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Journal of Pediatric Hematology/oncology Jul 2020Emerging data have suggested that sirolimus may be a treatment option for complicated vascular anomalies (VAs). The present study aimed to investigate the immunologic...
Emerging data have suggested that sirolimus may be a treatment option for complicated vascular anomalies (VAs). The present study aimed to investigate the immunologic effects of sirolimus treatment for 6 months in patients with VAs. Blood samples obtained from the patients enrolled in 2 multicenter studies to investigate the efficacy of sirolimus for VAs before and after sirolimus treatment for 6 months were used. Data for total white blood cell count, absolute lymphocyte count, serum immunoglobulins (Igs) levels (IgG, IgA, IgM), lymphocyte proliferation assays with mitogens including phytohemagglutinin and concanavalin A, and flow cytometric analysis of lymphocyte subsets were evaluated. A total of 18 patients with VAs receiving sirolimus treatment were included in the study. Comparisons of white blood cell, absolute lymphocyte count, IgG, IgA, IgM, and reaction rates of phytohemagglutinin and concanavalin A revealed no significant differences before and after treatment. No significant differences were observed in the absolute counts of lymphocyte subtypes before and after treatment, except for regulatory T-cell counts, which were significantly decreased after treatment. Severe infections were not observed during sirolimus treatment. The immunologic parameters assessed in the present study were hardly affected by sirolimus treatment for 6 months in patients with VAs.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Infant; Lymphocytes; Male; Prognosis; Sirolimus; T-Lymphocytes, Regulatory; Vascular Malformations; Young Adult
PubMed: 31743321
DOI: 10.1097/MPH.0000000000001650 -
Current Topics in Medicinal Chemistry 2021Obesity has become a worldwide health problem. It triggers additional co-morbidities like cardiovascular diseases, cancer, depression, sleep disorders, gastrointestinal... (Review)
Review
Obesity has become a worldwide health problem. It triggers additional co-morbidities like cardiovascular diseases, cancer, depression, sleep disorders, gastrointestinal problems and many more. Excess accumulation of fat in obesity could be caused by many factors like sedentary lifestyle, consumption of high-fat diet, genetic predisposition, etc. Imbalanced energy metabolism i.e., greater energy consumption than utilisation, invariably underlies obesity. Considering the high prevalence and continuous, uncontrolled increase of this major public health issue, there is an urgent need to find appropriate therapeutic agents with minimal or no side effects. The high prevalence of obesity in recent years has led to a surge in the number of drugs available in the market that claim to control obesity. Although there is a long list of medicines and management strategies that are available, selecting the right therapeutic intervention and feasible management of obesity is a challenge. Several phytochemicals like hydroxycitric acid, flavonoids, tannins, anthocyanins, phytohaemagglutinin, thymoquinone and epigallocatechin gallate have been shown to possess promising anti-obesity properties. However, studies providing information on how various phytochemicals exert their anti-obesity effects are inadequate. This calls for more experimentation in this less explored area of research. Additionally, the complication of obesity arises when it is a result of multiple factors and associated with a number of co-morbidities. In order to handle such complexities, combinatorial therapeutic interventions become effective. In this review, we have described the medicinal chemistry of different highly effective phytochemicals which can be used in the effective treatment and management of obesity.
Topics: Adipokines; Animals; Anthocyanins; Anti-Obesity Agents; Benzoquinones; Catechin; Citrates; Drug Discovery; Drug Therapy, Combination; Energy Metabolism; Enzyme Inhibitors; Flavonoids; Humans; Lipids; Obesity; Phytochemicals; Phytohemagglutinins; Plant Extracts; Plants; Signal Transduction; Tannins
PubMed: 33676390
DOI: 10.2174/1568026621666210305101804 -
Frontiers in Immunology 2021In mammals, Interleukin-17 cytokine family plays critical roles in both acute and chronic inflammatory responses. In fish species, three Interleukin-17A/F (IL-17A/F)...
In mammals, Interleukin-17 cytokine family plays critical roles in both acute and chronic inflammatory responses. In fish species, three Interleukin-17A/F (IL-17A/F) genes have been identified to be homologous to mammalian IL-17A and IL-17F, but little is known about their functional activity. In this study, _IL-17A/F1, 2 and 3 genes were cloned from yellow catfish () and they differed in protein structure and exon length, implying that they may have divergent bioactivity. Real-time quantitative PCR analyses revealed that three _IL-17A/F genes were highly expressed in blood and mucosal tissues (skin+mucus and gill) from healthy adult fish. The mRNA expressions of _IL-17A/F1, 2 and 3 genes were significantly up-regulated in the gill, skin+mucus, head kidney and spleen after challenge with and in the isolated peripheral blood leucocytes (PBLs) of yellow catfish after stimulation with phytohaemagglutinin (PHA), lipopolysaccharides (LPS), peptidoglycan (PGN) and polyinosinic-polycytidylic acid (Poly I:C). These results indicate that _IL-17A/F1, 2 and 3 genes may play a vital role in the regulation of immune against pathogens. Additionally, the recombinant (r) _IL-17A/F1, 2 and 3 proteins significantly induced the mRNA expressions of proinflammatory cytokines, chemokines and antibacterial peptides genes, and the r_IL-17A/F 2 and 3 proteins promoted phagocytosis of PBLs more powerfully than the r_IL-17A/F1. Furthermore, the r_IL-17A/F1, 2 and 3 proteins might activate the NF-κB and MAPK signal pathways by IL-17RA, ACT1, TRAF6, TRAF2, TRAF5 and TAK1, indicating that the three _IL-17A/F proteins may play different roles in promoting inflammatory response.
