Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Introduction: Interleukin-6 (IL-6) is a pleiotropic cytokine produced by several immunologic cells during inflammatory processes, showing an increased serum value in several autoimmune diseases and infections. Recently, it has been used to evaluate lung involvement in COVID-19 infection, and a specific laboratory test has been developed for such a purpose. We used IL-6 to monitor the evolution of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in two patients.

Case summary: We observed two cases of generalized allopurinol-induced adverse cutaneous reactions, including severe hypersensitivity. Serum IL-6 measurement allowed us to evaluate the magnitude of the immune and inflammatory status of patients better than C Reactive Protein (CRP) or White Blood Cell (WBC) count and to evaluate the response to the treatment.

Conclusion: Although different cytokines and serum markers have been proposed for the diagnosis of severe cutaneous adverse reactions (SCAR) like SJS/TEN, they are still experimental. We were the first to use IL-6 measurement as a helpful biomarker in the diagnosis and therapeutic management.

Allergic rhinitis (AR) is a common, chronic inflammatory disorder of the upper respiratory tract, primarily caused by exposure to environmental allergens such as pollen, dust mites, and mold. It has a substantial impact on daily life, often leading to sleep disruption, decreased productivity, and a heightened risk of asthma and other related conditions. The underlying mechanism of AR involves an IgE-mediated immune reaction, with both immediate and delayed inflammatory responses contributing to ongoing symptoms. AR can be classified into several types-seasonal, perennial, occupational, and drug-induced-which aids in its diagnosis and personalized management. Key risk factors include hereditary susceptibility, environmental pollution, and modern lifestyle factors. Diagnosis is typically based on a detailed medical history, skin prick testing, and serum IgE measurements. Treatment strategies involve the use of antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists, complemented by allergen-specific immunotherapy and lifestyle modifications such as allergen avoidance. In recent years, advanced therapies like targeted biologics (e.g., dupilumab) and probiotic-based treatments have emerged, offering promising new avenues for patients with persistent or severe symptoms.

Introduction: Gingivitis is the initial manifestation of periodontal disease, characterized by bacteria and inflammatory mediators, such as IL-32. This study aimed to determine whether the rs45499297 genetic variant of the IL32 gene and its serum and salivary levels are associated with gingivitis. In addition, we investigated whether transcription factors bind differentially in the presence of this genetic variant.

Methods: The study was conducted with 147 subjects. The rs45499297 variant was analyzed using the PCR-RFLP technique, while cytokine levels were measured using the ELISA assay. The affinity of the transcription factors in the presence of the gene variant was analyzed using bioinformatics methods. The results suggest that schooling, salivary flow, lipids, and salivary IL-32 levels were associated with gingivitis. Furthermore, the TC genotype, in the presence of obesity, conferred an increased risk of gingivitis, which was associated with lower serum IL-32 levels. Bioinformatics analysis revealed that the transcriptional factor LRH1 binds with a higher affinity to the C allele than to the T allele of the studied genetic variant.

Results: The findings of this study demonstrate the multifactorial nature of gingivitis, wherein the interplay between genetics and obesity serves as a regulatory factor in inflammation and periodontal risk. The preferential binding of LRH1 to the C allele suggests a molecular link between the genetic variant, inflammatory dysregulation, and the altered metabolic environment in obesity.

Conclusion: Our data show that the rs45499297 gene variant is only associated with gingivitis in the presence of obesity and affects serum cytokine levels. Additionally, we identified the potential involvement of LRH1 in regulating the IL-32 gene expression.

Psoriasis is an immune-mediated skin disease manifested in more than 3% of Americans and over 125 million people worldwide. The inflammatory skin condition with an increased rate of keratinocyte turnover involves every level of the skin and exhibits various forms of the disease, including plaque, guttate, inverse, pustular, and erythrodermic psoriasis, as well as disease-associated conditions, such as psoriatic arthritis and nail psoriasis. Innovative treatment has highlighted the importance of Apremilast, an oral drug that belongs to the phosphodiesterase- 4 (PDE4) class, which was approved by the FDA in 2014. Apremilast works by increasing the presence of cyclic adenosine monophosphate (cAMP) within cells, thereby affecting inflammatory processes and reducing the production of pathological cytokines. Randomized controlled trials have shown that it effectively treats moderately to severely affected plaque psoriasis and psoriatic arthritis, and it is safer than traditional systemic agents. The new perspective on the usage of ethosomes, niosomes, liposomes, and nanostructured lipid carriers in psoriasis treatment is based on emerging nanotechnology in drug delivery systems. These new formulations are designed to enhance the solubility and targeted release of Apremilast, thus providing an enhanced therapeutic effect. This review will discuss the basic mechanisms of the disease known as psoriasis, as well as the mode of operation, pharmacological properties, clinical trials, and pharmacokinetics of apremilast, particularly in relation to nanocarrier modification of this promising drug.

