keyword
https://read.qxmd.com/read/38489062/safety-of-biological-therapies-for-severe-asthma-an-analysis-of-suspected-adverse-reactions-reported-in-the-who-pharmacovigilance-database
#1
JOURNAL ARTICLE
Paola Maria Cutroneo, Elena Arzenton, Fabiana Furci, Fabio Scapini, Maria Bulzomì, Nicoletta Luxi, Marco Caminati, Gianenrico Senna, Ugo Moretti, Gianluca Trifirò
BACKGROUND: The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs...
March 15, 2024: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://read.qxmd.com/read/38479672/achyranthes-bidentata-polysaccharides-improve-cyclophosphamide-induced-adverse-reactions-by-regulating-the-balance-of-cytokines-in-helper-t-cells
#2
JOURNAL ARTICLE
Yuan-Yuan Lei, Yu-Han Ye, Ying Liu, Jia-Ling Xu, Cheng-Lin Zhang, Chun-Ming Lyu, Chen-Guo Feng, Yan Jiang, Yang Yang, Yan Ke
The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased...
March 11, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38477552/rna-sequencing-of-paired-tape-strips-and-skin-biopsies-in-atopic-dermatitis-reveals-key-differences
#3
JOURNAL ARTICLE
Blaine Fritz, Anne-Sofie Halling, Isabel Díaz-Pinés Cort, Maria Oberländer Christensen, Amalie Thorsti Møller Rønnstad, Caroline Meyer Olesen, Mette Hjorslev Knudgaard, Claus Zachariae, Steffen Heegaard, Jacob P Thyssen, Thomas Bjarnsholt
BACKGROUND: Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. METHODS: Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5)...
March 13, 2024: Allergy
https://read.qxmd.com/read/38464040/a-tension-offloading-patch-mitigates-dermal-fibrosis-induced-by-pro-fibrotic-skin-injections
#4
Derrick Wan, Heather Talbott, Michelle Griffin, Shamik Mascharak, Jennifer Parker, Maxwell Kuhnert, Jason Guo, Nestor Diaz Deleon, Christopher Lavin, Darren Abbas, Nicholas Guardino, Annah Morgan, Caleb Valencia, Asha Cotterell, Michael Longaker
Skin fibrosis is a clinical problem with devastating impacts but limited treatment options. In the setting of diabetes, insulin administration often causes local dermal fibrosis, leading to a range of clinical sequelae including impeded insulin absorption. Mechanical forces are important drivers of fibrosis and, clinically, physical tension offloading at the skin level using an elastomeric patch significantly reduces wound scarring. However, it is not known whether tension offloading could similarly prevent skin fibrosis in the setting of pro-fibrotic injections...
March 1, 2024: Research Square
https://read.qxmd.com/read/38460411/saccharomyces-cerevisiae-cells-that-display-norovirus-p-induce-both-systemic-and-mucosal-neutralizing-antibodies
#5
JOURNAL ARTICLE
Xin He, Nianzhu Jiang, Yaoming Li
The human norovirus (HuNov) is the leading cause of acute gastroenteritis (AGE) worldwide. Mucosal secretory IgA (sIgA) in the gastrointestinal tract interrupts the interaction between host cells and HuNov, thus inhibiting viral infection. In this study, we constructed a recombinant Saccharomyces cerevisiae (S. cerevisiae) expressing the HuNov P protein (GII. 4) and evaluated its immunogenicity in mice after oral delivery. First, the recombinant S. cerevisiae (EBY100/pYD1-P) efficiently expressed P, as evidenced by western blotting and indirect fluorescent assay...
March 6, 2024: Virology
https://read.qxmd.com/read/38454025/high-inflammatory-cytokines-gene-expression-can-be-detected-in-workers-with-prolonged-exposure-to-silver-and-silica-nanoparticles-in-industries
#6
JOURNAL ARTICLE
Vahid Babaei, Azadeh Ashtarinezhad, Maryam Torshabi, Shahram Teimourian, Morteza Shahmirzaie, Jamileh Abolghasemi, Hamidreza Zeraatgar Gohardani, Eisa Kaveh Vernousfaderani, Farshad H Shirazi
Occupational health must be strictly considered in industries particularly in nanoparticle factories where workers were exposed to different types of chemicals. We measured the serum levels of inflammatory cytokines in workers who developed skin lesions after exposure to silver and silica nanoparticles. Using a questionnaire in this cross-sectional study, we identified 110 workers in nanoparticle industries who were exposed to silver and silica nanoparticles. We also included 40 healthy subjects as controls from the administrative department of the same factories who were not exposed to nanoparticles...