Topics: Animals; Catfishes; Fish Proteins; Head Kidney; Interleukin-17; Leukocytes; Lipopolysaccharides; Peptidoglycan; Phytohemagglutinins; Poly I-C; Spleen
PubMed: 34267744
DOI: 10.3389/fimmu.2021.626895 -
Molecules (Basel, Switzerland) Jul 2022Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined...
Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives - obtained during reactions of -substituted amidrazones with itaconic anhydride. Two groups of compounds, - and - differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives - and the anti-inflammatory activity of and - were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds and - was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives and - on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds - was studied in the sp. nematodes model. Most compounds (-) proved to be non-toxic to human PBMC. Derivatives - showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds and - significantly reduced the production of TNF-α and derivatives - decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound . Compounds and demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.
Topics: Anthelmintics; Anti-Infective Agents; Anti-Inflammatory Agents; Humans; Imidazoles; Leukocytes, Mononuclear; Sulfonamides; Thiophenes; Triazoles; Tumor Necrosis Factor-alpha
PubMed: 35889357
DOI: 10.3390/molecules27144488 -
Transplant Immunology Dec 2021Rejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating...
BACKGROUND/OBJECTIVES
Rejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants.
METHODS
This was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel.
RESULTS
Our study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance.
CONCLUSIONS
To our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.
Topics: Chemokines; Cross-Sectional Studies; Cytokines; Graft Rejection; Humans; Prospective Studies
PubMed: 34400246
DOI: 10.1016/j.trim.2021.101447 -
General and Comparative Endocrinology Jul 2023Steroid hormones (e.g. androgens [AN] and corticosterone [CORT]) modulate complex physiological functions such as reproduction, energy mobilization, metabolism, and...
Steroid hormones (e.g. androgens [AN] and corticosterone [CORT]) modulate complex physiological functions such as reproduction, energy mobilization, metabolism, and immunity. The effects of these steroids on immunocompetence and its metabolic costs can also be affected by fluctuations in environmental resource availability and other factors such as parasitism. To understand these possible interactions, we studied AN and CORT, immune response [swelling response to phytohemagglutinin (PHA) injection and bacterial killing ability (BKA)], parasite load, resting metabolic rate (RMR) and post-immune challenge (PHA injection) oxygen consumption rates during two different phases of the annual cycle of Rhinella jimi toads from the Brazilian semi-arid region (Caatinga), where environmental conditions are highly seasonal. We observed an increase in O consumption rates after both PHA and saline (control) injections, indicating a metabolic response to adverse stimuli rather than the immune challenge. Toads showing higher RMR and VO after the adverse stimuli (PHA/saline injections) had lower field AN and CORT plasma levels, suggesting these hormones might mediate a metabolic energy conservation strategy both at baseline levels and after adverse stimuli. Parasite load appear to constrain the metabolic response to PHA and saline injections. Additionally, individuals with a higher swelling response to PHA had higher field CORT plasma levels (particularly when males are breeding), which opposes the idea of a possible trade-off between reproductive activity and other physiological traits, indicating the immunoenhancing effects of elevated CORT at physiological levels. BKA did not show a seasonal variation or correlation with body condition or hormone levels, indicating that the immune surveillance mediated by the complement remains constant despite ecological and physiological changes.
Topics: Humans; Male; Animals; Bufonidae; Androgens; Seasons; Steroids; Immunity; Corticosterone
PubMed: 36931441
DOI: 10.1016/j.ygcen.2023.114263 -
Developmental and Comparative Immunology Sep 2021CC chemokine ligand 19 (CCL19) plays a key role in the regulation of immune responses including homeostasis, inflammation, and immune tolerance. In this study, two...
CC chemokine ligand 19 (CCL19) plays a key role in the regulation of immune responses including homeostasis, inflammation, and immune tolerance. In this study, two variants of CCL19 homologues (CCL19a2 and CCL19b) and CCR7 were investigated in grass carp Ctenopharyngodon idella. The three genes were widely expressed in immune tissues and could be modulated by stimulation with LPS, PHA and poly(I:C), and infection with Flavobacterium columnare and grass carp reovirus. In an in vitro chemotaxis assay, the recombinant CCL19a2 and CCL19b were active to promote the migration of HEK293 T cells expressing CCR7 and leucocytes isolated from the gills, head kidney and spleen. Moreover, their chemotactive effects were validated in vivo. We found that the cells recruited by CCL19a2 and CCl19b are mainly monocytes/macrophages expressing high levels of IL-1β, IFN-γ, colony stimulating factor 1 receptor (CSF1R) and MHC II. Our work suggests that CCL19a2 and CCl19b are involved in recruitment of antigen presenting cells in fish.
