International Journal of Immunopathology and Pharmacology最新文献

Celiac disease (CD) is an immune-mediated disorder with premature apoptosis occurring along the entire crypt-villous axis. H2AX is the end product of the intrinsic apoptotic pathway. This is the first study to assess apoptotic body counts (ABC) by H&E and apoptotic indices (AI) by immunohistochemistry (IHC) in pediatric CD. The aim of the current study was to evaluate ABC in pediatric patients with CD prior to and following institution of a gluten free diet (GFD). Sixty-three pediatric endoscopic duodenal samples were assessed and divided into three groups. A total of 21 samples from treatment naïve CD patients, 21 from the same patients after instituting a GFD, and 21 from non-celiac patients as a control group. Histopathological evaluation of ABC by H&E, and immunohistochemistry assessment of apoptotic indices (AI) by H2AX antibody were performed. The mean maximum ABC and AI were significantly higher in treatment naïve CD than in GFD and control samples. These values were also significantly higher in treatment naïve Marsh 3C (flat) than in Marsh 1, 2, 3A, and 3B (non-flat) CD cases. GFD samples with persistent flat lesions had significantly higher ABC and AI than GFD non-flat cases. ROC analysis of the mean maximum ABC and AI of treatment naïve CD cases had a statistically significant predictive potential for persistent villous atrophy at a cut-off level ⩾6.61 (P = 0.008) and ⩾105.4 (P = 0.003), respectively. Histopathological evaluation of crypt apoptotic bodies could provide predictive potential for continued villous atrophy following GFD.

COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.

Objectives: Vaccination rollout against COVID-19 has started in developed countries in early December 2020. Mass immunization for poor or low-income countries is quite challenging before 2023. Being a lower-middle-income country, Bangladesh has begun a nationwide COVID-19 vaccination drive in early February 2021. Here, we aimed to assess the opinions, experiences, and adverse events of the COVID-19 vaccination in Bangladesh.

Methods: We conducted this online cross-sectional study from 10 February 2021, to 10 March 2021, in Bangladesh. A self-reported semi-structured survey questionnaire was used using Google forms. We recorded demographics, disease history, medication records, opinions and experiences of vaccination, and associated adverse events symptoms.

Results: We observed leading comorbid diseases were hypertension (25.9%), diabetes (21.1%), heart diseases (9.3%), and asthma (8.7%). The most frequently reported adverse events were injection site pain (34.3%), fever (32.6%), headache (20.2%), fatigue (16.6%), and cold feeling (15.4%). The chances of having adverse events were significantly higher in males than females (p = 0.039). However, 36.4% of respondents reported no adverse events. Adverse events usually appeared after 12 h and went way within 48 h of vaccination. Besides, 85.5% were happy with the overall vaccination management, while 88.0% of the respondents recommended the COVID-19 vaccine for others for early immunization.

Conclusion: According to the present findings, reported adverse events after the doses of Covishield in Bangladesh were non-serious and temporary. In Bangladesh, the early vaccination against COVID-19 was possible due to its prudent vaccine deal, previous mass vaccination experience, and vaccine diplomacy.

Sepsis is a leading cause of death worldwide, despite the use of multimodal therapies. Common antibiotic regimens are being affected by a rising number of multidrug-resistant pathogens, and new therapeutic approaches are therefore needed. Antibiotics have immunomodulatory properties which appear to be beneficial in the treatment of sepsis. We hypothesized that the last-resort antibiotics vancomycin (VAN) and daptomycin (DMC) modulate cell migration, phagocytosis, and protein cytokine levels in a murine model of lipopolysaccharide (LPS)-induced sepsis. Ten to twelve-week-old C57BL/6 mice (n = 4-6 animals per group) were stimulated with LPS for 20 h, followed by the administration of VAN or DMC. The outcome parameters were leukocyte accumulation and effector function. Quantification of the immune cells in the peritoneal lavage was performed using flow cytometry analysis. Phagocytosis was measured using pHrodo E. coli BioParticles. The response of the cytokines TNFα, IL-6, and IL-10 was measured in vitro using murine peritoneal macrophages stimulated with LPS and VAN or DMC. VAN decreased both the peritoneal macrophage and the dendritic cell populations following LPS stimulation. DMC reduced the dendritic cell population in the peritoneal cavity in LPS-infected mice. Both antibiotics increased the phagocytic activity in peritoneal macrophages, but this effect was diminished in response to LPS. Phagocytosis of dendritic cells was increased in LPS-infected animals treated with VAN. VAN and DMC differently modulated the levels of pro-and anti-inflammatory cytokines. In a murine model of LPS-induced sepsis, VAN and DMC exhibit immunomodulatory effects on cells involved in innate immunity. The question of whether these antibiotics exhibit synergistic effects in the treatment of septic patients, beyond their bactericidal properties, should be further evaluated in future studies.

