylation, determining their activation state. Herein, we review the current knowledge on the role of histone modifying enzymes (acetyltransferases, deacetylases, methyltransferases, and demethylases) in determining the responsiveness and M1 or M2 polarization of macrophages. The contribution of these enzymes in the development of inflammatory diseases is also presented.


Subject(s)
Histones/metabolism , Inflammation/metabolism , Macrophages/metabolism , Acetylation , Animals , Humans , Methylation
14.
Immunol Cell Biol ; 95(3): 316-320, 2017 03.
Article in English | MEDLINE | ID: mdl-27779180

ABSTRACT

Granzyme B-expressing (GrB+) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB+ B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts. When investigating GrB+ B cells in different compartments, levels were highest in blood, spleen and bone marrow, but considerably lower in lymph nodes and tonsils. Analysis of expression of various surface markers on this particular B-cell subset in SIV-infected macaques revealed differences between the phenotype in macaques and in humans. GrB+ B cells in SIV-infected rhesus macaques exhibit an elevated expression of CD5, CD10, CD25 and CD27, while expression of CD19, CD185 and HLA-DR is reduced. In contrast to human GrB+ B cells, we did not observe a significantly increased expression of CD43 and CD86. B-cell receptor stimulation in combination with IL-21 of purified B cells from healthy animals led to the induction of GrB expression. Furthermore, initial functional analyses indicated a regulatory role on T-cell proliferation. Overall, our data pave the way for longitudinal analyses including studies on the functionality of GrB+ B cells in the nonhuman primate model for AIDS.


Subject(s)
B-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/immunology , Granzymes/metabolism , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/physiology , Viral Load/immunology , Animals , CD4 Lymphocyte Count , Disease Progression , Female , Humans , Interleukin-10/metabolism , Macaca mulatta , Male
15.
J Med Primatol ; 46(4): 144-148, 2017 08.
Article in English | MEDLINE | ID: mdl-28748664

ABSTRACT

Hallmarks of SIV infection are early depletion of gut CD4 T cells and diminished intestinal integrity. Comprehensive studies on colon biopsies of SIV-infected macaques efficiently controlling infection revealed that in contrast to viremic and failing controllers, elite controllers show preserved CD4 T cells, and low viral load, apoptosis, and inflammation.


Subject(s)
Colon/immunology , Macaca mulatta , Simian Acquired Immunodeficiency Syndrome/immunology , Animals , Apoptosis , CD4 Lymphocyte Count , Colon/anatomy & histology , Colon/virology , India , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/physiology
16.
J Med Primatol ; 45(3): 139-46, 2016 06.
Article in English | MEDLINE | ID: mdl-27221549

ABSTRACT

BACKGROUND: Common marmosets are extensively used in immunological and pharmacological research, and the usage of methods such as flow cytometry gain increasing importance. METHODS: Using multicolor flow cytometry cross-reactivity of monoclonal antibodies with cells of common marmosets was analyzed. Furthermore, frequencies of immune cells and immunological parameters were assessed in healthy common marmosets. RESULTS: A total of 97 clones of monoclonal antibodies raised against CD markers, chemokine receptors, and miscellaneous markers were tested. Additionally, baseline frequencies of different innate and adaptive immune cells as well as certain parameters, such as activation and memory T-cell and B-cell distribution, are provided. CONCLUSION: Our study gives an extended overview of cross-reactive antibodies for flow cytometric analysis of immune cells as well as baseline values for different immune parameters in healthy common marmosets.


Subject(s)
Antibodies, Monoclonal/immunology , Callithrix/immunology , Dendritic Cells/immunology , Leukocytes/immunology , Animals , Cross Reactions , Flow Cytometry
17.
J Nat Prod ; 79(3): 584-9, 2016 Mar 25.
Article in English | MEDLINE | ID: mdl-26943727

ABSTRACT

Six new (1, 2, and 4-7) and two previously reported (3 and 8) disulfides, along with 4-butyl-2,6-cycloheptadienone, γ-tocopherol, and δ-tocopherol, were isolated from an organic extract of the brown alga Dictyopteris membranacea, collected at Gerolimenas Bay, Greece. The structure elucidation of the isolated natural products was based on analysis of their spectroscopic data. Compounds 1, 3-6, and 8 were evaluated for their antibacterial and anti-inflammatory activities. None of the compounds displayed antibacterial activity against two resistant strains of Staphylococcus aureus and one strain of Escherichia coli. In contrast, metabolite 5 was able to cause strong inhibition of NO production with an IC50 value of 3.8 µM using an LPS stimulation assay.


Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Disulfides/isolation & purification , Disulfides/pharmacology , Phaeophyceae/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents/chemistry , Disulfides/chemistry , Escherichia coli/drug effects , Greece , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Microbial Sensitivity Tests , Molecular Structure , Nitric Oxide/biosynthesis , Nuclear Magnetic Resonance, Biomolecular , Staphylococcus aureus/drug effects , Tocopherols
18.
J Med Primatol ; 44(5): 253-62, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26227257

ABSTRACT

BACKGROUND: T-follicular helper (T(FH)) cells are an important population in lymph nodes (LNs) contributing to the generation of highly specific B cells. For SIV studies in rhesus macaques (RM), analysis of LN is necessary, but restricted due to invasive sampling. We applied the minimally invasive LN fine-needle aspiration (LN-FNA) and examined dynamics of T(FH) cells during SIV infection. MATERIALS AND METHODS: LN-FNA and LN resection were carried out on uninfected RM. Lymphocytes were analyzed by flow cytometry. Additionally, cells obtained by LN-FNA over time from SIV-infected RM were analyzed. RESULTS: Percentages of lymphocyte subsets were similar in LN aspirates and whole LNs. Analysis of LN aspirates from SIV-infected RM demonstrated a decrease of CD4(+) T cells, while T(FH) cell frequencies increased over time and correlated significantly with plasma viral load. CONCLUSIONS: By applying LN-FNA, we showed that T(FH) cell expansion in chronic SIV infection is associated with viral load.


Subject(s)
Lymph Nodes/immunology , Lymphocyte Subsets/immunology , Macaca mulatta , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/physiology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Biopsy, Fine-Needle , Female , Male , Simian Acquired Immunodeficiency Syndrome/virology , Viral Load
19.
J Ovarian Res ; 17(1): 120, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824584

ABSTRACT

BACKGROUND: The common marmoset, Callithrix jacchus, is an invaluable model in biomedical research. Its use includes genetic engineering applications, which require manipulations of oocytes and production of embryos in vitro. To maximize the recovery of oocytes suitable for embryo production and to fulfil the requirements of the 3R principles to the highest degree possible, optimization of ovarian stimulation protocols is crucial. Here, we compared the efficacy of two hormonal ovarian stimulation approaches: 1) stimulation of follicular growth with hFSH followed by triggering of oocyte maturation with hCG (FSH + hCG) and 2) stimulation with hFSH only (FSH-priming). METHODS: In total, 14 female marmosets were used as oocyte donors in this study. Each animal underwent up to four surgical interventions, with the first three performed as ovum pick-up (OPU) procedures and the last one being an ovariohysterectomy (OvH). In total, 20 experiments were carried out with FSH + hCG stimulation and 18 with FSH-priming. Efficacy of each stimulation protocol was assessed through in vitro maturation (IVM), in vitro fertilization (IVF) and embryo production rates. RESULTS: Each study group consisted of two subgroups: the in vivo matured oocytes and the oocytes that underwent IVM. Surprisingly, in the absence of hCG triggering some of the oocytes recovered were at the MII stage, moreover, their number was not significantly lower compared to FSH + hCG stimulation (2.8 vs. 3.9, respectively (ns)). While the IVM and IVF rates did not differ between the two stimulation groups, the IVF rates of in vivo matured oocytes were significantly lower compared to in vitro matured ones in both FSH-priming and FSH + hCG groups. In total, 1.7 eight-cell embryos/experiment (OPU) and 2.1 eight-cell embryos/experiment (OvH) were obtained after FSH + hCG stimulation vs. 1.8 eight-cell embryos/experiment (OPU) and 5.0 eight-cell embryos/experiment (OvH) following FSH-priming. These numbers include embryos obtained from both in vivo and in vitro matured oocytes. CONCLUSION: A significantly lower developmental competence of the in vivo matured oocytes renders triggering of the in vivo maturation with hCG as a part of the currently used FSH-stimulation protocol unnecessary. In actual numbers, between 1 and 7 blastocysts were obtained following each FSH-priming. In the absence of further studies, FSH-priming appears superior to FSH + hCG stimulation in the common marmoset under current experimental settings.


Subject(s)
Callithrix , Chorionic Gonadotropin , Fertilization in Vitro , Follicle Stimulating Hormone , In Vitro Oocyte Maturation Techniques , Oocytes , Ovulation Induction , Animals , Female , Ovulation Induction/methods , In Vitro Oocyte Maturation Techniques/methods , Oocytes/drug effects , Chorionic Gonadotropin/pharmacology , Follicle Stimulating Hormone/pharmacology , Fertilization in Vitro/methods
20.
J Clin Med ; 13(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38541892

ABSTRACT

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines.

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