Vanillin is a naturally occurring compound found in numerous plant species and is commonly utilized in food, beverages, cosmetics, and pharmaceuticals. It is the main ingredient in vanilla pods, and numerous studies have indicated that it has a variety of pharmacological properties, including anti-inflammatory, antioxidant, and anticancer properties. Vanillin is extensively utilized in modern drug research for the treatment of many diseases, including cancer, due to its anti-inflammatory properties. Besides its application in food and flavoring, vanillin acts as a precursor in the production of other valuable petroleum-derived chemicals. This review provides a thorough explanation of the impact of this phytochemical on many signalling pathways, which are interconnected with the root cause of disease. This review also discusses its pharmacokinetic characteristics and clinical trial studies.

Introduction: Cognitive impairment linked to neurodegenerative diseases poses a considerable challenge, requiring the exploration of plant-derived therapeutic alternatives. Ruellia tuberosa, a medicinal plant recognized for its anti-oxidant and anti-inflammatory properties, was examined for its therapeutic potential in a rodent model of memory impairment.

Method: The present study aimed to evaluate the effects of Ruellia tuberosa ethanolic extract (RTEE) on aluminium chloride (AlCl3)-induced Alzheimer's disease (AD) in adult Wistar rats. In-vitro cell line study showed decreased formation of reactive oxygen species (ROS), decreased levels of IL-6 (Interleukin-6), and suppressed NF-κB (Nuclear factor kappa-B) translocation, which further confirmed RTEE's antioxidant and anti-inflammatory characteristics. Following the objective, thirty adult Wistar rats were taken and divided into five groups (n=6). They were treated with Normal saline, AlCl3 (100 mg/kg), DPZ (Donepezil- 3 mg/kg), and RTEE (100 and 200 mg/kg), respectively, for 35 days.

Results: Various behavioral and biochemical parameters, along with the oxidative and inflammatory biomarkers, were assessed to determine the effects of RTEE. The plant extract at both the doses (100 and 200 mg/kg) demonstrated increased body weight, improved motor coordination as demonstrated by an increase in fall-off time on the Rota rod apparatus, decreased escape latency in the Morris water maze test, reduced transfer latency (TL) in the elevated plus maze test, increased time spent in the target quadrant, and increased exploration time in the novel object recognition test. Furthermore, RTEE treatment exhibited decreased levels of malondialdehyde (MDA) and acetylcholinesterase (AChE) activity and increased levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total protein. Additionally, RTEE reduced levels of inflammatory cytokines, such as TNF-α and IL-1β, which decreased neuroinflammation and amyloid-beta levels. Additionally, the extract exhibited cholinergic system modulation, as observed by improved acetylcholinesterase activity, suggesting its potential role in neurotransmitter regulation. Histopathological study further confirmed its neuroprotective potential by reducing neuronal degeneration in brain regions (hippocampus and cortex).

Conclusion: According to the study's findings, memory impairment in the AlCl3-induced rat model of AD was ameliorated by both doses of RTEE. However, further studies need to be conducted to establish its therapeutic effects in neurodegenerative diseases.

Introduction/objective: Alzheimer's disease is a neurodegenerative disorder characterized by progressive cognitive decline and memory loss. In recent years, inflammation has gained recognition as a key contributor to both the onset and progression of Alzheimer's disease, acting through complex pathways that include neuroinflammation and immune system dysregulation. This study aims to systematically review the relationship between Alzheimer's disease and inflammation, focusing on publication trends from 2000 to 2023.

Methods: Using the Scopus database, a bibliometric analysis was conducted through Microsoft Excel, Harzing's Publish or Perish, and VOSviewer, examining publication trends, citation metrics, and co-network visualization.

Results: A total of 1,205 relevant publications were identified, revealing a steady increase in research output. The majority of contributions came from the United States (33.1%), China (16.8%), and the United Kingdom (8.8%). Key terms such as "neuroinflammation", "cytokine", "microglia", "amyloid beta", and "oxidative stress" dominated the literature, while emerging keywords included "neuroprotection", "BDNF", "inflammasome", and "mitochondria".

