Inflammation In Asthma Research Articles

Potential of Ficus religiosa Linn. Flavonoids in Management of Allergic Asthma

Humans have been using medicinal plants as a source of medicine for thousands of years. Truth be told, ancient man was completely reliant on plants for all of his medical needs, including recovery, prevention, and other types of medications, and has done so for millennia. Many plants and herbs hold their prestigious position in the field of medicine among which Ficus religiosa belonging to the family Moraceae is the vital one. Recent studies have reported that Ficus religiosa is used in the traditional medicine to relieve about 50 types of disorders including diabetes, diarrhoea, epilepsy inflammatory disorders, and gastric problems, sexual and infectious disorders. Antihistaminic principles are known to be useful in the treatment of asthma; hence, in the present work, the antihistaminic activity of an ethanol extract of Ficus religiosa was assessed using various methods. The results showed that the ethanol fractions inhibits clonidine-induced catalepsy as well as asthmatic inflammation. This suggests that the inhibition is through an antihistaminic action and that there is no role of dopamine. Hence, we concluded that the ethanol extract has significant antihistaminic activity. The flavonoid derivatives identified from ethanol fractions of leaves of Ficus religiosa may showed potential as a antihistaminic activity. So in future the plant Ficus religiosa isolated these flavonoids may lead significant role in the treatment of asthma.

Bronchial Asthma and Mucociliary Clearance - A Bidirectional Relationship

: The integrity of the airway epithelium plays an important role in the defence against pathogens and various immunogenic stimuli from the external environment. Properly functioning mucociliary clearance is an indispensable part of the respiratory system defence and it relies on adequate viscoelastic properties of mucus, as well as the intact function of a significant number of healthy ciliated cells. The movement of the cilia can be affected by many endogenous and exogenous factors. Complex mucociliary clearance dysfunction can be seen as a part of the respiratory system inflammation. Bronchial asthma is one of the most common inflammatory diseases of the respiratory system. It is characterised by structural and functional changes in the airways. The last decades of bronchial asthma research point to asthmatic inflammation as the cause of airway remodelling with subsequent impairment of mucociliary transport function. Changes in the respiratory epithelium in patients with bronchial asthma include hypertrophy of secretory cells, overproduction of mucus, increase in mucus viscosity, decline of ciliated cells, decrease of ciliary beat frequency, and more. Cytokines of T2-high type of asthmatic inflammation, such as interleukin IL-13 and IL-4, have been shown to contribute to these changes in the airway epithelium significantly. There is strong evidence of cytokine-induced overexpression of important transcription factors, which results in hyper- and metaplasia of secretory cells and also transdifferentiation of ciliary cells. Impaired mucociliary clearance increases the risk of airway infection and contributes to the worsening of bronchial asthma control.

Acupoint Autohemotherapy Alleviates Airway Inflammation in Asthmatic Rats via Upregulating Expression of Hemeoxygenase-1.

Acupoint autohemotherapy (AA), a therapeutic technique involving the subcutaneous injection of autologous blood into acupoints, has been empirically validated as safe and effective for treating asthma by alleviating symptoms and decreasing acute attacks, though its mechanism is not well understood. The role of heme oxygenase-1 (HO-1) in AA-induced suppression of asthmatic airway inflammation is examined. Twenty rats were assigned randomly to four groups, namely the Control, OVA, OVA + AA, and (OVA + Snpp) + AA. Rats in the OVA + AA and (OVA + Snpp) + AA received autologous blood injections into acupoints (BL13 and BL23) following OVA challenge. Rats in the (OVA + Snpp) + AA were concurrently subjected to intraperitoneal injections of Snpp, a inhibitor of HO-1. Airway inflammation was evaluated through HE staining, while the concentrations of cytokines in BALF were quantified using ELISA. The mRNA and protein levels of RORγt (Th17-specific transcription factor), Foxp3 (Treg-specific transcription factor), and HO-1 in lung tissue were assessed through qRT-PCR and WB. HE staining indicated that airway inflammation was alleviated in the OVA + AA. The OVA + AA displayed significantly lower counts of total cells and eosinophils in the BALF compared to both the OVA and (OVA + Snpp) + AA. The ELISA demonstrated a significant decrease in levels of pro-inflamatory cytokines (IL-4, IL-17A), and an increase in levels of anti-inflamatory cytokines (IFN-γ, IL-10), in the OVA + AA when compared to both OVA and (OVA + Snpp) + AA. The qRT-PCR and WB analyses revealed an upregulation of HO-1 and Foxp3 expression, and a downregulation of RORγt expression, in the OVA + AA when compared to OVA and (OVA + Snpp) + AA. The involvement of HO-1 in the underlying mechanism responsible for the anti-inflammatory effects of AA is evident.

Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma.

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.

The gut microbiota modulates airway inflammation in allergic asthma through the gut-lung axis related immune modulation: A review.

The human gut microbiota is a vast and complex microbial community. According to statistics, the number of bacteria residing in the human intestinal tract is approximately 10 times that of total human cells, with over 1,000 different species. The interaction between the gut microbiota and various organ tissues plays a crucial role in the pathogenesis of local and systemic diseases, exerting a significant influence on disease progression. The relationship between the gut microbiota and intestinal diseases, along with its connection to the pulmonary immune environment and the development of lung diseases, is commonly referred to as the "gut-lung axis." The incidence of bronchial asthma is rising globally. With ongoing research on gut microbiota, it is widely believed that intestinal microorganisms and their metabolic products directly or indirectly participate in the occurrence and development of asthma. Based on the gut-lung axis, this review examines recent research suggesting that the intestinal microbiota can influence the occurrence and progression of allergic asthma through the modulation of cytokine immune balance and mucosal integrity. Though the precise immune pathways or microbial species influencing asthma through the gut-lung axis are still under exploration, summarizing the immune modulation through the gut-lung axis in allergic asthma may provide insights for the clinical management of the condition.

Влияние избыточной массы тела и ожирения на спирометрические, гематологические показатели, уровень общего иммуноглобулина Е и интерлейкина-6 в сыворотке крови у детей и подростков с бронхиальной астмой

There is undoubtedly insufficient number of studies dedicated to the interleukin-6 (IL-6) in blood serum of children and adolescents with bronchial asthma (BA) and those are contradictory. Connection between the IL-6 serum level and systemic markers of type 2 inflammation in BA in children and adolescents depending on the nutritional status remains a subject to discussion as well. The purpose of this research was to study the effect of excess body weight (BW) and obesity on spirometric, hematological parameters, total immunoglobulin E (IgE), IL-6 levels in blood serum of children and adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 76 adolescents aged 6 to 17 y/o (75% (57) boys) with BA was conducted. All were measured for anthropometric and spirometric parameters, body composition, hematological parameters, total IgE and IL-6 levels in blood serum. Dysanapsis was diagnosed when three conditions were simultaneously met: 1. high or high-to-normal zFVC (above 0.674), 2. normal zFEV1 (above -1.645), and 3. low FEV1/FVC index (below 80%). Results: the number of monocytes (109/l) in peripheral blood and the serum IL-6 level (pg/ml) were statistically significantly higher in the group of patients with overweight and obesity compared to patients with underweight/normal BW (0.55 [0.49; 0.77] v 0.51 [0.42; 0.58], p=0.043 and 1.99 [1.20; 5.78] v 1.28 [0.31; 2.43], p=0.002, respectively). In patients with excess BW and obesity, an inverse statistically significant relationship was found between the serum IL-6 level, zFEV1/FVC and the dysanapsis ratio (R=-0.53, p=0.009, R=-0.61, p=0.002, respectively). Conclusion: formation of an obstructive pattern in children and adolescents with BA with excess BW and obesity may be associated with non-T2-dependent inflammatory mechanisms.

NLRP3 regulates ferroptosis via the JAK2/STAT3 pathway in asthma inflammation: Insights from in vivo and in vitro studies

