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Plants (Basel, Switzerland) Jun 2024L. has been widely used by humans for centuries for various purposes, such as industrial, ceremonial, medicinal, and food. The bioactive components of L. can be...
L. has been widely used by humans for centuries for various purposes, such as industrial, ceremonial, medicinal, and food. The bioactive components of L. can be classified into two main groups: cannabinoids and terpenes. These bioactive components of L. leaf and inflorescence extracts were analyzed. Mice were systemically administered 30 mg/kg of L. leaf extract 1 h before lipopolysaccharide (LPS) administration, and behavioral tests were performed. We conducted an investigation into the oxygen saturation, oxygen tension, and degranulation of mast cells (MCs) in the deep cervical lymph nodes (DCLNs). To evaluate the anti-inflammatory effect of L. extracts in BV2 microglial cells, we assessed nitrite production and the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The main bioactive components of the L. extracts were THCA (a cannabinoid) and β-caryophyllene (a terpene). L. leaf extract reduced the immobility time in the forced swimming test and increased sucrose preference in the LPS model, without affecting the total distance and time in the center in the open field test. Additionally, L. leaf extract improved oxygen levels and inhibited the degranulation of MCs in DCLNs. The L. extracts inhibited IL-1β, IL-6, TNF-α, nitrite, iNOS, and COX-2 expression in BV2 microglia cells. The efficacy of L. extracts was suggested to be due to the entourage effect of various bioactive phytochemicals. Our findings indicate that these extracts have the potential to be used as effective treatments for a variety of diseases associated with acute inflammatory responses.
PubMed: 38931051
DOI: 10.3390/plants13121619 -
Life (Basel, Switzerland) May 2024Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North... (Review)
Review
Allergic conjunctivitis is an allergen-induced immune response secondary to the binding of immunoglobulin-E (IgE) to sensitized mast cells. Approximately 40% of North Americans and 20% of the world's population are impacted by some form of allergy and it continues to increase in prevalence, especially among children. Specified IgE antibodies can be found in almost all cases of exposure to seasonal or perennial allergens. Activation and degranulation of mast cells lead to increased tear levels of histamine, tryptase, leukotrienes, cytokines, and prostaglandins. The release of these factors initiates the recruitment of inflammatory cells in the conjunctival mucosa, which causes the late-phase reaction. Signs and symptoms of ocular allergies include itching, tearing, chemosis, and hyperemia, which can lead to decreased productivity and poor quality of life. Many treatment options are available to improve symptoms, including, mast cell stabilizers, antihistamines, dual-acting agents, steroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and other off-label treatment modalities. This review article provides an overview of different types of allergic conjunctivitis, its pathology and immunology, and recommended methods of treatment.
PubMed: 38929634
DOI: 10.3390/life14060650 -
International Journal of Molecular... Jun 2024Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to...
Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to infection. Neutrophils have been shown to be involved in the pathogenesis of sepsis by exacerbating inflammation. However, the exact effector mechanism of action still remains a mystery. Changes in the glycosylation pattern of the immunoglobulin G (IgG) Fc region are described for several diseases including meningococcal sepsis. In this study, we investigated the possible contribution of neutrophils and neutrophil implication, potentially related to degranulation or neutrophil extracellular trap (NET) formation in changing the IgG Fc N-glycosylation pattern in a murine sepsis model. We have measured the serum level of cytokines/chemokines and immunoglobulins, the serum activity of neutrophil elastase (NE), and analyzed the IgG Fc glycosylation pattern by Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) and Lectin enzyme-linked immunosorbent assay (ELISA). We observed an increased activity of NE- and neutrophil-associated cytokines such as keratinocyte chemoattractant (KC) with the development of sepsis. Regarding the IgG Fc N-glycosylation, we observed an increase in fucosylation and α1,3-galactosylation and a decrease for sialyation. Interestingly, these changes were not uniform for all IgG subclasses. After depletion of neutrophils, we saw a change in the exposure of fucose and α2,6-linked sialic acid during the time course of our experimental sepsis model. In conclusion, neutrophils can influence changes in the IgG glycosylation pattern in experimental sepsis.
