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Pharmacological Reports : PR Feb 2021Inflammation is characterized as a defensive response of our body against endogenous or exogenous stimuli. Chronic inflammation and oxidative stress play an important...
BACKGROUND
Inflammation is characterized as a defensive response of our body against endogenous or exogenous stimuli. Chronic inflammation and oxidative stress play an important role in the pathogenesis of various disorders such as asthma, cancers, and multiple sclerosis. Recently, diverse pharmacological activities of auraptene, a natural prenyloxycoumarin, were reported. In the present study, we aimed to evaluate the anti-oxidative and anti-inflammatory effects of auraptene on human isolated lymphocytes.
METHOD
The effects of auraptene (10, 30 and 90 μM) and dexamethasone (0.1 mM) were evaluated on cell viability, reactive oxygen species (ROS), and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione content (GSH) as well as the secretion of interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α in phytohemagglutinin (PHA)-stimulated human lymphocytes.
RESULTS
Auraptene (10-90 μM) did not affect lymphocytes' viability after 48 h incubation. PHA markedly elevated ROS, MDA, IL-6, and TNF-α levels, while diminished the GSH content, and CAT and SOD activities in human lymphocytes (p < 0.001 for all cases). Treatment with auraptene (10-90 µM) significantly ameliorated ROS, MDA, IL-6, and TNF-α levels, and markedly increased GSH content, and CAT and SOD activities (p < 0.5-0.001).
CONCLUSION
Auraptene may possess promising healing effects in the different inflammatory disorders associated with activation of the acquired immune system such as multiple sclerosis and asthma.
Topics: Adult; Antioxidants; Cell Survival; Coumarins; Cytokines; Dexamethasone; Humans; In Vitro Techniques; Inflammation; Male; Phytohemagglutinins; Reactive Oxygen Species; T-Lymphocytes; Young Adult
PubMed: 32166733
DOI: 10.1007/s43440-020-00083-5 -
Foods (Basel, Switzerland) Nov 2020Lectins or carbohydrate-binding proteins are widely distributed in seeds and vegetative parts of edible plant species. A few lectins from different fruits and vegetables... (Review)
Review
Lectins or carbohydrate-binding proteins are widely distributed in seeds and vegetative parts of edible plant species. A few lectins from different fruits and vegetables have been identified as potential food allergens, including wheat agglutinin, hevein (Hev b 6.02) from the rubber tree and chitinases containing a hevein domain from different fruits and vegetables. However, other well-known lectins from legumes have been demonstrated to behave as potential food allergens taking into account their ability to specifically bind IgE from allergic patients, trigger the degranulation of sensitized basophils, and to elicit interleukin secretion in sensitized people. These allergens include members from the different families of higher plant lectins, including legume lectins, type II ribosome-inactivating proteins (RIP-II), wheat germ agglutinin (WGA), jacalin-related lectins, GNA ( agglutinin)-like lectins, and Nictaba-related lectins. Most of these potentially active lectin allergens belong to the group of seed storage proteins (legume lectins), pathogenesis-related protein family PR-3 comprising hevein and class I, II, IV, V, VI, and VII chitinases containing a hevein domain, and type II ribosome-inactivating proteins containing a ricin B-chain domain (RIP-II). In the present review, we present an exhaustive survey of both the structural organization and structural features responsible for the allergenic potency of lectins, with special reference to lectins from dietary plant species/tissues consumed in Western countries.
PubMed: 33255208
DOI: 10.3390/foods9121724 -
Stem Cell Research & Therapy Apr 2024Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex...
BACKGROUND
Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem.
METHODS
In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay.
RESULTS
Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary.
CONCLUSIONS
The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.
Topics: Female; Animals; Mesenchymal Stem Cells; Mice; Ovary; Oocytes; Mesenchymal Stem Cell Transplantation; Ovarian Follicle
PubMed: 38650029
DOI: 10.1186/s13287-024-03718-z -
Clinical Immunology (Orlando, Fla.) May 2022Potential etiologies of TBNK SCID include both hematopoietic defects and thymic aplasia. The management of patients with this phenotype, identified by newborn screen,...
