Recent Advances in Inflammation & Allergy Drug Discovery最新文献

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.

Introduction: Phosphodiesterase 7 (PDE7) is a key enzyme in the PDE superfamily responsible for degrading cyclic adenosine monophosphate (cAMP) in pro-inflammatory and immunomodulatory cells. Elevated PDE7 activity is associated with inflammatory processes and various diseases. Suppression of PDE7 raises cAMP levels, reducing mucous secretion, cellular inflammation, and airway obstruction.

Objective: This review provides an overview of the role of PDE7 in inflammatory disorders and highlights recent advances in the development of selective PDE7 inhibitors for therapeutic applications.

Methods: The review consolidates findings on the structure-activity relationships of PDE7 inhibitors. Key structural classes of small molecule inhibitors, including quinazolinone derivatives, thiadiazines, pyrimidines, and others, are discussed alongside preclinical and clinical data on selective inhibitors such as BRL50481 and OMS527.

Results: Selective PDE7 inhibitors have shown exposed potential in animal models to reduce cAMP degradation, leading to decreased inflammation and airway obstruction. BRL50481 remains the only commercially available selective PDE7 inhibitor, while OMS527 has progressed to clinical trials, demonstrating promise in treating inflammatory, neurological disorders, and leukemias.

Conclusion: Selective PDE7 inhibitors represent a novel therapeutic class for inflammatory and neurodegenerative diseases. Further research is characterised by immune dysregulation.

Micro(nano)plastics (MNPs) have become pervasive environmental pollutants due to widespread use and inadequate waste management practices. These tiny particles infiltrate various ecosystems, including the human body, raising significant concerns about their potential health effects. Of particular concern is their impact on human reproductive health, with emerging research indicating MNPs' ability to breach biological barriers, accumulate in reproductive organs, and potentially reach the placenta. A comprehensive literature search spanning from July 2015 to July 2024 was conducted across prominent electronic databases, including Pub- Med, Scopus, Web of Science, and Google Scholar. Key search terms such as "micro and nanoplastics," "microplastics and male reproductive health," "microplastics and female reproductive health," "transgenerational spread of microplastics," and "microplastics and fetal health" were used to identify relevant studies published in peer-reviewed journals, books, and reputable conference proceedings. Selection criteria favoured review articles, original research papers, metaanalyses, and authoritative texts published in English. Synthesized findings from these studies were critically analysed to underscore their potential impacts on reproductive health. The accumulating evidence emphasizes the urgent need for further research to fully grasp the risks posed by MNPs to human reproductive health. Effective mitigation strategies are essential to minimize exposure and mitigate potential long-term consequences. Policy interventions aimed at enhancing waste management practices and regulating plastic usage are crucial to curb the environmental spread of MNPs and safeguard human reproductive health effectively.

Psoriasis is a relapsing, chronic, and inflammatory disease of the skin. However, its impact goes beyond just pathophysiology and takes a toll on the physical and psychological aspects of the health of the afflicted, lowering the quality of life significantly. It is also a mechanistically complex disease with a substantial immune component. Therefore, ongoing treatment strategies focus on targeting at least one immune component associated with the disease development and progression by employing biological agents like IL-1 inhibitors, IL-23 inhibitors, IL-36 inhibitors, and TNF-α inhibitors. Psoriasis-induced disruptions in cellular signalling pathways have drawn significant attention as novel drug targets. Numerous novel synthetic agents, such as JAK/STAT inhibitors [ruxolitinib, peficitinib], TYK2 inhibitors [zasocitinib, ropsacitinib], RORꝩT inhibitors [cedirogant], A3AR agonists [piclodenoson], and CXCR2 antagonists [vimnerixin] are undergoing extensive clinical trials and have demonstrated beneficial outcomes in multiple phases of these trials. Deucravacitinib, an orally administered TYK2 inhibitor, has recently received FDA approval for the treatment of moderate to severe plaque psoriasis. These synthetic agents hold promise to change the outlook of psoriasis management by modulating specific molecular targets associated with the dysregulated immune response observed in psoriasis. Moreover, these pathways can be exploited to personalize anti-psoriatic therapy, minimize side effects, and maximize therapeutic outcomes. Altogether, the integration of biological agents and synthetic agents can overcome the challenges associated with the management of the repertoire of psoriatic pathophysiology and symptoms.