Topics: Animals; Sepsis; Neutrophils; Glycosylation; Immunoglobulin G; Mice; Disease Models, Animal; Cytokines; Immunoglobulin Fc Fragments; Mice, Inbred C57BL; Leukocyte Elastase; Male; Extracellular Traps; Glycoproteins
PubMed: 38928183
DOI: 10.3390/ijms25126478 -
International Journal of Molecular... Jun 2024The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We...
BACKGROUND
The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We examined changes in leukocyte levels, eosinophil activity, and cytokine profiles in patients hospitalized with COVID-19.
METHODS
Serum samples were collected within the first 10 days of hospitalization/confirmed infection and analyzed for eosinophil granule proteins (EGP) and cytokines. Information from medical records including comorbidities, clinical symptoms, medications, and complete blood counts were collected at the time of admission, during hospitalization and at follow up approximately 3 months later.
RESULTS
Serum levels of eotaxin, type 1 and type 2 cytokines, and alarmin cytokines were elevated in COVID-19 patients, highlighting the heightened immune response ( < 0.05). However, COVID-19 patients exhibited lower levels of eosinophils and eosinophil degranulation products compared to hospitalized controls ( < 0.05). Leukocyte counts increased consistently from admission to follow-up, indicative of recovery.
CONCLUSION
Attenuated eosinophil activity alongside elevated chemokine and cytokine levels during active infection, highlights the complex interplay of immune mediators in the pathogenesis COVID-19 and underscores the need for further investigation into immune biomarkers and treatment strategies.
Topics: Humans; COVID-19; Male; Biomarkers; Female; Middle Aged; Eosinophils; Cytokines; Aged; SARS-CoV-2; Leukocyte Count; Adult; Hospitalization; Chemokine CCL11
PubMed: 38928133
DOI: 10.3390/ijms25126427 -
Journal of Leukocyte Biology Jun 2024Eosinophil-mediated pathophysiology is tissue destructive and tissue altering with proinflammatory, prothrombotic, and profibrotic effects. The distinctive morphology of...
Eosinophil-mediated pathophysiology is tissue destructive and tissue altering with proinflammatory, prothrombotic, and profibrotic effects. The distinctive morphology of an eosinophil reveals a cytoplasm chockfull of unique granules, and the granule proteins have numerous toxic effects on cells, tissues, and organs. Eosinophils are not found in most human tissues, and eosinophil involvement in diseased tissues generally is identified by cell infiltration on histopathologic examination. However, eosinophils characteristically lose their structural integrity and deposit granules and granule proteins at sites of inflammation. Hence, their participation in tissue damage may be underrecognized or entirely overlooked. The eosinophil major basic protein 1 is a toxic granule protein and, when deposited, persists in tissues. Major basic protein 1 deposition can be regarded as a footprint of eosinophil activity. Analyses of numerous eosinophil-related diseases have demonstrated clear-cut evidence of major basic protein 1 deposition in affected tissues where eosinophils were not recognized by hematoxylin and eosin tissue staining and light microscopy. Eosinophil granule protein deposition, as exemplified by localization of major basic protein 1, especially when disproportionately greater than cellular infiltration, emerges as a biomarker of hidden eosinophil-related pathophysiology. Consequently, current assessments of recognized eosinophils may vastly underestimate their role in disease.
PubMed: 38922831
DOI: 10.1093/jleuko/qiae052 -
Stem Cell Reviews and Reports Jun 2024Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This...
Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This study investigated changes in the secretome of perirenal ASC (prASC) under different conditions: normoxia, cytokine exposure, high glucose, hypoxia, and hypoxia with high glucose. Using mass spectrometry and enrichment clustering analysis, we found that normoxia enriched pathways related to extracellular matrix (ECM) organization, platelet degranulation, and insulin-like growth factor (IGF) transport and uptake. Cytokine exposure influenced metabolism, vascular development, and protein processing pathways. High glucose affected the immune system, metabolic processes, and IGF transport and uptake. Hypoxia impacted immune and metabolic processes and protein processing. Combined hypoxia and high glucose influenced the immune system, IGF transport and uptake, and ECM organization. Our findings highlight the potential of manipulating culturing conditions to produce secretomes with distinct protein and functional profiles, tailoring therapeutic strategies accordingly.