BackgroundFerroptosis, an iron-dependent form of cell death, plays a pivotal role in the pathologic progression of asthma. Electroacupuncture (EA) has demonstrated considerable efficacy in mitigating asthma airway inflammation, although its underlying mechanisms remain partially elucidated. MethodsWe investigated the regulatory effect of NLRP3 on ferroptosis using a lipopolysaccharide (LPS)-induced inflammation model in BEAS-2B cells, where NLRP3 expression was modulated with si-RNA and overexpression plasmids. The levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified. We also assessed NLRP3 and JAK2/STAT3 pathway-related proteins, and evaluated lipid peroxidation, mitochondrial membrane potential (ΔΨm), and antioxidant system functionality. In vivo, we examined the impact of EA on ferroptosis and airway inflammation by modulating NLRP3 activation. Asthma inflammation severity was evaluated using H&E, Masson, and PAS staining, alongside ELISA. NLRP3 and JAK2/STAT3 pathway-related proteins, as well as ferroptosis indicators, were also analyzed. The mechanism by which NLRP3 activates ferroptosis was investigated through in vitro assays. ResultsLPS exposure resulted in increased intracellular inflammatory cytokines, and activation of the NLRP3 and JAK2/STAT3 pathways, leading to enhanced lipid peroxidation, decreased ΔΨm, and disruption of antioxidant system balance, ultimately inducing ferroptosis. Si-NLRP3 countered the effects of LPS, whereas oe-NLRP3 exacerbated symptoms. In vivo studies revealed that EA reduced airway inflammation, inhibited NLRP3 activation, and decreased phosphorylation of JAK2/STAT3, effectively lowering ferroptosis-related indicators. Utilizing JAK2/STAT3 activators and inhibitors, we confirmed that NLRP3 mediates ferroptosis via the JAK2/STAT3 pathway. ConclusionsEA alleviates HDM-induced asthma, primarily through the inhibition of NLRP3 activation, which modulates the JAK2/STAT3 pathway and mediates ferroptosis.

Blood eosinophil count is associated with early atherosclerotic artery changes in asthma

ObjectiveAsthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma.MethodsWe assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (< 300/µl) and high (≥ 300/µl) blood eosinophil counts (BEC).ResultsWe enrolled 100 patients, 42 with a BEC of < 300 and 58 with a BEC of ≥ 300 n/µl. Patients with high BEC exhibited more severe disease, characterized, e.g., by a higher frequency of acute exacerbations (1.3 ± 2.1 vs. 2.6 ± 2.4 n/year, p = 0.005). Both groups presented similar profiles in terms of conventional cardiovascular risk. The high BEC group demonstrated elevated arterial stiffness, reflected by reduced radial strain (mean radial strain of the right CCA: 2.7 ± 1.4% for BEC ≥ 300 n/µl vs. 3.5 ± 1.7% for BEC < 300 n/µl, p = 0.008; left CCA: 2.6 ± 1.4% vs. 4.1 ± 2.2%, p < 0.001). A weak yet statistically significant negative correlation was observed between BEC and radial strain for the right CCA (R2 = 0.131, b=-0.001, p = 0.001) and left CCA (R2 = 0.086, b=-0.001, p = 0.015). However, the prevalence of cerebrovascular disease was similar in both groups (31,0% vs. 50,0%, p = 0.057).ConclusionWe identified a correlation between BEC and vascular stiffness, which supports the hypothesis that eosinophils may promote atherosclerosis.Clinical trial numberDue to the exploratory and predominantly retrospective nature of the study, trial registration was not conducted. The only prospective procedure conducted was the angiological sonography to evaluate the current state. No ensuing health-related interventions were performed specifically for this study.

Prospects of vaccination against pneumococcal infection based on the asthma phenotype

According to recent studies, bronchial asthma is characterized by a wide variability of the mechanisms of occurrence and progression. This heterogeneity is caused by patterns of predominant cells and inflammatory mediators, which determine differences in immunological parameters observed in patients with certain endotypes depending on the dominant type of mediators (high and low T2 inflammation). In long-term observations, a substantial research base has been accumulated justifying the effectiveness of vaccination against pneumococcal infection in patients with asthma. The vaccination decreases the frequency of exacerbations of the disease and hospitalizations in the short and medium term. However, these studies evaluated the asthma patients as a wholesome population, and it remains unexplored whether the effect of pneumococcal vaccines on asthma differs depending on the endotype of the disease and what are the mechanisms of such a differentiated effect.The aim of this work is to present the results of recent quality studies on changes in the profile of inflammatory asthma mediators under the action of immunobiological substances based on Streptococcus pneumoniae antigens, primarily from the vaccines.Conclusion. The asthma heterogeneity can lead to different clinical outcomes in pneumococcal infection and, respectively, the clinical effects of immunization in patients differentiate according to the nature of inflammation. In other words, the uniformity of the clinical effect of vaccination against pneumococcal infection in all patients in ongoing studies may represent the combined effect of molecular mechanisms regulating the specific activity of Th1-, Th2-, Th17-, NKT-, and Treg-cells. The results of studies proving the ability of pneumococcal vaccines to modulate the Th1-, Th2-, Th17-, Treg immune response in patients with asthma contributed to increased interest in developing new immunoregulatory therapeutic agents based on S. pneumoniae antigens.

