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Frontiers in Veterinary Science 2024BP26 proves to be a highly immunogenic antigen with excellent specificity in brucellosis detection. In China, the authorized use of the Bp26-deleted vaccine M5ΔBP26...
BP26 proves to be a highly immunogenic antigen with excellent specificity in brucellosis detection. In China, the authorized use of the Bp26-deleted vaccine M5ΔBP26 for preventing small ruminant brucellosis highlights the importance of developing accurate detection methods targeting BP26, particularly for the diagnosis of differentiation between infected and vaccinated animals (DIVA). Using the traditional mouse hybridoma technique, we successfully obtained 12 monoclonal antibodies (mAbs) targeting BP26. The efficacy of these mAbs in detecting various animal brucellosis cases using the competitive ELISA method was evaluated. Among them, only the E10 mAb exhibited significant efficiency, being inhibited by 100, 97.62, and 100% of brucellosis-positive sera from cattle, small ruminants, and canines, respectively. The E10-based competitive enzyme-linked immunosorbent assay (cELISA) outperformed the BP26-based indirect enzyme-linked immunosorbent assay (iELISA) in accuracy, particularly for cattle and small ruminant brucellosis, with cELISA sensitivity reaching 97.62% compared to 64.29% for iELISA for small ruminants. Although cELISA showed slightly lower specificity than iELISA, it still maintained high accuracy in canine brucellosis detection. The epitope of mAb E10 was identified in the amino acid sequence QPIYVYPDDKNNLKEPTITGY, suggesting its potential as a diagnostic antigen for brucellosis. In conclusion, the E10-based cELISA presents an effective means of detecting animal brucellosis, particularly significant for DIVA diagnosis in China, where the BP26-mutant vaccine is widely used.
PubMed: 38957801
DOI: 10.3389/fvets.2024.1389728 -
Toxicology Research Aug 2024Allergic rhinitis (AR) a common and complicated upper airway disease mediated by specific IgE antibodies. Our study aims to explore the pharmacological effects of...
BACKGROUND
Allergic rhinitis (AR) a common and complicated upper airway disease mediated by specific IgE antibodies. Our study aims to explore the pharmacological effects of astragalus polysaccharide (APS) on AR and elucidate the mechanisms involved.
METHODS
RT-qPCR and Western blotting were used to analyze mRNA and protein expression. Interleukin (IL)-13-treated human nasal epithelial cells (hNECs) was employed as the AR cell model. Cell apoptosis and viability were evaluated by TUNEL staining and MTT assay, respectively. ROS level was examined by the DCFH-DA probe. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels were measured by the corresponding kits. FBXW7 mA modification level was assessed by MeRIP assay.
METHODS
Our results showed that APS treatment reduced cell apoptosis, ROS, and MDA levels while increasing SOD, CAT, and GSH-Px levels in IL-13-treated hNECs by activating the Nrf2/HO-1 pathway. Moreover, APS alleviated IL-13-induced oxidative stress injury in hNECs by downregulating WTAP. In addition, WTAP knockdown increased FBXW7 mRNA stability by regulating FBXW7 mRNA mA modification. It also turned out that APS alleviated IL-13-induced oxidative stress injury in hNECs through the WTAP/FBXW7 axis.
CONCLUSIONS
Taken together, APS inhibited WTAP-mediated FBXW7 mA modification to alleviate IL-13-induced oxidative stress injury in hNECs.
PubMed: 38957784
DOI: 10.1093/toxres/tfae099 -
Veterinary and Animal Science Sep 2024Q fever is a zoonosis whose main reservoirs are domestic ruminants. Surveillance in these species is carried out mainly with serological tests, which, however, have...
Q fever is a zoonosis whose main reservoirs are domestic ruminants. Surveillance in these species is carried out mainly with serological tests, which, however, have limited diagnostic performance, and their manufacturing requires laboratories equipped with high biosafety requirements for antigen production. Recombinant ELISAs do not depend on these requirements and, being based on a single antigen, can reduce potential false positivity by identifying antibodies specific to a phase of infection. The aim of this study was to apply a new technology (dual antigen test) to a recombinant protein (Ybgf), an antigen produced in recombinant form and already used in previous studies for the design of an indirect ELISA. The successfully produced recombinant antigen was used to coat 96-well plates and, at the same time, another antigen aliquot was conjugated with HRP to obtain an HRP-conjugated Ybgf. After setting the test conditions, the results obtained with the recombinant double antigen test were compared with those obtained with a commercial assay (considered as reference assay) testing a total of 514 ruminant samples (280 goats and 234 cattle). A concordance of 86.2 and a Cohen's Kappa value of 0.72 were obtained, with no significant difference between the two species tested. Notably, the test proved to be highly specific, having correctly identified 250 out of 253 animals. This research represents an additional effort to use recombinant antigens to enhance serological methods in veterinary medicine. In a "one-health scenario", improving the performance of serological tests used in veterinary practice also means improving the surveillance of this infection.
