Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease with difficult management, affecting the quality of life. Stem cell therapy has been proven to have regenerative ability. Using the existing stem cell therapy and modifying it, the current study aims to evaluate the effect of umbilical cord-derived mesenchymal stem cells (UCMSC), condition media (CM), and UCMSC and CM preconditioned with methotrexate, reservetrol, and vitamin D for its ability to manage T1DM in Swiss albino mice.

Materials & methods: Disease condition was established in the animals by using a diabetesinducing agent streptozotocin (STZ). Then the animals were grouped into normal control, disease control, standard, and test groups; and the treatments were given accordingly. The total study period for this experiment was 28 days. During this period, the animals were supervised for blood glucose levels, food-water intake, and body weight twice a week. At the end of 28 days, the biochemical estimations for serum insulin level, C-peptide, pro-inflammatory cytokines, and anti-inflammatory cytokines level were done. Also, histopathology of the pancreas was performed.

Results: The test groups showed a significant decline in the blood glucose level, an increase in C-peptide level, and a decrease in pro-inflammatory cytokines as compared to the disease group. A statistically significant change was not observed within the groups in terms of serum insulin and anti-inflammatory cytokine levels. There were improvements in diabetic symptoms in treatment groups, such as polyphagia, polydipsia, and weight loss. Treatment groups also showed pancreatic regeneration, indicating improved insulin secretion.

Conclusion: In the present study, we concluded that UCMSC, CM, and UCMSC and CM preconditioned with synthetic and natural immunosuppressants and immunomodulators have the ability to regenerate damaged pancreatic beta cells and have an antidiabetic activity, along with an immunomodulating effect. This therapy is a promising choice for future research.

This study provides a comprehensive bibliometric analysis of global research on urticaria, aiming to chart its progression, assess its relevance, and explore the roles of oxidative stress, inflammation, and immunity in its pathogenesis. Additionally, by analyzing data from PubMed and Scopus, we mapped research trends, identified leading authors and institutions, and examined global collaboration patterns. We also evaluated the impact of oxidative stress, inflammation, and immunity on urticaria and assessed the roles of both conventional and traditional medicine in its management. The results highlight the evolution of urticaria research, key contributors, thematic developments, and collaborative networks. This study offers a detailed bibliometric profile and thematic map, including insights into effective authors, prominent keywords, and significant research patterns. The findings are valuable for medical researchers, providing an updated overview of current themes and gaps, and are also beneficial for healthcare decision-makers by summarizing relevant information for strategic planning and fostering new collaborations. Additionally, the study integrates biological aspects related to urticaria with insights into traditional treatments, contributing to both research and practical management strategies.

Psoriasis (PsR), a chronic autoimmune disorder, affects millions of individuals globally and has a substantial impact on their quality of life. This complex condition involves intricate molecular networks and signaling pathways, making the development of effective treatments a significant challenge. Moreover, to advance treatment options, precise targeting of cells through the identification of protein biomarkers in PsR has emerged as a promising field of research for both fundamental and clinical scientists. These protein components provide valuable insights into the underlying mechanisms of the disease and can serve as indicators of treatment response. Furthermore, by identifying specific biocomponents, researchers can develop targeted therapeutics that address the molecular abnormalities driving PsR. The use of biologics as potential targets for improving treatment efficacy is a significant focus in PsR research. Biologics, which include monoclonal antibodies and fusion proteins, specifically target key molecules involved in the immune response, such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL). These targeted therapies have demonstrated substantial efficacy in managing PsR by modulating the immune system and reducing inflammation. Recent advancements in moleculartargeted therapies utilizing biologics or small-molecule inhibitors have contributed to improving patient outcomes. This review aims to summarize the recent discoveries and insights regarding biocomponents and their importance in treating PsR, encompassing both its inflammatory and dermatological aspects. Furthermore, the review discusses the commercial outcomes of ongoing clinical trials for various biological-based therapeutic modalities for PsR, providing valuable insights into the evolving landscape of PsR therapeutics. These developments indicate the growing interest and investment in improving treatment options for individuals living with PsR.

Background: Basic helix-loop-helix protein 40 (BHLHE40) can function as both a transcriptional activator and repressor. Recent studies have reported its regulatory functions in T helper (Th)1 and Th17 immune responses. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which joints are involved. Both Th1 and Th17 contribute to the pathogenesis of the disease. In the present study, the levels of BHLHE40, interleukin 17 (IL-17), and interferon-gamma (IFN-γ) were assessed in the RA patients.

Methods: Two groups, including RA patients and healthy individuals, were included in the study. The relative expression levels of BHLHE40, IL-17, and IFN-γ were quantified in peripheral blood mononuclear cells (PBMCs) using real-time PCR.