Targeted DNase treatment of obstructive lung disease: a pilot randomised controlled trial

BackgroundSputum extracellular DNA(eDNA) is associated with disease severity in asthma and COPD and therefore emerging as a potential therapeutic target.ObjectiveTo investigate the effect of 10 days of recombinant human DNase(rhDNase) treatment of eDNA-high asthma and COPD, on sputum eDNA levels, neutrophil-related inflammation, lung function and symptoms.MethodsAdults with asthma (n=80) or COPD (n=66) were screened for the presence of high (&gt;20 µg·mL−1) sputum eDNA and those eligible [n=18 asthma, n=17 COPD] were randomised to a two-period crossover controlled trial consisting of daily nebulised rhDNase (2.5 mg/2.5 mL) or placebo (5 mL 0.9%saline) for 10 days, with a 2-week washout period. The primary outcome was sputum eDNA, and secondary outcomes included sputum neutrophil extracellular trap (NET)-related biomarkers, inflammatory cell counts, lung function and respiratory symptoms.ResultsAt screening, high eDNA was associated with significantly higher sputum total cell count, sputum colour score, and inflammation (HNP1-3, LL-37 and IL-1β) in both asthma and COPD compared to low eDNA groups. In asthma, participants with high eDNA were older, and had poorer lung function and asthma control compared to low eDNA. Administration of nebulised rhDNase significantly reduced sputum eDNA levels in both asthma (median(q1,q3) Pre: 48.4 (22.1,74.1); Post: 17.0 (5.0,31.0) µg·mL−1; p=0.022) and COPD (median(q1,q3) Pre: 39.3 (36.7,55.6); Post: 25.4 (11.3,38.6) µg·mL−1; p=0.044) compared to placebo. Symptoms, lung function and NET biomarkers remained unchanged. In asthma, there was a reduction in banded blood neutrophils (3.2(0,7.7) to 0.0 (0.0,1.5); p=0.044).ConclusionTargeted rhDNase treatment for 10 days effectively reduced sputum eDNA in eDNA-high asthma and COPD.

Immunologic aspects of asthma: from molecular mechanisms to disease pathophysiology and clinical translation.

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

Characterization of pesticide exposures and their associations with asthma morbidity in a predominantly low-income urban pediatric cohort in Baltimore City

BackgroundPesticides may impact respiratory health, yet evidence of their impact on pediatric asthma morbidity is limited, particularly among urban children. ObjectiveTo characterize pesticide biomarker concentrations and evaluate their associations with pediatric asthma morbidity among predominantly low-income, Black children in Baltimore City, USA. MethodsWe measured urinary concentrations of 10 biomarkers for pyrethroid insecticides (cyfluthrin:4F-3PBA, permethrin:3PBA), organophosphate insecticides (chlorpyrifos:TCPY, malathion:MDA, parathion:PNP, diazinon:IMPY), and herbicides (glyphosate:AMPA, GPS; 2,4-dicholorphenoxyacetic acid:2,4-D; 2,4,5-tricholorphenoxyacetic acid:2,4,5-T) among 148 children (5–17 years) with established asthma. Urine samples and asthma morbidity measures (asthma symptoms, healthcare utilization, lung function and inflammation) were collected every three months for a year. Generalized estimating equations were used to examine associations between pesticide biomarker concentrations and asthma morbidity measures, controlling for age, sex, race, caregiver education, season, and environmental tobacco smoke. In sensitivity analyses, we assessed the robustness of our results after accounting for environmental co-exposures. ResultsFrequently detected (≥90% detection) pesticide biomarker concentrations (IMPY, 3PBA, PNP, TCPY, AMPA, GPS) varied considerably within children over the follow-up period (intraclass correlation coefficients: 0.1–0.2). Consistent positive significant associations were observed between the chlorpyrifos biomarker, TCPY, and asthma symptoms. Urinary concentrations of TCPY were associated with increased odds of coughing, wheezing, or chest tightness (adjusted Odds Ratio, aOR, TCPY:1.60, 95% Confidence Interval, CI:1.17–2.18). Urinary concentrations of TCPY were also associated with maximal symptom days (aOR:1.38, CI:1.02–1.86), exercise-related symptoms (aOR:1.63, CI:1.09–2.44), and hospitalizations for asthma (aOR:2.84, CI:1.08–7.43). We did not observe consistent evidence of associations between the pesticide exposures assessed and lung function or inflammation measures. ConclusionAmong predominantly Black children with asthma, we found evidence that chlorpyrifos is associated with asthma morbidity. Further research is needed to assess the contribution of pesticide exposures to pediatric respiratory health and characterize exposure sources among vulnerable populations to inform targeted interventions against potentially harmful pesticide exposures.