March 7, 2024: Scientific Reports
https://read.qxmd.com/read/38450676/chemical-chaperone-tudca-selectively-inhibits-production-of-allergen-specific-ige-in-a-low-dose-model-of-allergy
#7
JOURNAL ARTICLE
D B Chudakov, O A Shustova, O D Kotsareva, A A Generalov, M S Streltsova, Yu D Vavilova, G V Fattakhova
The cellular response to endoplasmic reticulum (ER) stress accompanies plasma cell maturation and is one of triggers and cofactors of the local inflammatory response. Chemical chaperones, low-molecular substances that eliminate pathological ER stress, are proposed as means of treating pathologies associated with ER stress. The aim of this study was to evaluate the effect and mechanisms of influence of chemical chaperones on the humoral response in a low-dose model of allergy. The allergic immune response was induced in BALB/c mice by repeated administration of ovalbumin at a dose of 100 ng for 6 weeks...
February 2024: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://read.qxmd.com/read/38442583/bergapten-inhibits-airway-inflammation-and-mrgprx2-mediated-mast-cells-activation-by-targeting-nr4a1
#8
JOURNAL ARTICLE
Jue Wang, Yuanyuan Wu, Xiao Li, Xinghui Wang, Shuanying Yang
Asthma is a serious global health problem affecting 300 million persons around the world. Mast cells (MCs) play a major role in airway hyperresponsiveness (AHR) and inflammation in asthma, their exact effector mechanisms remain unclear. Here, we aim to investigate the inhibitory effect of Bergapten (BER) on MRGPRX2-mediated MCs activation through asthma model. Mouse model of asthma was established to examine the anti-asthmatic effects of BER. Calcium (Ca2+ ) influx, β-hexosaminidase and histamine release were used to assess MCs degranulation in vitro...
March 4, 2024: International Immunopharmacology
https://read.qxmd.com/read/38433560/role-of-qufeng-tongqiao-prescription-in-the-protection-of-cerebral-ischemia-and-associated-molecular-network-mechanism
#9
JOURNAL ARTICLE
Xue Bai, Shen Wang, Na Li, Min Xu, Ji-Lin Chen, Yan-Ping Qian, Ting-Hua Wang
To explore the of Qufeng Tongqiao Prescription in the treatment of cerebral ischemia-reperfusion (CIR) and associated molecular network mechanism. Venny diagram, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis, protein-protein interaction (PPI), hub genes mining, molecular docking, combined with animal experiments and Nissl stain were performed to determine the molecular network mechanism of Qufeng Tongqiao Prescription for CIR treatment. Fifty three intersecting genes between Qufeng Tongqiao Prescription and cerebral ischemia reperfusion were acquired from Venny analysis...
March 2024: Chemical Biology & Drug Design
https://read.qxmd.com/read/38427690/hyperglycaemia-amplifies-tlr-mediated-inflammatory-response-of-m-il4-macrophages-to-dyslipidemic-ligands
#10
JOURNAL ARTICLE
Luis Ernesto Badillo-Garcia, Quan Liu, Kim Ziebner, Michael Balduff, Tatyana Sevastyanova, Christina Schmuttermaier, Harald Klüter, Martin Harmsen, Julia Kzhyshkowska
Hyperglycaemia is critical for initiation of diabetic vascular complications. We systemically addressed the role of hyperglycaemia in the regulation of TLRs in primary human macrophages. Expression of TLRs (1-9) was examined in monocyte-derived M(NC), M(IFNγ) and M(IL4) differentiated in normoglycemic and hyperglycaemic conditions. Hyperglycaemia increased expression of TLR1 and TLR8 in M(NC), TLR 2 and 6 in M(IFNγ), and TLR4 and TLR5 in M(IL4). The strongest effect of hyperglycaemia in M(IL4) was the upregulation of TLR4 gene and protein expression...