PubMed: 38922529
DOI: 10.1007/s12015-024-10748-w -
Pathogens (Basel, Switzerland) May 2024Disseminated leishmaniasis (DL) caused by is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against is mediated by...
Disseminated leishmaniasis (DL) caused by is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against is mediated by macrophages upon activation by IFN-γ produced by CD4T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8T cells. Herein, we evaluate the participation of senescent CD8T cells in the pathogenesis of DL. Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8T cells. Statistical analysis was performed using the Mann-Whitney and Kruskal-Wallis tests, followed by Dunn's. Patients with DL have an increase in the frequency of circulating CD8T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients' circulating CD8T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. DL patients show a higher frequency of cytotoxic senescent CD8T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing to the extracellular compartment, contributing to the spread of parasites.
PubMed: 38921758
DOI: 10.3390/pathogens13060460 -
Advances in Respiratory Medicine May 2024Ragweed pollen allergy is the most common seasonal allergy in western Romania. Prolonged exposure to ragweed pollen may induce sensitization to pan-allergens such as...
Ragweed pollen allergy is the most common seasonal allergy in western Romania. Prolonged exposure to ragweed pollen may induce sensitization to pan-allergens such as calcium-binding proteins (polcalcins) and progression to more severe symptoms. We aimed to detect IgE sensitization to recombinant Amb a 9 and Amb a 10 in a Romanian population, to assess their potential clinical relevance and cross-reactivity, as well as to investigate the relation with clinical symptoms. rAmb a 9 and rAmb a 10 produced in were used to detect specific IgE in sera from 87 clinically characterized ragweed-allergic patients in ELISA, for basophil activation experiments and rabbit immunization. Rabbit rAmb a 9- and rAmb a 10-specific sera were used to detect possible cross-reactivity with rArt v 5 and reactivity towards ragweed and mugwort pollen extracts. The results showed an IgE reactivity of 25% to rAmb a 9 and 35% to rAmb a 10. rAmb a 10 induced basophil degranulation in three out of four patients tested. Moreover, polcalcin-negative patients reported significantly more skin symptoms, whereas polcalcin-positive patients tended to report more respiratory symptoms. Furthermore, both rabbit antisera showed low reactivity towards extracts and showed high reactivity to rArt v 5, suggesting strong cross-reactivity. Our study indicated that recombinant ragweed polcalcins might be considered for molecular diagnosis.
Topics: Humans; Immunoglobulin E; Cross Reactions; Rhinitis, Allergic, Seasonal; Romania; Calcium-Binding Proteins; Antigens, Plant; Allergens; Female; Male; Ambrosia; Rabbits; Adult; Plant Extracts
PubMed: 38921061
DOI: 10.3390/arm92030022 -
Nature Biotechnology Jun 2024Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased...
Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased functional mapping of tumor-infiltrating NK (TINK) cells using in vivo adeno-associated virus (AAV)-SB (Sleeping Beauty)-CRISPR (clustered regularly interspaced short palindromic repeats) screens in four solid tumor mouse models. In parallel, we characterized single-cell transcriptomic landscapes of TINK cells, which identified previously unexplored subpopulations of NK cells and differentially expressed TINK genes. As a convergent hit, CALHM2-knockout (KO) NK cells showed enhanced cytotoxicity and tumor infiltration in mouse primary NK cells and human chimeric antigen receptor (CAR)-NK cells. CALHM2 mRNA reversed the CALHM2-KO phenotype. CALHM2 KO in human primary NK cells enhanced their cytotoxicity, degranulation and cytokine production. Transcriptomics profiling revealed CALHM2-KO-altered genes and pathways in both baseline and stimulated conditions. In a solid tumor model resistant to unmodified CAR-NK cells, CALHM2-KO CAR-NK cells showed potent in vivo antitumor efficacy. These data identify endogenous genetic checkpoints that naturally limit NK cell function and demonstrate the use of CALHM2 KO for engineering enhanced NK cell-based immunotherapies.
PubMed: 38918616
DOI: 10.1038/s41587-024-02282-4 -
The Journal of Clinical Investigation Jun 2024Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to...
Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, non-destructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here we report a completely different mechanism by which neutrophils act non-destructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy subjects. This non-destructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.
PubMed: 38916955
DOI: 10.1172/JCI171691