Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Allergic rhinitis (AR) is a leading public health problem with high prevalence, but the therapies remain limited. Cang Er Zi Powder (CEZP), a Traditional Chinese Medicine formula, has been used for the clinical treatment of chronic rhinitis and allergic rhinitis in China for decades. However, the underlying mechanism is unclear.

Objective: In this study, we aimed to clarify the pharmacological mechanism of CEZP on allergic rhinitis.

Methods: The active ingredients of CEZP were screened in the TCMSP (http://tcmspw.com/tcmsp.php) database. The targets related to "allergic rhinitis" were retrieved from MALACARDS, TTD, and DisGeNET disease target databases. The active ingredients and the candidate targets for AR were constructed and visualized using Cytoscape 3.7.2 software. The underlying mechanism involved in the treatment of CP against AR was analyzed using the WEB- based GEne SeT AnaLysis Toolkit. The effects of CEZP on levels of β-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α on DNP-IgE/HSA-stimulated rat basophilic leukemia cells were determined by enzyme-linked immunosorbent assay (ELISA) kits.

Results: A total of 78 active ingredients in 9 Chinese herbs of CEZP and 90 target overlap targets from CEZP and AR were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the inflammation response and NF-κB signaling pathway were responsible for the therapeutic targets of CEZP on AR, and CEZP could suppress mast cell degranulation via Toll-like receptor (TLR) and NF-κb signaling pathway.

Conclusion: Network pharmacology analysis and in vitro assays suggested that CEZP may exert therapeutic effects on AR by inhibiting the NF-κB signaling pathways.

In recent years, phenolic acids have garnered considerable interest on account of their diverse biological, practical, and pharmacological effects. Chlorogenic Acid (CGA), presently referred to as 3-CQA, is the most prevalent isomer among caffeoylquinic acid isomers (3-, 4-, and 5-CQA). Among the naturally occurring phenolic acid compounds found in green coffee extracts and tea, it is one of the most readily accessible acids. Recent studies have demonstrated that chlorogenic acid exerts its anti-inflammatory effects via various mechanisms, including the inhibition of inflammatory mediators, demonstration of antioxidant activity, modulation of signaling pathways, and regulation of the immune system. Each of these mechanisms is essential for immune system regulation. Chlorogenic acid mitigates tissue injury and impedes the inflammatory response through mechanisms, including inhibition of pro-inflammatory chemical synthesis and activity, scavenging of free radicals, and modulation of immune cell functionality. Throughout this review article, we have methodically examined the advantageous contributions of CGA in relation to its origin, assimilation, metabolism, molecular mechanisms, mechanistic effects, and impact on various forms of inflammation.

Psoriasis, a chronic inflammatory skin disorder affecting approximately 2% of the global population, is characterized by a complex interplay of immunological dysregulation, genetic predisposition, and environmental factors. This review explores the dynamic mechanisms underlying psoriasis, highlighting the role of T lymphocytes in targeting healthy skin cells, leading to inflammation and the formation of characteristic white scaly patches on various body parts. Over the past 15 years, significant strides in unraveling the origins of psoriasis have paved the way for the development of precise and highly effective treatments. Key insights into the pathogenesis, particularly the dominance of interleukin-17 (IL-17) and interleukin-23 (IL-23), have shaped therapeutic strategies to mitigate chronic inflammatory disorders. Notably, various therapies employing different mechanisms of action, including interleukin blockers and tumor necrosis factor-alpha (TNF- α) inhibitors, have emerged as valuable options for psoriasis management. This review provides a comprehensive overview of the current understanding of psoriasis pathophysiology and highlights advanced therapeutic approaches that are widely accessible. The focus extends to emerging targeted drugs, such as netakimab, which functions as an interleukin-17 blocker, currently undergoing clinical trials for psoriasis treatment. By synthesizing the latest research findings, this article aims to contribute to the knowledge base surrounding psoriasis, offering clinicians and researchers valuable insights into the evolving landscape of psoriasis treatment modalities.