March 1, 2024: Journal of Leukocyte Biology
https://read.qxmd.com/read/38426866/global-il4r%C3%AE-blockade-exacerbates-heart-failure-after-an-ischemic-event-in-mice-and-humans
#11
JOURNAL ARTICLE
Santiago Alvarez-Argote, Victor Alencar Almedia, Makenna C Knas, Sydney L Buday, Michaela Patterson, Caitlin C O'Meara
Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding mechanisms preventing or exacerbating disease progression. Literature suggests an important role for activation of interleukin 13 or interleukin 4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans...
March 1, 2024: American Journal of Physiology. Heart and Circulatory Physiology
https://read.qxmd.com/read/38423493/the-cytokine-genes-of-oncorhynchus-masou-formosanus-include-a-defective-interleukin-4-13a-gene
#12
JOURNAL ARTICLE
Ying-Hsuan Yen, De Yu Zheng, Shu Yuan Yang, Jin-Chywan Gwo, Sebastian D Fugmann
Oncorhynchus masou formosanus (Formosa landlocked salmon) is a critically endangered salmonid fish endemic to Taiwan. To begin to understand how its drastic change in lifestyle from anadromous to exclusively river-dwelling is reflected in its immune genes, we characterized the genes encoding six cytokines (IL-2A, IL-2B, IL-4/13A, IL-4/13B1, IL-4/13B2, and IL-17A/F2a) important for T cell responses as no genomic data is available for this fish. Interestingly, all genes appeared homozygous indicative of a genetic bottleneck...
February 27, 2024: Developmental and Comparative Immunology
https://read.qxmd.com/read/38412117/magnesium-supplementation-modulates-t-cell-function-in-people-with-type-2-diabetes-and-low-serum-magnesium-levels
#13
JOURNAL ARTICLE
Linda C A Drenthen, Mandala Ajie, Jeroen H F de Baaij, Cees J Tack, Bastiaan E de Galan, Rinke Stienstra
CONTEXT: Low magnesium levels, which are common in people with type 2 diabetes, are associated with increased levels of pro-inflammatory molecules. It is unknown whether magnesium supplementation decreases this low-grade inflammation in people with type 2 diabetes. OBJECTIVE: We performed a multidimensional immunophenotyping to better understand the effect of magnesium supplementation on the immune system of people with type 2 diabetes and low magnesium levels. METHODS: Using a randomized, double-blind, placebo-controlled, two-period, cross-over study, we compared the effect of magnesium supplementation (15 mmol/day) to placebo on the immunophenotype including whole blood immune cell counts, T-cell and CD14+ monocyte function after ex vivo stimulation, and the circulating inflammatory proteome...
February 27, 2024: Journal of Clinical Endocrinology and Metabolism
https://read.qxmd.com/read/38405750/mechanisms-of-epigenomic-and-functional-convergence-between-glucocorticoid-and-il4-driven-macrophage-programming
#14
Dinesh K Deochand, Marija Dacic, Michael J Bale, Andrew W Daman, Steven Z Josefowicz, David Oliver, Yurii Chinenov, Inez Rogatsky
Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 promoting a tissue-repair homeostatic state (M2IL4). Glucocorticoids, widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2GC), but how such disparate pathways may functionally converge is unknown. We show using integrative functional genomics that M2IL4 and M2GC transcriptomes share a striking overlap mirrored by a shift in chromatin landscape in both common and signal-specific gene subsets...
February 18, 2024: bioRxiv
https://read.qxmd.com/read/38400692/upregulation-of-il4-induced-gene-1-enzyme-by-b2-cells-during-melanoma-progression-impairs-their-antitumor-properties
#15
JOURNAL ARTICLE
Fériel Bekkat, Malvina Seradj, Renée Lengagne, Frédéric Fiore, Masashi Kato, Bruno Lucas, Flavia Castellano, Valérie Molinier-Frenkel, Yolande Richard, Armelle Prévost-Blondel
B cells present in human cutaneous melanoma have been associated with protective or detrimental effects on disease progression according to their phenotype. By using the RET model of spontaneous melanoma and adoptive transfer of B16 melanoma cells, we show that immature and follicular B2 (B2-FO) cells exert a protective effect on melanoma progression by promoting the generation of effector memory T cells and limiting the recruitment of polymorphonuclear myeloid-derived suppressor cells. Unfortunately, this beneficial effect progressively wanes as a consequence of enhanced expression of the IL4-induced gene 1 (IL4I1) enzyme by immature B cells and B2-FO cells...
