Recent Advances in Inflammation & Allergy Drug Discovery最新文献

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.

Materials 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.

Background: The Coronavirus disease 2019 (COVID-19) pandemic, prompted by SARS-CoV-2, has created complicated health crises. An excessive inflammatory response and cytokine storm characterize severe COVID-19. Corticosteroids like dexamethasone and methylprednisolone are used for their anti-inflammatory effects, but comparisons of their efficacy are lacking.

Objective: This study seeks to rigorously assess and contrast the effectiveness of dexamethasone and methylprednisolone in combating COVID-19 infections.

Methods: This retrospective clinical study evaluates the effects of these two corticosteroids by reviewing the files of 500 hospitalized COVID-19 patients. The baseline characteristics of the patients, chest CT severity score, type of steroid prescription, duration of hospitalization and steroid prescription, dosage of corticosteroid therapy, their recovery status, hospital mortality, and specific disease severity-associated markers, such as lactate dehydrogenase (LDH), complete blood count (CBC), C-reactive protein (CRP), and Erythrocyte sedimentation rate (ESR) were collected and compared.

Results: The study found no significant difference in most disease severity-associated markers between the two corticosteroid groups. However, lower mortality rates and shortened hospital stays were significantly associated with dexamethasone, especially in critical patient groups. A detailed analysis of inflammatory markers suggested minimal differences based on the type of corticosteroid used.

Conclusion: The study indicates that dexamethasone may have some advantages in specific clinical outcomes. Further research needs to explore the mechanisms involved despite similar anti-inflammatory profiles.

The study aims to investigate and assess the effectiveness of current novel techniques for the preparation of an efficient nanocarrier system in resolving the drawbacks associated with the delivery of herbal bioactives to treat rheumatoid arthritis. Systematic utilization of various search engines like Science Direct, Pubmed, Shodhganga, Google Scholar, and Google Patent databases based on various sets of key phrases has been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. The current study summarizes the existing research and development of new nano-formulations with a focus on herbal bioactive compounds for treating rheumatoid arthritis. Physicochemical properties of phytoconstituents, such as low aqueous solubility, low permeation coefficient, and chemical instability, poor bioavailability, short plasma half-life, and ultimately sub-therapeutic efficacy, limit their clinical translation despite their great potency. The utilization of Phytochemical-Based Nanocarrier Approaches for rheumatoid arthritis can be a milestone as a major population is affected by this disease worldwide. The intensive study recapitulates that novel drug delivery systems can provide new opportunities to efficiently deliver herbal bioactives with improved pharmacokinetic and pharmacodynamic properties. The exhaustive study concluded that transferosomes, ethosomes, transethosomes, niosomes, phytosomes, Solid Lipid Nanoparticles (SLN), Nano Lipid Carriers (NLC), bilosomes and hylurosomes are some of the efficient nanocarrier systems that may impart numerous benefits to the delivery of herbal bioactives for treatment of RA. These nanocarrier systems fabricated with phytoconstituents flaunt the evident promising benefits of improved aqueous solubility, low first-pass metabolism with upgraded bioavailability, sustained release action, resistance to enzymatic degradation etc., providing support in rheumatoid arthritis recovery. This review discusses that the upgradation of the pharmacological action and other relevant issues of herbal bioactives are possible by utilizing novel drug delivery systems, resulting in successful development of nano-loaded herbal bioactives. It also focuses on highlighting the pioneering progression in the field of herbal bioactives-loaded nanocarrier systems for rheumatoid arthritis both in vitro and in vivo along with their advanced preparation methods and applications and discussing the opportunities for further prospects. This compiled informative review will enlighten various researchers in the field of delivering herbal bioactives for rheumatoid arthritis.