Introduction: Acute Respiratory Distress Syndrome (ARDS) is the pathophysiologic state of the inflammatory response to lung injury characterized by alveolar epithelial cell damage and increased cytokine production and accumulation in the lungs.

Objectives: The current study was performed to identify the molecular mechanisms of ARDS related to the proteins elevated in the lung (PEL) and NF-κB pathway regulatory genes (GRNF). In addition, the phytocompounds were screened to inhibit the representative target genes and proteins associated with ARDS.

Materials and methods: We implemented STRING v11.5 and Network Analyst 3.0 to construct the protein-protein interactions (PPI) network. CytoScape v3.8.2 and DisGeNet v7.3.0 were utilized to visualize and identify genes involved in respiratory diseases. The Cytohubba module was utilized to identify the hub genes from the constructed PPI network. Autodock Vina and Discovery Studio Visualizer v19.1.0.1828 were utilized for the molecular docking analysis.

Results: The PPI network was constructed with the GRNF genes. Fifty-four genes are identified as biomarkers involved in respiratory diseases (BMRD). About 191 PEL were identified from the human protein atlas database and constructed the PPI network. The interactions between the PPI network of BMRD and PEL were analyzed. The top 100 hub genes and the signaling genes were identified. Based on the identified signaling genes through the PPI network of BMRD and PEL, the metabolic pathway was elucidated, which causes ARDS via NF-κB activation. The ARDS targets (ACVRL1, IKKβ, ITGAL, ITGB2, TGFβR1, and TGFβR2) were selected for the molecular docking study. One hundred and thirty-five chemical compounds from Allium sativum, Alstonia scholaris, Ammi visnaga, Artemisia vulgaris Linn., Houttuynia cordata, and Ocimum gratissimum Linn. were retrieved and used for docking against selected ARDS targets. Among them, genkdaphine from A. sativum inhibited ACVRL1 (binding affinity of -9.2 kcal/mol, and RMSD of 2.607Å), ITGAL (binding affinity of -9.1 kcal/mol, and RMSD of 1.69Å), ITGB2 (binding affinity of -7.9 kcal/mol, and RMSD of 2.184Å), TGFβRI (binding affinity of -8.5 kcal/mol, and RMSD of 1.807Å), and TGFβRII (binding affinity of -8.2 kcal/mol, and RMSD of 1.647Å). Edulisin III from A. visnaga inhibited the IKKβ (binding affinity of -7.4 kcal/mol, and RMSD of 2.223Å).

Conclusion: Genkdaphine and edulisin III may be the therapeutics for treating ARDS. However, further studies are needed to warrant the benefits of genkdaphine and edulisin III in treating ARDS. The study's findings may aid in developing new therapeutic approaches to improve the health status of ARDS-affected patients.

The physiological process of wound healing is complicated and involves extensive connections between biological, molecular, and cellular pathways. Acute and chronic wounds pose a serious socioeconomic burden by impacting millions of people each year globally, which has significantly increased the problem of amputations, longer hospital stays, and mortality. Despite tremendous progress, in aging populations, associated conditions like diabetes and growing antibiotic resistance make chronic wounds even more clinically challenging. Recent developments in science and technology and research at cellular and molecular levels have opened up new possibilities for wound healing by laying the foundation for new technologies, techniques, and information. This review provides an in-depth knowledge of phases of wound healing, innovative methods, and combining technology for wound repair for successful therapies. This study reveals the associated challenges with wound healing dressings, including traditional, advanced, and biotechnology-based dressings. Moreover, this study also includes herbal remedies for wound repair, wound assessment techniques, and experimental wound healing models. This report additionally includes new treatment technologies, such as smart wound dressings capable of real-time monitoring and delivery of drugs at a controlled rate. Finally, an extremely inventive and futuristic approach that adds a new horizon in wound healing is the use of nanobots, and new analytical tools based on machine learning and artificial intelligence (AI) are also considered.

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.