International Journal of Immunopathology and Pharmacology最新文献

This study aimed to characterize micronutrient deficiencies, including iron, ferritin, folic acid, vitamin D, zinc (Zn), vitamin B₁₂, and copper, in patients with celiac disease, and evaluated the effects of these deficiencies on selected hematological parameters, including hemoglobin and mean corpuscular volume (MCV). Celiac disease (CeD), an immune-mediated disorder affecting the small bowel, is associated with genetic factors and micronutrient deficiencies. This meta-analysis was performed in accordance with the PRISMA guidelines. Literature searches of multiple databases retrieved 4140 studies, of which 45 were selected. Risk of Bias was performed in accordance with the STROBE checklist. Meta-analysis revealed a significant difference in hemoglobin levels between patients with CeD and controls (standardized mean difference (SMD) -0.59 (95% confidence interval (CI) -0.8459 to -0.3382); P = 0.0003). Iron levels were lower in patients with CeD (SMD ≈ -0.4 (95% CI -0.7385 to -0.0407); P = 0.0334), as were ferritin (SMD -0.6358 (95% CI -0.8962 to -0.3755); P = 0.0002), folic acid (SMD -0.5446 (95% CI -0.9749 to -0.1142); P = 0.0187), and vitamin D (SMD -0.4011 (95% CI -0.8020 to -0.0001); P = 0.0499) levels, while Zn levels were significantly reduced (SMD -1.1398 (95% CI -2.0712 to -0.2084); P = 0.0242). No significant differences were found in MCV, or copper or vitamin B₁₂ levels between patients with CeD and controls. This study highlighted significantly higher micronutrient deficiencies in patients diagnosed with CeD than in controls, underscoring the importance of systematic nutritional assessment and multidisciplinary management to address micronutrient deficiencies and minimize negative health impact(s).

Background: Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory abilities, particularly in a milieu of hyperactive immune system, through secreting a number of cytokines, growth factors, bioactive compounds and peptides, and by cell-cell contact. During viral infection, failure of immuno-neutralization of the viral particles, recruits T-lymphocytes (T-cells) that clear the virally-infected cells. MSCs greatly potentiate T-cells anti-viral activity.

Objective: The objective of this study is to assess the ability of the cytokine-primed MSCs to activated T-cells, towards an antiviral application.

Method: Human umbilical cord MSCs (UC-MSCs) were isolated from Wharton Jelly of a consented donor. UC-MSCs were primed with interferon (INF)-γ and transforming growth factor (TGF)-β1. Peripheral blood T-cells were isolated using mini-max and CD3+ population was purified using anti-CD3 immuno-magnetic beads. Naïve or primed MSCs were co-cultured with naïve and phytohemagglutinin (PHA)-activated CD3+ T-cells. T-cell activation was evaluated by changes in their rate of proliferation by cell count, flowcytometric immuno-phenotyping for CD25 expression, and IL-6 secretion in the conditioned medium.

Results: The findings revealed that CD3+ T-cells count nonsignificant differed comparing the five experimental groups; Naïve MSCs, Naïve T cells, coculture with naïve MSCs, coculture with primed MSCs, and upon phytohemagglutinin-activation, despite a nonsignificant reduction of proliferation in the last two groups' coculture. Only the coculture with the primed MSCs showed significant activation of T-cells assessed as CD25 expression compared to the other groups (p < 0.001 and p = 0.002, respectively). The undetectable levels of IL-6 in the conditioned medium of naïve MSCs, turned markedly high after their cytokine-priming (p < 0.001), reaching nonsignificant difference compared to naïve T-cells. Compared to naïve MSCs, naïve T-cells secreted considerable amounts of IL-6 (p < 0.001). Incubation of naïve MSCs with phytohemagglutinin-activated T-cells further the secretion of IL-6, to a level significantly higher than all of the aforementioned three groups; naïve MSCs, naïve T-cells and primed MSCs (p < 0.001, p = 0.0194, and p < 0.001, respectively). However, coculture of the cytokine-primed MSCs with phytohemagglutinin-activated T-cells dampened IL-6 secretion to a level that was significantly lower than that observed with naïve MSCs-phytohemagglutinin-activated T-cells coculture (p < 0.001).

Conclusion: The cytokine-primed UC-MSCs significantly upregulated CD25+ expression on T-cells, while hindering IL-6, without affecting their proliferation rate. This may point to potentially stronger antiviral effects, while alleviating the viral infection-induced cytokine storm.

Crohn's disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-α). Adalimumab, targeting TNF-α, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA-Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes ATG16L1, CD96, and CD155. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (P = 0.003), with moderate agreement (Lin's correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (P = 0.0125). The genotypic evaluation revealed significant associations for the CD96 CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. ATG16L1 CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for CD96 and ATG16L1 with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab.

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined the effect of exogenous anti-GFAP antibodies on SCI pathology, pain-associated molecular changes, and behavior.

Methods: Anti-GFAP or IgG was administered at 7- and 14-days post-injury. Immunohistochemistry was performed to measure the relative levels of calcitonin gene-related peptide (CGRP), and inflammatory proteins in dorsal horn tissue. To assess the development of neuropathic pain, the von Frey test and the Mechanical Conflict-Avoidance Paradigm (MCAP) were performed.