Potential etiologies of TBNK SCID include both hematopoietic defects and thymic aplasia. The management of patients with this phenotype, identified by newborn screen, may be unclear in the absence of a genetic diagnosis. We report an infant with lymphocyte flow cytometry consistent with TBNK SCID and reduced proliferative response to phytohemagglutinin. The patient had no genetic diagnosis after targeted panel and exome sequencing. The decision to trend laboratory values rather than move immediately to hematopoietic cell transplant was made given the absence of a genetic defect and the finding of a normal thymus on ultrasound. During the course of evaluation for transplant, the patient unexpectedly had normalization of T cell number and function. This case demonstrates a role for mediastinal ultrasound and the utility of trending laboratory values in patients with severe T cell lymphopenia but no genetic diagnosis, given the small but important possibility of spontaneous resolution.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Infant, Newborn; Lymphopenia; Neonatal Screening; Severe Combined Immunodeficiency; T-Lymphocytes
PubMed: 35447312
DOI: 10.1016/j.clim.2022.109014 -
The Journal of Asthma : Official... Sep 2022There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the...
BACKGROUND
There is a lack of information about regulatory T cells (Tregs) and inflammatory phenotypes in patients with asthma. In this study, we aimed to compare the characteristics of Tregs in patients with eosinophilic asthma.
METHODS
Forty healthy and 120 stable asthmatic patients were recruited. Sputum and airway inflammatory phenotypes were assessed, and all patients were followed for one year. Human peripheral blood mononuclear cells (PBMCs) were collected and stimulated with phytohemagglutinin (PHA) and Dermatophagoides farina (Derp) to detect CD4+CD25+FOXP3+T cells and levels. Interleukin (IL)-13, IL-5, IL-17, IL-9, and interferon (IFN)-γ levels were measured.
RESULTS
38.33% of patients had eosinophilic asthma, 13.33% had neutrophilic asthma, 6.67% had mixed granulocytic asthma, and 41.67% had pauci-granulocytic asthma. The eosinophilic asthma patients had a relatively high Asthma Control Test (ACT) score, an increased prediction and improvement FEV1 (%) rate, and elevated total IgE serum levels ( < 0.05). T helper cell 2 (Th2) cytokines IL-13 and IL-5 were predominantly expressed in the eosinophilic phenotype, while the Th1 cytokine IFN-γ and Th17 cytokine were found in the neutrophilic phenotype. IL-10 was significantly lower in eosinophilic asthmatic patients compared to the controls ( < 0.05). CD4+CD25+FOXP3+T cells (%Tregs) and gene expression in the PHA stimulated eosinophilic asthma samples were significantly lower compared to the control samples ( < 0.05). The airway inflammation phenotypes remained stable after one-year of therapy.
CONCLUSION
Asthmatic patients with the eosinophilic phenotype in this study were deficient in Tregs, as characterized by a Th2 cell-biased pattern.
Topics: Asthma; Cytokines; Forkhead Transcription Factors; Humans; Interleukin-5; Leukocytes, Mononuclear; Pulmonary Eosinophilia; T-Lymphocytes, Regulatory
PubMed: 34346277
DOI: 10.1080/02770903.2021.1962908 -
Tissue Engineering. Part A May 2021Mammalian platelets participate in the immediate tissue injury response by initiating coagulation and further promoting tissue injury mitigation and repair. The latter...
Mammalian platelets participate in the immediate tissue injury response by initiating coagulation and further promoting tissue injury mitigation and repair. The latter properties are deployed following platelet release of presynthetized morphogens, cytokines, and growth and chemotactic factors, which launch a tissue regenerative, angiogenic, and anti-inflammatory program. Several blood-derived biologic products, like platelet-rich plasma (PRP) and platelet lysate (PL), are currently on the market to allow proper healing and tissue regeneration. However, not all growth factors are released from the platelets and the final products contain plasma proteins such as albumin, fibrinogen, complement, and immunoglobulins, increasing the risks of serum sickness or allergic reaction. To address this problem, we developed a new platelet extract where equine blood platelets are concentrated, washed, and thereafter lysed by detergent Triton X-114. Distinct from PRP, this extract is devoid of albumin, fibrinogen, and immunoglobulins and is 266-fold enriched in platelet-derived growth factor content relative to PRP. Washed equine platelet extract (WEPLEX) is amenable to lyophilization without loss of biological activity. , WEPLEX significantly inhibits human and equine T cell proliferative response to phytohemagglutinin and also polarizes murine CD45/CD11b peritoneal macrophages to an IL-10 M2-like phenotype. , WEPLEX substantially improves clinical outcome of murine experimental dextran sulfate sodium colitis. We propose that equine-sourced, zoonosis-free WEPLEX may serve as an anti-inflammatory biological therapy across mammalian species.
Topics: Animals; Anti-Inflammatory Agents; Biological Products; Blood Platelets; Horses; Humans; Mice; Plant Extracts; Platelet-Rich Plasma
PubMed: 32854583
DOI: 10.1089/ten.TEA.2020.0160 -
Journal of Dairy Science Apr 2023We examined whether distinct staphylococcal and mammaliicoccal species and strains trigger B- and T-lymphocyte proliferation and interleukin (IL)-17A and interferon...