Chronic inflammation in asthmatics is initiated/exacerbated by many environmental factors, such as bacterial lipopolysaccharide and allergens. Phospholipase A₂ and histone acetyltransferase/deacetylases are enzymes involved in inflammatory process, particularly in lipid inflammatory mediators production and control of transcription of many inflammatory genes, respectively. The aim of the study was to identify differences in the inflammatory process in patients with severe and non-severe asthma, taking as a criterion expression of two groups of enzymes: phospholipases A₂ and histone acetyltransferases/deacetylases. Thirty-two patients with severe, non-severe atopic to house dust mite asthmatics and 14 healthy volunteers were recruited. Peripheral blood mononuclear cells were stimulated with Dermatophagoides pteronyssinus allergen (nDer p1) and bacterial lipopolysaccharide (LPS). The expression of phospholipases A₂ and histone acetyltransferases and deacetylases were assessed using TaqMan Low Density Array Cards. The protein expression was analyzed with immunoblot. Increased expression of phospholipase A2 Group IVC (PLA2G4C) and cytosolic phospholipase A2 gamma (cPLA₂γ) protein was observed in peripheral blood mononuclear cells (PBMC) from severe asthmatics in response to LPS and nDer p1, compared to non-severe asthmatics. nDer p1-stimulated PBMC from severe asthmatics exhibit induced expression of HDAC1 and similar trend was observed in protein concentration. Decreased expression of EP300 occurred in PBMC of severe asthmatics. PBMC from non-severe asthmatics showed decreased expression of HDAC2 and PLA2G15 after LPS treatment. In conclusion, in response to LPS and dust mite allergen, PBMC from severe and non-severe asthmatics modulate expression of selected phospholipase A₂, histone acetyltransferases and deacetylases, while increased expression of cPLA₂γ characterizes PBMC response from severe asthmatics.

Allergic rhinitis (AR) and allergic asthma (AA) exhibit similar inflammatory response in the airways. However, the remodelling is more extensive in the lower airways, suggesting that the inflammation itself is not sufficient for allergic phenotype. We aimed to analyse whether the expression of selected 27 inflammatory and fibrosis-related proteins may be altered in AR and AA in the paediatric population and whether the expression pattern is either similar (due to the inflammation) or disease-specific (due to the remodelling). We analysed 80 paediatric subjects: 39 with AA, 21 with AR and 20 healthy children. The diagnosis of AR and AA was based on clinical manifestation, lung function, positive skin prick tests and increased immunoglobulin E levels. Serum levels of selected inflammatory proteins were measured with custom Magnetic Luminex Assay. Statistical analysis was performed in Statistica v.13. CCL2/MCP1, GM-CSF, gp130 and periostin concentrations were significantly lower, whereas IL-5 levels were higher in AA compared to the control group. CD-40L, CHI3L1/YKL-40, EGF, GM-CSF and periostin levels were significantly decreased in patients with AR than in the control group. Comparison of AA and AR patients revealed significant changes in CHI3L1/YKL-40 (P = 0.021), IL-5 (P = 0.036), periostin (P = 0.013) and VEGFα (P = 0.046). Significantly altered proteins were good predictors to distinguish between AA and AR (P < 0.001, OR 46.00, accuracy 88.57%). Our results suggest that the expression of four fibrotic proteins was significantly altered between AA and AR, suggesting possible differences in airway remodelling between upper and lower airways.

Probiotics are microorganisms that confer health benefits to host. Well-known examples include Bifidobacterium and Lactobacillus species. In recent years, interest in promoting our health with probiotics has grown as life expectancy and health awareness has increased. However, some concerns for safety and stability exist for these live organisms. Thus, "postbiotics" and "paraprobiotics," non-viable heat-killed microbial cells or cell fractions that retain health benefits, are increasingly favored. Unfortunately, little information on clinical efficacy and mechanisms of action is available compared with many available probiotics. Lacticaseibacillus (previous name Lactobacillus) paracasei MCC1849 is a commonly used lactic acid bacterial strain in Japan that displays immuno-modulatory effects in humans in non-viable heat-killed form. This review discusses health benefits of heat-killed L. paracasei MCC1849 immune modulation and offers a theoretical basis for its mechanisms of action. We also discuss the feasibility of using heat-killed probiotics for application in food products.