NFATc1 in CD4+ T cells and CD11c+ dendritic cells drives TH2-mediated eosinophilic inflammation in allergic asthma

BackgroundAsthma, a chronic lung disease, is a significant public health problem worldwide. It is marked by increased Th2 response resulting in eosinophil accumulation. The pathophysiology of asthma involves various cell types, including epithelial cells, dendritic cells (DCs), innate lymphoid cells (ILCs), B cells, and effector cells. Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor for immune regulation, is known for its role in T cells and, more recently, in myeloid cells. However, the specific contributions of NFATc1 in T cells and DCs in the context of asthma are not well understood. ObjectiveExplore NFATc1’s role in T cells and dendritic cells in modulating Th2 immune responses within the pathophysiology of allergic asthma. MethodsMice lacking Nfatc1 in CD4+T cells or CD11c+ dendritic cells, were induced with asthma using house dust mite (HDM), enabling investigation into NFATc1's role in both cell types in experimental allergic asthma. Additionally, the study examined NFATc1 expression in these cells and its correlation with blood eosinophil levels in an adult asthma cohort. ResultsIn HDM-induced asthma model, we found that Nfatc1 deficiency either in CD4+ T cells or CD11c+ dendritic cells resulted in reduced Th2-driven eosinophilic inflammation, immunoglobulin E (IgE) levels, and mast cell presence in the lung of asthmatic mice. Nfatc1's absence in CD4+ T cells directly hampered Th2 cell polarization and functionality, whereas in CD11c+ dendritic cells, it affected DC differentiation and maturation, thereby weakening T cell priming, proliferation and subsequent Th2 differentiation. Correspondingly, translational research indicated significant correlations between CD4+NFATc1+ and CD11c+NFATc1+ cell populations and eosinophil levels in asthmatic patients, but not in healthy controls. ConclusionNFATc1 in T cells and dendritic cells modulate Th2-mediated eosinophilic inflammation in allergic asthma, which offering insights into asthma pathogenesis and identifying NFATc1 as a potential target for therapeutic intervention.

Contribution of Pseudomonas aeruginosa − mediated club cell necroptosis to the bias of type 17 inflammation and steroid insensitivity in asthma

IntroductionOpportunistic pathogen infection is one of the important inducements for asthma exacerbation. Pseudomonas aeruginosa (PA) is a kind of dominant pathogenic bacteria in the respiratory tract that is associated with severe asthma, but the underlying mechanisms still remains unclear. ObjectivesTo examine the role of PA infection in the bias of the inflammatory endotype in asthma and its effect on the sensitivity to steroid therapy. MethodsAn adjusted HDM (House Dust Mite) −induced asthma model with PA inoculation in the airway was utilized to mimic the process of opportunistic PA infection in asthma, focusing on the interaction between bacteria and epithelium. Dexamethasone administration in vivo was used to test the sensitivity to steroid therapy. ResultsIt was uncovered that PA could promote the loss of club cells in the necroptosis pattern through cellular CYP450 activation, leading to an imbalance of inflammatory response and steroid insensitivity. Club cell loss results in the activation of cellular E-cadherin/β-catenin axis in the rest of club cells for goblet metaplasia and mucus hypersecretion, as well as epithelial damage and GR downregulation for steroid resistance. For clinical applications, the necroptosis inhibitor Nec-1 can effectively relieve the pathological symptoms of asthma in vivo. Meanwhile, CCSP administration in the airway can regulate the pulmonary inflammation and restore the steroid sensitivity in asthma. ConclusionThese experiments provide a novel mechanism of concurrent PA infection in asthma through club cell necroptosis and the pathological consequences. Nec-1 treatment and CCSP supplementation may be possible therapeutic strategies for asthma treatment.