Topics: Animals; Antigen Presentation; Base Sequence; Carps; Cell Line; Cell Movement; Chemokine CCL19; Fish Diseases; Flavobacterium; Gills; HEK293 Cells; Head Kidney; Humans; Interferon-gamma; Interleukin-1beta; Leukocytes; Lipopolysaccharides; Macrophages; Monocytes; Phytohemagglutinins; Poly I-C; Receptors, CCR7; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Reoviridae; Sequence Analysis, DNA; Spleen
PubMed: 33965447
DOI: 10.1016/j.dci.2021.104127 -
Frontiers in Immunology 2023Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and...
INTRODUCTION
Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and neonatal immune function is still poorly characterized. Here, we investigate the relationship between maternal and neonatal immune function, and identify factors affecting the association between maternal and child cytokine secretion.
METHODS
In the French prospective cohort SEPAGES, blood samples were obtained from pregnant women (n=322) at gestational week 20 ± 4 and from their child at birth (n=156). Maternal and cord blood cytokine and chemokine (CK) levels were measured at baseline in all subjects and after T cell or dendritic cell activation with phytohemagglutinin or R848 (in total 29 and 27 measures in maternal and cord blood samples, respectively). Associations between environmental, individual factors and CK level were estimated by linear regression modeling. The maternal-cord blood CK relations were assessed by Pearson correlation and regression models.
RESULTS
We observed that pregnant women and neonates displayed specific CK secretion profiles in the innate and adaptive compartments at baseline and upon activation. Activation of T cells in cord blood induced high levels of IL-2, but low levels of IFNγ, IL-13 or IL-10, in comparison to maternal blood samples. Elsewhere, neonatal innate immune responses were characterized by low production of IFNα, while productions of IL-1β, IL-6, IL-8, IL-10 and TNFα were higher than maternal responses. Strong correlations were observed between most CK after activation in maternal and cord blood samples. Strikingly, a statistical association between global mother and child cytokine profiles was evidenced. Correlations were observed between some individual CK of pregnant women and their children, both at baseline (MCP1, RANTES) and after activation with R848 (IL-6, IL-8 and IL-10). We looked for factors which could influence cytokine secretion in maternal or cord blood, and found that leucocyte counts, maternal age, pre-conception BMI, smoking and season were associated with the levels of several CK in mothers or children.
DISCUSSION
Our study reveals immune imprinting influencing immune responses in infants, opening the way to investigate the mechanisms responsible for this imprinting. Whether such influences have long lasting effects on children health warrants further investigation.
Topics: Infant, Newborn; Infant; Humans; Female; Pregnancy; Interleukin-10; Interleukin-8; Interleukin-6; Prospective Studies; Cytokines; Immunity, Innate; Mother-Child Relations
PubMed: 37081891
DOI: 10.3389/fimmu.2023.1136749 -
BioFactors (Oxford, England) 2023Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory...
Crocetin regulates Th1/Th2 and Th17/Treg balances, nitric oxide production, and nuclear localization of NF-κB in Th2-provoked and normal situations in human-isolated lymphocytes.
Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory and anti-inflammatory properties may cause the biological activities of crocetin. Nevertheless, it is not still clear how this compound acts and causes an immune-modulatory impact on human lymphocytes. The effects of three concentrations (5, 10, and 20 μM) of crocetin or dexamethasone (0.1 mM) were assessed on gene expression and secretion of cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) level, and nitric oxide (NO) production in phytohaemagglutinin (PHA)-stimulated and non-stimulated lymphocytes. By incubation with PHA, gene expression and cytokine concentration comprising interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-4 were increased, along with NF-κB concentration and NO production (all, p < 0.001). In comparison with the controls, an alteration occurred in the T-helper (Th)2/Th1 and Th17/Treg balance in the stimulated lymphocyte toward a Th2 and Th17 response. In stimulated cells, crocetin and dexamethasone decreased pro-inflammatory significantly and increased anti-inflammatory cytokines and related gene expression, respectively. Moreover, Th17/Treg and Th1/Th2 balance was changed toward Treg and Th1 significantly reducing NF-κB and NO levels (p < 0.05 to p < 0.001). Promoting effects were represented by crocetin on T-cell subsets to Treg and Th1. Hence, it can have therapeutic value for treating predominant diseases of Th2 or Th17 cells.
Topics: Humans; NF-kappa B; Nitric Oxide; T-Lymphocytes, Regulatory; Th17 Cells; Cytokines; Anti-Inflammatory Agents; Dexamethasone
PubMed: 36747328
DOI: 10.1002/biof.1942 -
Molecular and Cellular Biochemistry Feb 2022Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an...
Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.
Topics: Humans; Inflammation; Monocytes; Phytohemagglutinins; Picrates; Signal Transduction; THP-1 Cells
PubMed: 34775567
DOI: 10.1007/s11010-021-04296-x