PubMed: 38957741
DOI: 10.1016/j.vas.2024.100366 -
Dermatology Reports Jun 2024The generalized and sclerodermic form of lichen myxedematosus, known as scleromyxedema (SMX), is a chronic mucinosis that manifests cutaneously and has multiple systemic...
The generalized and sclerodermic form of lichen myxedematosus, known as scleromyxedema (SMX), is a chronic mucinosis that manifests cutaneously and has multiple systemic comorbidities. There are few available treatment options and no established therapeutic guidelines. We describe a 48-year-old man who had intravenous immunoglobulins (IVIg), oral corticosteroids, and methotrexate (MTX) for the treatment of SMX, monoclonal gammopathy, and arthritis. Because of its effectiveness and high level of tolerance, IVIg is the most often used first-line therapy for SMX and has been used for an increasing range of skin conditions. In our instance, better control of skin disease and extracutaneous manifestations was made possible by combining IVIg with oral prednisone and MTX. To the best of our knowledge, this is the first instance of SMX treatment that has combined therapeutic approaches with a favorable safety profile.
PubMed: 38957635
DOI: 10.4081/dr.2023.9803 -
Oxidative Medicine and Cellular... 2024Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and...
Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals ( = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT . ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.
Topics: Animals; Rats; Myocardial Infarction; Disease Models, Animal; Male; Inflammation; Abatacept; Rats, Wistar; Myocardial Reperfusion Injury
PubMed: 38957586
DOI: 10.1155/2024/3534104 -
Frontiers in Immunology 2024Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune...
BACKGROUND
Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival.
MATERIALS AND METHODS
A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs.
RESULTS
A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01).
CONCLUSION
Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.
Topics: Humans; Immune Checkpoint Inhibitors; Male; Female; Carcinoma, Non-Small-Cell Lung; Aged; Retrospective Studies; Lung Neoplasms; Middle Aged; Bone Neoplasms; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Adult; Treatment Outcome
PubMed: 38957472
DOI: 10.3389/fimmu.2024.1379056 -
Frontiers in Immunology 2024Probiotic consumption strongly influences local intestinal immunity and systemic immune status. strain SANK70258 (HC) is a spore-forming lactic acid bacterium that has... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
strain SANK70258 suppresses symptoms of upper respiratory tract infection via immune modulation: a randomized, double-blind, placebo-controlled, parallel-group, comparative study.
Probiotic consumption strongly influences local intestinal immunity and systemic immune status. strain SANK70258 (HC) is a spore-forming lactic acid bacterium that has immunostimulatory properties on peripheral tissues. However, few reports have examined the detailed effectiveness of HC on human immune function and its mechanism of action. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to comprehensively evaluate the effects of HC on immunostimulatory capacity, upper respiratory tract infection (URTI) symptoms, and changes in intestinal organic-acid composition. Results of a questionnaire survey of URTI symptoms showed that runny nose, nasal congestion, sneezing, and sore throat scores as well as the cumulative number of days of these symptoms were significantly lower in the HC group than in the placebo group during the study period. Furthermore, the salivary secretory immunoglobulin A (sIgA) concentration was significantly higher, and the natural killer (NK) cell activity tended to be higher in the HC group than in the placebo group. In addition, we performed an exposure culture assay of inactivated influenza virus on peripheral blood mononuclear cells (PBMCs) isolated from the blood of participants in the HC and placebo groups. Gene-expression analysis in PBMCs after culture completion showed that IFNα and TLR7 expression levels were significantly higher in the HC group than in the placebo group. In addition, the expression levels of CD304 tended to be higher in the HC group than in the placebo group. On the other hand, the HC group showed a significantly higher increase in the intestinal butyrate concentration than the placebo group. HC intake also significantly suppressed levels of IL-6 and TNFα produced by PBMCs after exposure to inactivated influenza virus. Collectively, these results suggest that HC activated plasmacytoid dendritic cells expressing TLR7 and CD304 and strongly induced IFNα production, subsequently activating NK cells and increasing sIgA levels, and induced anti-inflammatory effects via increased intestinal butyrate levels. These changes may contribute to the acquisition of host resistance to viral infection and URTI prevention.