Rheumatic adverse effects with biologics targeting type 2 inflammation in severe asthma: a VigiBase study

Biologics in severe asthma are associated with an excess reporting of rheumatic diseases and rheumatic symptoms in the WHO database. The profile of rheumatic adverse events varies according to biologics and their mechanisms of action.

Correlation of Biochemical Markers with Chest CT Severity Index and Oxygen Saturation in Moderate to Severe COVID-19 Patients: A cross-sectional study

Introduction: COVID-19, a global pandemic, has been linked to biochemical parameters such as Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Total Leucocyte Count (TLC), Neutrophil/Lymphocyte Ratio (NLR), Lactate Dehydrogenase (LDH), and liver function tests, which correlate with disease severity. Prothrombotic markers like D-Dimer and Fibrinogen levels, along with the CT Severity Index (CTSI) indicating lung involvement, are associated with clinical worsening. This study aims to observe biochemical and chest radiological profiles in moderate to severe COVID-19 patients and explore any correlations between them. Methodology: A hospital-based cross-sectional observational study was conducted at a Medical College and Hospital in Kolkata, involving 80 symptomatic COVID-19 patients with SpO₂ ≤94%. Patients with liver, kidney, chronic inflammatory diseases, COPD, malignancy, or asthma were excluded. Results: Out of 80 patients, 29 had moderate and 51 had severe illness. Statistically significant differences were observed in TLC, ESR, CRP, AST, ALT, A:G ratio, LDH, Fibrinogen, and D-Dimer between moderate and severe cases. The CTSI correlated significantly with TLC, NLR, CRP, AST, ALT, A:G ratio, LDH, Fibrinogen, and D-Dimer. CTSI values also differed significantly between moderate and severe COVID-19 cases. Conclusion: Biochemical markers such as ESR, TLC, CRP, liver enzymes, LDH, D-Dimer, and Fibrinogen can help predict disease severity. These markers also correlate with radiological severity in COVID-19.

Preventive Effects of Probiotics on Asthmatic Lung Inflammation in an Ovalbumin-Induced Murine Model

Preventive Effects of Probiotics on Asthmatic Lung Inflammation in an Ovalbumin-Induced Murine Model

β-arrestin2: an emerging player and potential therapeutic target in inflammatory immune diseases.

β-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that β-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-β pathways of non-GPCRs. Earlier studies have identified that β-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, β-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of β-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of β-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases.

Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis.

Although many susceptibility loci for IgA nephropathy (IgAN) have been identified, they only account for 11.0% of the overall IgAN variance. We performed a large genome-wide meta-analysis of IgAN in Han Chinese with 3616 cases and 10 417 controls to identify additional genetic loci of IgAN. Considering that inflammatory bowel disease (IBD) and asthma might share an etiology of dysregulated mucosal immunity with IgAN, we performed cross-trait integrative analysis by leveraging functional annotations of relevant cell type and the pleiotropic information from IBD and asthma. Among 8 669 456 imputed variants, we identified a novel locus at 4p14 containing the long noncoding RNA LOC101060498. Cell type enrichment analysis based on annotations suggested that PMA-I-stimulated CD4+CD25-IL17+ Th17 cell was the most relevant cell type for IgAN, which highlights the essential role of Th17 pathway in the pathogenesis of IgAN. Furthermore, we identified six more novel loci associated with IgAN, which included three loci showing pleiotropic effects with IBD or asthma (2q35/PNKD, 6q25.2/SCAF8, and 22q11.21/UBE2L3) and three loci specific to IgAN (14q32.32/TRAF3, 16q22.2/TXNL4B, and 21q21.3/LINC00113) in the pleiotropic analysis. Our findings support the involvement of mucosal immunity, especially T cell immune response and IL-17 signal pathway, in the development of IgAN and shed light on further investigation of IgAN.

Exploring CD26-/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4+ T cell subset expressing archetypical granulocyte proteins.

Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26-/lo, CD26int and CD26hi subsets within different lymphocyte populations. The proportion of CD26-/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4+CD26-/lo Teff cell subset by LC-MS/MS and immunofluorescence. Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4-CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26-/lo subsets. Specifically, CD4+CD26-/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes. There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26-/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.