Results: The results showed that the level of BHLHE40 was significantly higher in RA patients compared to the healthy control (P < 0.001) (11.1-fold increase). Accordingly, a significant increase in the levels of IL-17 (8.1 folds increase) (P < 0.021) and IFN-γ (12.7 folds) (P < 0.001) was observed.

Conclusion: Evaluation of the expression level of BHLHE40 in RA patients showed a significant increase. In line with the elevated level of BHLHE40, a significant increase in the expression level of IL-17 and IFN-γ was also detected. These findings point to the possible role of BHLHE40 in the disease course or severity by elevating the levels of inflammatory cytokines, including IL-17 and IFN-γ. Therefore, BHLHE40 might be considered either as a putative biomarker or as a candidate for therapy in a variety of human diseases.

Background: Toxoplasma gondii (T. gondii) is a widespread apicomplexan parasite that affects approximately one-third of the global population, posing particular risks to pregnant women and individuals with weakened immune systems. Despite its significant impact, there is currently no vaccine available for humans.

Objective: This study employs computational methods (in silico) to investigate the physicochemical, antigenic, and structural properties of Perforin-like proteins (PLPs) from T. gondii, as well as to identify immunogenic epitopes within these antigens.

Methods: For this aim, amino acid sequences of TgPLP1 and TgPLP2 were retrieved and submitted to the ProtParam (physicochemical), VaxiJen v2.0 (antigenicity), NetSurfP-6.0 (2D structure), Robetta (3D structure) web servers, along with the IEDB server to decipher the immunogenic epitopes. Subcellular characteristics such as signal peptide, transmembrane domain, post-translational modifications (PTMs), and cellular localization were also predicted.

Results: Both proteins had a high MW of 125.50 and 92.21, respectively, with an alkaline pI, a 30 hours half-life in mammalian reticulocytes, good thermotolerance (high aliphatic index), and hydrophilicity properties (negative GRAVY). They also showed good antigenicity (0.7021 [PLP1] vs 0.5701 [PLP2]), while they were non-allergenic. Both proteins were extracellular with numerous post-translational modification sites (phosphorylation, glycosylation, and acetylation), and a transmembrane domain was only present in TgPLP1, with no signal peptide in both. Furthermore, numerous immunogenic B- and T-cell epitopes were identified within the TgPLPs sequences, suggesting their potential for inclusion in multi-epitope vaccine designs.

Conclusion: Further studies are needed to confirm these findings and assess the efficacy of the proposed vaccine constructs.

The skin, as the body's largest organ, is crucial for maintaining homeostasis and providing protection, making it susceptible to wounds from various causes. Wound healing is a complex process involving numerous cellular activities. Any interruptions can lead to chronic, non-healing wounds, which present significant challenges in healthcare. Interleukin-24 (IL-24), a cytokine within the IL-10 family, has become recognized for its significant role in wound healing due to its diverse effects on cellular processes. IL-24 can inhibit keratinocyte migration, potentially leading to chronic wounds, and promote endothelial cell migration and angiogenesis, which are vital for tissue repair. This dual role highlights IL-24's intricate involvement in wound healing, as it can hinder and aid different aspects of the process. Research indicates that IL-24 expression increases in response to inflammatory mediators and is involved in various immune responses, emphasizing its regulatory function. Further research on IL-24's mechanisms and interactions is essential for developing new therapeutic strategies to enhance tissue regeneration and treat chronic wounds and skin disorders. A deeper understanding of IL-24's functions could transform wound care, providing new approaches for effectively managing and treating conditions involving impaired healing.

Background: Timolol is a beta-adrenergic blocker that has been shown to be effective in the healing of wounds. Oral mucositis (OM), an acute inflammation of the oral mucosa, is a bothersome side effect of some regimens of chemotherapy in which the oral mucosa becomes ulcerated. The current study aimed to evaluate the prophylactic effects of timolol mouthwash in preventing OM in adult patients receiving chemotherapy compared to the placebo.

Method: This randomized, double-blind trial was conducted on 30 adult patients receiving chemotherapy regimen, including doxorubicin or 5-fluorouracil (5-FU). The patients were randomized in a 1:1 ratio to receive either timolol 0.5% (w/v) (n = 15) or placebo (n = 15) mouthwash 5 ml three times per day. The outcomes of the study were the intensity of OM evaluated by the World Health Organization (WHO) mucositis scale and OM-related pain based on the Visual Analog Scale (VAS) weekly during the seven weeks of the study period.