The largest and most defensive organ in the human body is the skin. Skin health significantly affects the quality of life due to its crucial function in aesthetic appearance. The onset of numerous skin illnesses is frequently accompanied by chronic skin inflammation. Immune-mediated reactions defend the body against external harm and need to be quickly controlled. If unregulated, they can result in long-term cellular damage and a variety of skin diseases. Dermatological illnesses encompass a wide range of skin conditions, including but not limited to acne, eczema, psoriasis, vitiligo, dermatitis, skin cancer, and fungal infections. Phytochemicals are produced by plants as a defense mechanism against pathogens that have various biological activities and can be harnessed for therapeutic purposes. Through the quenching of free radicals and the suppression of nuclear factor-κB, phytochemicals shield the skin from damage. Phytochemicals also offer a safe topical delivery system for improving the skin and regenerative treatment. Some phytochemicals' direct molecular targets have been identified, and their underlying mechanisms of action are being researched. In this review, we summarise current studies on phytochemicals' impacts on dermal illnesses and their underlying mechanisms of action.

Introduction: Acanthosis Nigricans is a dermatological condition characterized by hyperpigmented velvet plaques that can be observed in flexural areas such as the neck, axilla, and groin. AN is frequently associated with insulin resistance and obesity, however, it can also appear in non-obese people and as a paraneoplastic disease. Its prevalence varies across different populations, with higher rates observed in individuals with obesity, diabetes, and certain genetic syndromes. Classification of AN can be based on underlying etiology, distinguishing primary and secondary forms. Pathogenesis is the complex interplay of genetic, hormonal, and environmental factors, with insulin resistance playing a central role. Diagnosis relies on clinical evaluation of characteristics of skin changes, often requiring further investigation for underlying systemic disease. Topical therapies involve keratolytic agents, retinoids, and alpha hydroxyl acids to improve the cosmesis and reduce the plaque's thickness. Treatment strategies address underlying conditions by emphasizing lifestyle modifications and in some cases, pharmacological interventions.

Objective: This review aims to comprehensively examine the pathogenesis, clinical manifestation, and management of acanthosis nigricans.

Discussion: AN is closely linked to insulin resistance, characterized by impaired cellular response to insulin, leading to compensatory hyperinsulinemia. Recognizing AN's clinical presentation is paramount for early diagnosis and appropriate management.

Conclusion: Acanthosis Nigricans is a skin condition characterized by dark, thickened patches of skin, typically occurring in skin folds and creases. It can be a sign of an underlying health issue such as insulin resistance, obesity, hormonal disorders, or certain medications. Proper diagnosis and management of the underlying conditions are crucial. Treatment may involve addressing the underlying causes, lifestyle changes, and topical medications to improve the appearance of the skin. Regular monitoring and follow-up with a health care professional are essential for optimal management and to prevent complications.

Background: Sepsis is a life-threatening condition responsible for high morbidity and mortality rates around the world and is characterized by a dysregulated host response to infection, resulting in multiple organ dysfunctions. Eugenol is a phenolic aromatic compound derived from clove oil. It has anti-inflammatory, antioxidant, antibacterial, antiviral, antifungal, and anticancer characteristics, which have led to its extensive use in diverse fields, including cosmetology, medicine, and pharmacology. The ongoing study aimed to evaluate the efficacy of eugenol-loaded chitosan nanoparticles (EC-NPs) on sepsis-induced liver damage using the cecal ligation and puncture (CLP) model.

Methods: Thirty male albino rats were randomly divided into five groups: Sham, sepsis, and septic rats treated with chitosan, eugenol, or EC-NPs.

Results: EC-NPs showed excellent antibacterial, antioxidant, and anti-inflammatory effects in vitro. EC-NPs administration significantly improved liver function, as indicated by the decreased liver enzyme activities and C-reactive protein (CRP) level, as well as the increase of albumin content. Moreover, EC-NPs caused an increase in glutathione-reduced and antioxidant enzymes activities, as well as a reduction of malondialdehyde and nitric oxide formation. In addition, the EC-NPs treatment reduced the DNA damage in septic rats; also, the EC-NPs treatment repaired, to some extent, the abnormal architecture of the hepatic tissues of septic rats. Furthermore, the immunohistochemical examination showed a marked decrease in inflammation through the reduction of TNF-α and IL-1β expression.

Conclusion: In conclusion, EC-NPs attenuated liver injury in sepsis through their antiinflammatory, anti-bacterial, anti-oxidant activities and protection of DNA.