Conclusion: These findings underscore the growing focus on the role of inflammatory processes in the etiopathology of Alzheimer's disease, as well as efforts to identify biomarkers and neuroprotective therapeutic targets. This study provides a detailed mapping of the research landscape, offering insights into the evolving knowledge structure and highlighting prominent countries, institutions, authors, journals, and highly cited articles. By identifying key trends, this review advances our understanding of the interplay between inflammation and Alzheimer's disease, paving the way for future research and clinical strategies.

Background: Lymphocytic Esophagitis (LyE) and Eosinophilic Esophagitis (EoE) share many clinical and endoscopic features. However, their treatment outcomes and prognoses differ significantly. LyE, the least recognized form of esophagitis, requires further research. This study compares symptoms, risk factors, and endoscopic findings in LyE and EoE patients.

Methods: This study reviewed medical records, esophagogastroduodenoscopy (EGD) findings, and biopsy data. Patients aged 18 years and older who underwent EGD-guided segmental esophageal biopsies between March 2018 and January 2024 were included. Demographic data, clinical features, risk factors, and EGD findings were compared between LyE, EoE, non-specific esophagitis (NSE), and normal esophageal histology (NEH) groups. The NSE and NEH groups served as controls.

Results: The cohort included 11 LyE cases (1.25%), 79 EoE cases (8.96%), 447 NSE cases (50.68%), and 345 NEH cases (3.11%). LyE patients were older, with a mean age of 54.81 years, and 72.72% of them were female. In contrast, EoE patients were younger, with a mean age of 43.52 years, and had a male predominance. Cases of dysphagia, dyspepsia, and nausea or vomiting occurred in both groups. Food impaction was more frequent in EoE. Smoking, alcohol use, and autoimmune diseases (e.g., hypothyroidism and rheumatoid arthritis) were significant risk factors for LyE. Atopic conditions such as asthma and allergies were linked to EoE. Endoscopic findings often overlapped in LyE and EoE. Esophagitis and strictures were more common in LyE, while rings and furrows were more frequent in EoE. All endoscopic findings, including normal mucosa, were significant in LyE and EoE compared to controls. However, rings, linear furrows, and exudates were not significant when comparing LyE to controls.

Conclusion: LyE is a rare form of esophagitis with clinical and endoscopic features similar to EoE. Accurate histopathological diagnosis is essential for differentiation. LyE is more common in older females with autoimmune conditions, while EoE affects younger males with atopic conditions.

Objectives: To find out how arthritic diseases affect the pharmacokinetics of prednisolone, diclofenac, and methotrexate when given individually and as a cassette in male Sprague- Dawley rats, the study's main goal was to look into drug-drug interactions (DDI). For the treatment of moderate to severe arthritis, doctors commonly prescribe all three drugs alone or in combination.

Methodology: Pharmacokinetics (PK) was evaluated using individual and cassette dosing in male Sprague-Dawley rats in a fasting state. Respective experimental groups were administered orally with prednisolone (5.0 mg/kg), diclofenac (10.0 mg/kg), and methotrexate (0.5 mg/kg) during either discrete or cassette dosing, at a dose volume of 5 mL/kg. Blood samples were collected through the jugular vein and analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetics parameters were calculated using Phoenix software version 8.1.

Results: Prednisolone significantly decreased the AUC0-last in both the arthritic group and the cassette group when compared to the standalone normal animal group. Neither cassette dosing in the normal group nor discrete dosing in the arthritic group affected the pharmacokinetics (PK) of diclofenac. However, the AUC0-last value for diclofenac significantly decreased during cassette dosing in the arthritic group. Individual administration of methotrexate in the arthritic group resulted in a significant decrease in AUC0-last, while the healthy group experienced a substantial increase when administered as a cassette.

Conclusion: Along with the pharmacological DDI, this study looked at how disease affected the PK of prednisolone, diclofenac, and methotrexate when these drugs were given in both discrete and cassette doses. Significant differences in AUC0-t and Cmax of prednisolone and methotrexate pharmacokinetics when dozed as a cassette or individually in arthritic groups were noticed. The serum concentration of methotrexate increased when it was combined with diclofenac. Further, the metabolism of methotrexate increased when combined with prednisolone.