Topics: Humans; Respiratory Tract Infections; Double-Blind Method; Male; Adult; Probiotics; Female; Young Adult; Leukocytes, Mononuclear; Killer Cells, Natural; Gastrointestinal Microbiome; Immunoglobulin A, Secretory; Toll-Like Receptor 7; Immunomodulation
PubMed: 38957464
DOI: 10.3389/fimmu.2024.1389920 -
Frontiers in Neuroanatomy 2024Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of...
INTRODUCTION
Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of singly-innervated fibers (SIF). Recently, it has been established by our research group that these motoneuron types of monkey abducens and trochlear nuclei express distinct ion channel profiles: SIF motoneurons, as well as abducens internuclear neurons (INT), express strong Kv1.1 and Kv3.1b immunoreactivity, indicating their fast-firing capacity, whereas MIF motoneurons do not. Moreover, low voltage activated cation channels, such as Cav3.1 and HCN1 showed differences between MIF and SIF motoneurons, indicating distinct post-inhibitory rebound characteristics. However, the ion channel profiles of MIF and SIF motoneurons have not been established in human brainstem tissue.
METHODS
Therefore, we used immunohistochemical methods with antibodies against Kv, Cav3 and HCN channels to (1) examine the human trochlear nucleus in terms of anatomical organization of MIF and SIF motoneurons, (2) examine immunolabeling patterns of ion channel proteins in the distinct motoneurons populations in the trochlear and abducens nuclei.
RESULTS
In the examination of the trochlear nucleus, a third motoneuron subgroup was consistently encountered with weak perineuronal nets (PN). The neurons of this subgroup had -on average- larger diameters than MIF motoneurons, and smaller diameters than SIF motoneurons, and PN expression strength correlated with neuronal size. Immunolabeling of various ion channels revealed that, in general, human MIF and SIF motoneurons did not differ consistently, as opposed to the findings in monkey trochlear and abducens nuclei. Kv1.1, Kv3.1b and HCN channels were found on both MIF and SIF motoneurons and the immunolabeling density varied for multiple ion channels. On the other hand, significant differences between SIF motoneurons and INTs were found in terms of HCN1 immunoreactivity.
DISCUSSION
These results indicated that motoneurons may be more variable in human in terms of histochemical and biophysiological characteristics, than previously thought. This study therefore establishes grounds for any histochemical examination of motor nuclei controlling extraocular muscles in eye movement related pathologies in the human brainstem.
PubMed: 38957435
DOI: 10.3389/fnana.2024.1411154 -
Frontiers in Pharmacology 2024Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis. However, the effectiveness of anti-PD-1/PD-L1 treatment is limited when HCC becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in the negative regulation of PD-1 antibody targeted therapy in the tumor microenvironment (TME). Therefore, as an emerging direction in cancer immunotherapy research for the treatment of HCC, it is crucial to elucidate the correlations and mechanisms between TAMs and PD-1/PD-L1-mediated immune tolerance. This paper summarizes the effects of TAMs on the pathogenesis and progression of HCC and their impact on HCC anti-PD-1/PD-L1 immunotherapy, and further explores current potential therapeutic strategies that target TAMs in HCC, including eliminating TAMs in the TME, inhibiting TAMs recruitment to tumors and functionally repolarizing M2-TAMs (tumor-supportive) to M1-TAMs (antitumor type).
PubMed: 38957393
DOI: 10.3389/fphar.2024.1382256 -
Journal of Rheumatic Diseases Jul 2024Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female...
Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female Korean patient with early-onset interstitial lung disease who was initially suspected to have systemic lupus erythematosus (SLE) but was ultimately diagnosed with SAVI. The patient exhibited signs of interstitial lung disease and cutaneous manifestations before the age of 1 year and continued to have recurrent fever accompanied by pulmonary infiltrates. Based on positive findings for antibodies associated with SLE, such as antinuclear antibodies and anti-double-stranded DNA, the pulmonary involvement was considered a manifestation of SLE. Another significant symptom was recurrent skin ulceration, which led to partial spontaneous amputation of most of the toes due to inflammation. Given the early onset of interstitial lung disease, severe skin ulcers, and symptoms resembling SLE, autoinflammatory syndrome, especially SAVI was suspected. Following confirmation by genetic testing at age 29 years, the patient was started on tofacitinib, a Janus kinase inhibitor. Despite the prolonged use of multiple immunosuppressive therapies, the patient's lung condition continued to worsen, ultimately requiring lung transplantation. This observational report highlights the importance of considering SAVI as a potential diagnosis when manifestations of interstitial lung disease are observed during infancy. Early proactive treatment is crucial for lung involvement, as this can have long-term effects on patient's prognosis.
PubMed: 38957365
DOI: 10.4078/jrd.2023.0075