We examined whether distinct staphylococcal and mammaliicoccal species and strains trigger B- and T-lymphocyte proliferation and interleukin (IL)-17A and interferon (IFN)-γ production by peripheral blood mononuclear cells in nulliparous, primiparous, and multiparous dairy cows. Flow cytometry was used to measure lymphocyte proliferation with the Ki67 antibody, and specific monoclonal antibodies were used to identify CD3, CD4, and CD8 T lymphocyte and CD21 B lymphocyte populations. The supernatant of the peripheral blood mononuclear cell culture was used to measure IL-17A and IFN-γ production. Two distinct, inactivated strains of bovine-associated Staphylococcus aureus [one causing a persistent intramammary infection (IMI) and the other from the nose], 2 inactivated Staphylococcus chromogenes strains [one causing an IMI and the other from a teat apex), as well as an inactivated Mammaliicoccus fleurettii strain originating from sawdust from a dairy farm, and the mitogens concanavalin A and phytohemagglutinin M-form (both specifically to measure lymphocyte proliferation) were studied. In contrast to the "commensal" Staph. aureus strain originating from the nose, the Staph. aureus strain causing a persistent IMI triggered proliferation of CD4 and CD8 subpopulations of T lymphocytes. The M. fleurettii strain and the 2 Staph. chromogenes strains had no effect on T- or B-cell proliferation. Furthermore, both Staph. aureus and Staph. chromogenes strains causing persistent IMI significantly increased IL-17A and IFN-γ production by peripheral blood mononuclear cells. Overall, multiparous cows tended to have a higher B-lymphocyte and a lower T-lymphocyte proliferative response than primiparous and nulliparous cows. Peripheral blood mononuclear cells of multiparous cows also produced significantly more IL-17A and IFN-γ. In contrast to concanavalin A, phytohemagglutinin M-form selectively stimulated T-cell proliferation.
Topics: Female; Cattle; Animals; Phytohemagglutinins; Interleukin-17; Concanavalin A; Leukocytes, Mononuclear; Staphylococcus aureus; Staphylococcal Infections; Antibodies, Monoclonal; Cell Proliferation; Mastitis, Bovine; Milk; Cattle Diseases
PubMed: 36870844
DOI: 10.3168/jds.2022-22529 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250 -
Asia Pacific Allergy Dec 2023White bean allergy is uncommon and rarely reported. Herein, we report a case of white bean allergy in a patient with Down syndrome. A 7-year-old girl with Down syndrome...
White bean allergy is uncommon and rarely reported. Herein, we report a case of white bean allergy in a patient with Down syndrome. A 7-year-old girl with Down syndrome experienced allergic symptoms twice after eating white bean and visited our hospital for a food allergy investigation. An ImmunoCAP assay revealed a white bean-specific IgE (13.4 kU/L) in the patient's serum. In addition, her skin prick test result was positive. Moreover, ingestion of 2 g of boiled white beans in an oral food challenge test induced intermittent cough, desaturation, generalized urticaria, abnormal sleep, and mild hypotension. Thus, we diagnosed the patient with white bean allergy. We performed western blotting and mass spectrometric analysis and detected the following allergens: Phytohemagglutinin, group 3 late embryogenesis abundant protein, lipoxygenase, and legumin. In addition, we detected several candidate allergenic proteins for the first time. White bean, runner bean, or azuki bean was considered the primary source of sensitization because although immunoblotting inhibition tests revealed that the abovementioned beans inhibited other legumes, soybean, which she tolerates, showed little inhibition of the other legumes. However, we could not confirm whether the patient could ingest legumes other than soybean or white bean because her family did not wish to continue with further testing. This is the first report of a case of systemic allergic reactions to white bean in a child with Down syndrome. Further studies are needed to identify white bean allergens and understand the relationship between Down syndrome and white bean allergy.
PubMed: 38094097
DOI: 10.5415/apallergy.0000000000000111 -
International Journal of... 2021Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and...
INTRODUCTION
Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown.
METHODS
We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where "mitogens" means "polyclonal activators" (PA): phytohemagglutinin , phytohemagglutinin M, concanavalin A, and lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells.
RESULTS
The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower "stimulation index of polyclonal activators" (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype.
CONCLUSION
Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.
Topics: Cell Line; Cell Line, Tumor; Cytokines; Female; Humans; Triple Negative Breast Neoplasms
PubMed: 34399595
DOI: 10.1177/20587384211034089