February 24, 2024: European Journal of Immunology
https://read.qxmd.com/read/38376135/il-6-levels-dominate-the-serum-cytokine-signature-of-severe-epidermolysis-bullosa-a-prospective-cohort-study
#16
JOURNAL ARTICLE
A Reimer-Taschenbrecker, M Hess, M Davidovic, A Hwang, S Hübner, M Hofsaess, S Gewert, K Eyerich, C Has
BACKGROUND: Systemic inflammation is considered a major player in the pathogenesis of epidermolysis bullosa (EB), but its pattern has only been described in small heterogeneous cohorts. There is controversy if and how systemic inflammation should be therapeutically targeted. METHODS: We examined serum proinflammatory, anti-inflammatory, and itch related cytokines in a paediatric cohort of 29 patients with junctional and dystrophic EB. The cytokine that emerged as the most relevant was measured in a validation cohort of 42 patients during follow-up visits over 2 years...
February 20, 2024: Journal of the European Academy of Dermatology and Venereology: JEADV
https://read.qxmd.com/read/38371956/gb12-09-a-bispecific-antibody-targeting-il4r%C3%AE-and-il31r%C3%AE-for-atopic-dermatitis-therapy
#17
JOURNAL ARTICLE
Feiyan Deng, Yuxin Qiu, Xiangling Zhang, Nining Guo, Junhong Hu, Wenjie Yang, Wei Shang, Bicheng Liu, Suofu Qin
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by dysregulated immune responses. The key mediators of AD pathogenesis are T helper 2 (TH2) cells and TH2 cytokines. Targeting interleukin 4 (IL4), IL13 or IL31 has become a pivotal focus in both research and clinical treatments for AD. However, the need remains pressing for the development of a more effective and safer therapy, as the current approaches often yield low response rates and adverse effects. In response to this challenge, we have engineered a immunoglobulin G-single-chain fragment variable (scFv) format bispecific antibody (Ab) designed to concurrently target IL4R and IL31R...
January 2024: Antibody Therapeutics
https://read.qxmd.com/read/38360807/immune-endotyping-and-gene-expression-profile-of-patients-with-chronic-rhinosinusitis-with-nasal-polyps-in-the-aspirin-exacerbated-respiratory-disease-aerd-and-the-non-aerd-subgroups
#18
JOURNAL ARTICLE
Javad Nazari, Faezeh Shahba, Negin Jafariaghdam, Saleh Mohebbi, Saba Arshi, Mohammad Hassan Bemanian, Morteza Fallahpour, Sima Shokri, Fatemeh Atashrazm, Saeed Amini, Maryam Roomiani, Mahnaz Jamee, Pegah Babaheidarian, Majid Khoshmirsafa, Mohammad Nabavi
BACKGROUND: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP...
February 15, 2024: Allergy, Asthma, and Clinical Immunology
https://read.qxmd.com/read/38354656/il-4-induced-m2-macrophages-inhibit-fibrosis-of-endometrial-stromal-cells
#19
JOURNAL ARTICLE
Dan Feng, Yang Li, Hongyun Zheng, Ying Wang, Juexiao Deng, Tingting Liu, Wenxin Liao, Fujin Shen
BACKGROUND: Intrauterine adhesions (IUA) refers to endometrial fibrosis caused by irreversible damage of the endometrial basal layer. As the key regulators in tissue repair, regeneration, and fibrosis, macrophages play an essential role in endometrial regeneration and repair during the normal menstrual cycle. However, the mechanism of macrophages involved in IUA remains unclear. METHODS: In the late stages of proliferation, the endometrium was collected to make paraffin sections...
February 13, 2024: Reproductive Biology
https://read.qxmd.com/read/38350816/topical-application-of-activator-protein-1-inhibitor-t-5224-suppresses-inflammation-and-improves-skin-barrier-function-in-a-murine-atopic-dermatitis-like-dermatitis
#20
JOURNAL ARTICLE
Minori Sasakura, Hitoshi Urakami, Kota Tachibana, Kenta Ikeda, Ken-Ichi Hasui, Yoshihiro Matsuda, Ko Sunagawa, Daisuke Ennishi, Shuta Tomida, Shin Morizane
BACKGROUND: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders. METHODS: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice...
February 12, 2024: Allergology International: Official Journal of the Japanese Society of Allergology
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