Background: Inflammatory bowel diseases (IBD) necessitate cost-effective biomarkers for efficient management. This study aimed to explore the potential correlations of neutrophil-to-- lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) with IBD disease activity. Additionally, we assessed their associations with other inflammatory markers.

Methods: We recruited 180 IBD patients with over 12 months of disease duration, categorized into two groups: Group 1 (active IBD) with 113 cases and Group 2 (inactive IBD) with 67 cases, alongside 200 group-matched healthy controls (Group 3). Hemogram, NLR, LMR, PLR, hs-CRP, ESR, fecal calprotectin (FC), and relevant parameters were recorded.

Results: NLR and PLR were elevated, while LMR was decreased in active IBD patients compared to those in remission. The cutoff values for active IBD were determined as NLR > 1.98, LMR < 3.01, and PLR > 147, exhibiting sensitivity of 92%, 88%, and 91%, and specificity of 93%, 87%, and 89% respectively. Optimal cutoff values for IBD disease activity were CRP > 9.71, ESR > 24, and FC > 176. Multivariate logistic regression identified NLR, LMR, and PLR as robust parameters for discriminating IBD disease activity after adjusting for WBC, CRP, ESR, and FC markers (p < 0.05). NLR and PLR exhibited proportional increases with IBD severity, while LMR lacked such predictive capability.

Conclusion: NLR, PLR, and LMR emerge as simple, non-invasive, and cost-effective independent markers of IBD disease activity, complementing traditional markers like CRP and ESR.

The landscape of wound management has undergone a revolutionary transformation with the integration of nanomaterials-based therapeutics. This abstract explores the profound impact of nanotechnology on wound care, highlighting the unique properties of nanomaterials and their role in advancing therapeutic interventions. Nanomaterials, characterized by their dimensions at the nanoscale, have emerged as versatile tools in wound management. The review focuses on various types of nanomaterials, including nanoparticles, nanofibers, and nanocomposites, which offer tailored solutions for optimizing wound healing processes to facilitate controlled drug delivery, developing a novel approach on account of achieving controlled transport of bioactive agents, such as growth factors, antimicrobial compounds, and anti-inflammatory drugs. This precision in drug delivery enhances therapeutic efficacy, promoting optimal wound healing outcomes. One of the pivotal contributions of nanomaterials to wound management is their engineered antimicrobial properties. Nanoparticles also exhibit effective antibacterial characteristics, addressing concerns related to wound infections. Nanomaterials integrated into dressings and scaffolds enhance mechanical strength and provide a conducive environment for cellular processes, fostering tissue regeneration, angiogenesis, and extracellular matrix synthesis. Nanoparticles with anti-inflammatory and antioxidant functionalities create a balanced microenvironment, reduce chronic inflammation, and promote a pro-regenerative milieu. In conclusion, integrating nanomaterials into wound management strategies represents a paradigm shift in therapeutic approaches.

Background: A neglected zoonosis, Cystic Echinococcosis (CE), is most common in developing nations worldwide. Vaccination is, therefore, helpful in preventing this disease.

Objective: Predicting the main biochemical properties of E. granulosus Calreticulin (CRT) and its possible B-cell and T-cell-binding epitopes as a valuable candidate for immunization was the goal of the current study.

Methods: Predictions were made to determine biochemical, antigenic, structural, and subcellular characteristics, along with the immunogenic epitopes, using several online servers.

Results: The extracellular 48.15 KDa protein exhibited no allergenicity, while possessing hydrophilicity (GRAVY: -0.785), stability (instability: 33.88), tolerance to a wide range of temperatures (aliphatic: 62.45), and 59 post-translational modification sites. The secondary structure mostly comprised random coils and extended strands. The 3D model was generated using the Robetta server (confidence: 0.72), and was rehashed and confirmed subsequently. Common B-cell epitopes were discovered by three servers and screened for antigenic, allergenic, and solubility traits. Moreover, MHC-associated epitopes for mice and humans were predicted in E. granulosus CRT with subsequent screening.

Conclusion: This work offers a foundation for further investigation in order to design an effective vaccination against CE. Further empirical research on the examined protein solely or in combination with other antigens is needed.