Results: The results of the study showed that the scores of WHO mucositis scale significantly decreased in the timolol group compared to the control group during the study [week 1: mean (SD), 0.02 (0.41) in the timolol group, and 0.67 (0.48) in the control group; week 7: mean (SD), 0.33 (0.61) in the timolol group, and 0.87 (0.74) in the control group; P-value = 0.049]. Moreover, the mean pain scores significantly decreased in the first, second, and third weeks in the timolol group compared to the control group (P-value < 0.05).

Conclusion: The results of this preliminary clinical trial demonstrated that among the patients receiving doxorubicin or 5-FU chemotherapy regimens, the preventive use of timolol mouthwash significantly diminished the severity of OM compared to the control group during the seven weeks of follow-up. The severity of pain was also significantly lower during the first three weeks of the study; however, the effect size was less than the minimal clinically important difference. Further studies are required to assess both the long-term efficacy and safety of timolol mouthwash in preventing OM.

Introduction: Acute pancreatitis (AP) is a serious inflammatory disease of the pancreas that can lead to significant morbidity and increased mortality. The special role of inflammation and disruption of the hemostatic system in the development of severe forms of the disease is known, however, the relationship between inflammatory and anti-inflammatory cytokines and thromboelastogram parameters has not been sufficiently studied.

Aim: The aim of this study is to assess the prognostic significance of thromboelastogram parameters, interleukin-6, and interleukin-22 levels in assessing the risk for developing severe forms of acute pancreatitis.

Material and methods: Data from 149 patients with acute pancreatitis were included in the analysis. The classification of AP was performed according to the 2012 Revision of the Atlanta Classification. Data including gender, age, lab tests, radiological information, and prognosis were included. The following scales were used to assess severity: SOFA scale and BISAP scale. IL-6 and IL-22 were analyzed at 24 h and 48 h after the onset of symptoms. The collected TEG parameters included K-time, R-value, and Maximum amplitude value at admission. All patients were divided into three groups: mild, moderate-severe, and severe pancreatitis.

Results: Statistically significant differences were found between the groups in the IL-6 level at the first measurement and on day 2 of the study. IL-22 values were also higher in the group with severe pancreatitis, however, on day 2, its level became lower compared to the group of patients with moderate and mild pancreatitis. Statistically significant differences were found in the level of K-time, R-value, Maximum amplitude, fibrinogen concentration, and platelets count, demonstrating a hypercoagulation state in severe pancreatitis at admission. The conducted logistic regression showed that the factors associated with the development of severe forms are the number of points on the BISAP scale, the level of interleukin-6 in the first 24 hours of the disease, delta IL-22, and K-time. (AUC = 0.948).

Conclusion: The study highlights that both IL-6 and IL-22 play crucial roles in the inflammatory cascade of severe acute pancreatitis. Their levels, along with specific hemostasis parameters like K-time and BISAP score, serve as reliable early predictors of disease severity.

Introduction: Anecdotal reports describe patients with concurrent idiopathic inflammatory myopathy (IIM) and celiac disease (CeD) in whom the introduction of a gluten-free diet led to dramatic improvement of myositis. We first systematically reviewed all peer-reviewed publications on concomitant IIM and duodenal biopsy-verified CeD. The collected evidence was suggestive of associations between myositis disease activity and gluten exposure in some patients with IIM-CeD.

Objective/methods: To investigate possible explanations for the observations, an exploratory review of basic pathophysiological relationships between IIM and gluten-related disorders was performed using a combined strategy of systematic and non-systematic literature searches and forward and backward citation tracking.

Results: The investigations revealed close pathophysiological associations between IIM and the autoimmune gluten-related disorders CeD, dermatitis herpetiformis, and gluten ataxia. Common traits include shared genetic predisposition through HLA-DQ2.5/-DQ8, disease activity-associated autoantibodies, histopathological parallels with inflammatory cell infiltrates, and similarly distributed structural homologous transglutaminases (TGs). HLA-DQ2.5-restricted gluten-specific CD4+ T cells of a rare, uniform phenotype are reported in CeD and connective tissue disease. Expanded T-cell clones with identical phenotypes and CDR3β motifs indicate the presence of a continuous, antigen-driven T-cell response.

Conclusion: The investigations revealed that the main components involved in the adaptive immune response in the CeD gut may be present in HLA-DQ2.5+/-DQ8+ IIM muscle. The collected evidence supports the notion that in some genetically predisposed patients with IIM, gluten may act as an exogenous antigen driving myositis. Further Research/Clinical Implications: To test the above hypothesis, clinical trials combined with immunological studies are needed. Meanwhile, the inclusion of HLA-DQ typing may be justified, and subsequent small-intestinal biopsies in HLA-DQ2.5/8+ individuals with IIM.