Results: CGRP immunoreactivity was significantly higher in the anti-GFAP-treated injured rats compared to control SCI IgG-treated rats. As anticipated, SCI rats had a lower pain threshold at 1- and 2-months post-injury compared to laminectomy-only controls. However, pain withdrawal threshold was not significantly affected by post-injury administration of the anti-GFAP. Operant testing revealed that SCI rats treated with the anti-GFAP had a trending increase in pain sensitivity.

Conclusion: Taken together, these data suggest that autoantibodies to GFAP following SCI may contribute to developing pain states following SCI.

Objective: This meta-analysis aims to systematically evaluate the associations of four specific Single Nucleotide Polymorphisms (SNPs)-rs712829, rs712830, rs11568315, and rs884225-located in the promoter, intronic, and 3' untranslated regions (3'UTR) of the EGFR gene, with lung cancer risk.

Introduction: The associations between EGFR gene polymorphisms and lung cancer risk is a topic of ongoing debate, which is still deemed controversial. Despite numerous studies, results are inconsistent.

Methods: We conducted a comprehensive literature search across the PubMed, Science Direct, and Web of Science databases to identify relevant case-control studies examining the association between EGFR gene polymorphisms and lung cancer risk.

Results: From an initial pool of 26,959 articles, 10 case-control studies were included, involving 2471 lung cancer patients and 4489 controls. A significant association between rs712829 and increased lung cancer risk was found across multiple genetic models. Under the allelic contrast model (G vs T), the OR was 1.31 (95% CI = [1.02; 1.68], p < 0.05), the dominant model (GG + GT vs TT) showed an OR of 1.69 (95% CI = [1.07; 2.67], p < 0.05), the homozygote model (GG vs TT) yielded an OR of 1.70 (95% CI = [1.00; 2.88], p < 0.05), and the heterozygote model (GT vs TT) had an OR of 1.64 (95% CI = [1.01; 2.66], p < 0.05). No significant associations were found for rs11568315, rs712830, and rs884225.

Conclusion: The findings from the current meta-analysis confirm that rs712829 within the EGFR gene is significantly associated with lung cancer risk according to the allele, dominant, homozygote and heterozygote models.

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls (P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels (P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores (P-values <0.05) but did not correlate significantly with tenosynovitis scores (P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients (P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.

Background: Alteplase intravenous thrombolysis is effective for treating acute ischemic stroke (AIS) within 4.5 h. Nevertheless, the prognosis remains poor for some patients.Objective: To investigate the risk factors for poor prognosis in patients undergoing intravenous thrombolysis with alteplase following AIS based on propensity score matching and to develop a predictive model.Result: Multivariate logistic regression analysis showed that baseline blood glucose (OR = 1.20, 95%CI, 1.03-1.39), baseline NIH Stroke Scale score (OR = 1.23, 95%CI, 1.12-1.35), and hyperlipidemia (OR = 6.60, 95%CI 1.74-25.00) were risk factors for poor prognosis in patients with AIS undergoing alteplase intravenous thrombolysis. Using these factors, a nomogram model was constructed for predicting patient prognosis at 3 months. The areas under the receiver operating characteristic curve (AUCs) of the training and validation groups were 0.792 (95CI% 0.715-0.870) and 0.885 (95CI% 0.798-0.972), respectively, showing good differentiation. The Hosmer Lemeshow goodness-of-fit test showed that the model had good fit. The calibration curve fitted well with the ideal curve, and the decision curve analysis curve showed that the model had good clinical applicability when the threshold probability was between 10%-80%.Conclusion: The established nomogram could successfully predict the 3-month prognosis of patients with AIS after undergoing alteplase intravenous thrombolysis. The model thus has clinical application value.

Objective: This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD).

Method: Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation.

Results: Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12 h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12 h.

Conclusion: It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.

Introduction: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis.

Methods: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining.

Results: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques.

Conclusion: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes acute coronavirus disease-19 (COVID-19) that has emerged on a pandemic level. Coronaviruses are well-known to have a negative impact on the lungs and cardiovascular system. SARS-CoV-2 induces a cytokine storm that primarily targets the lungs, causing widespread clinical disorders, including COVID-19. Although, SARS-CoV-2 positive individuals often show no or mild upper respiratory tract symptoms, severe cases can progress to acute respiratory distress syndrome (ARDS). Novel CoV-2 infection in 2019 resulted in viral pneumonia as well as other complications and extrapulmonary manifestation. ARDS is also linked to a higher risk of death. Now, it is essential to develop our perception of the long term sequelae coronavirus infection for the identification of COVID-19 survivors who are at higher risk of developing the chronic lung fibrosis. This review study was planned to provide an overview of the effects of SARS-CoV-2 infection on various parts of the respiratory system such as airways, pulmonary vascular, lung parenchymal and respiratory neuromuscular system as well as the potential mechanism of the ARDS related respiratory complications including the lung fibrosis in patients with severe COVID-19.