Cyclooxygenases are enzymes involved in prostaglandin synthesis, a part of the inflammatory process. The most frequently applied anti-inflammatory drugs are NSAIDs; however, these medications exhibit very serious side effects, and often, reduce production or are withdrawn from the market. Recently, researchers were focused on finding new, safe, selective COX-2 inhibitors with safety features. This paper reviews cyclooxygenase enzyme malfunction-related diseases, current therapies and new drug discovery opportunities. Prostaglandin-endoperoxide synthases are enzymes involved in the synthesis of prostanoid peptides through the oxidation of nitric oxide and pyruvate phosphate. They are participating factors for various physiological and pathological processes, which include disorders of the oral tissues such as periodontitis, pulpitis, and oral cancer. This paper is a review of some pharmaceutical products in terms of history, efficiency, and possible side effects as inhibitors of the Cyclooxygenase enzyme. The analysis concludes that more recent Cox inhibitors, such as dietary modifications and natural supplements, hold promise for safer and more efficient treatment of diseases involving Cox enzyme function.

Diabetes is known as one of the most important widespread diseases in the world. Diabetic ulcer is one of the main complications associated with this disease. The use of the capabilities of modern science such as nanotechnology can be effective in developing new strategies for treating diabetic ulcers. Regulating homeostasis, controlling infections, and the ability to regenerate/ heal are some of the proposed mechanisms of nanomaterials in wound healing. In this regard, cuprorivaite bioceramic, as a bioceramic containing copper nanoparticles with effects on angiogenic factors and infection control, can effectively be used in the healing of diabetic ulcers. In this prospective article, we have presented the potential of this bioceramic in the design of new dressings for diabetic wound healing.

Tiliroside, a natural polyphenolic compound found in several plant sources, has garnered attention for its potential to mitigate inflammation and its associated diseases. The current review explores the multifaceted functions of Tiliroside in inflammation-related diseases, delving into the underlying mechanisms and prospects for therapeutic applications. Tiliroside exerts its anti-inflammatory effects through a variety of mechanisms, such as the inhibition of inflammatory mediators' cytokines and chemokines, as well as the suppression of nuclear factor-kappa B (NF-κB) signaling pathways. Additionally, it demonstrates potent antioxidant properties, which further contribute to its anti-inflammatory activity by reducing oxidative stress. In preclinical studies, Tiliroside has shown promising results in ameliorating inflammation in conditions like rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. Furthermore, Tiliroside's ability to modulate immune responses and stimulate tissue regeneration contributes to its potential as a multimodal agent in treating inflammation-associated disorders. In conclusion, Tiliroside emerges as a promising natural compound with a multifaceted role in inflammation-related diseases with understanding the underlying mechanisms of its therapeutic prospects may pave the way for novel treatments.

Background: The orofacial mucous membrane is an appealing route for drug delivery to improve both systemic and local treatments. The aim of the present study was to develop an oral dental film loaded with curcumin hydrotropic solid dispersion for sustained drug delivery in the orofacial region. Compared to other dosage forms, films are the most elegant, palatable, and suitable systems for systemic mucosal drug delivery.

Methods: A hydrotropic solid dispersion technique utilizing 2 M sodium salicylate was developed to enhance the solubility of curcumin, addressing its poor water solubility. By forming a solid dispersion with a 1:4 ratio through solvent evaporation, the in-vitro physicochemical properties of the curcumin-loaded system were evaluated.

Results: The utilization of sodium salicylate hydrotrope in a molecular dispersion significantly improved the solubility and bioavailability of curcumin. Subsequently, an oral dental film loaded with hydrotropic solid dispersion was developed using the solvent casting method with HPMC and gelatin as mucoadhesive polymers. Six different films were prepared using polymeric blends with HPMC and gelatin, which showed homogeneity, yellowish colour, and high drug content uniformity of 98.56 ± 3.24, with thickness ranging from 0.16 mm to 0.24 mm. The films exhibited excellent folding endurance and tensile strength for improved patient palatability. In-vitro studies demonstrated a significant enhancement in curcumin release, reaching a maximum of 94.66% over seven days in the presence of sodium salicylate hydrotrope, following firstorder kinetics. An ex vivo permeation of Cur-F3 film had a significant effect on mucoadhesion.

Conclusion: Using hydrotropes in oral film formulation is a new and sustainable method for delivering clinically significant curcumin through the oral mucosa. As a result, it is recommended for use in the design of treatments for other dental diseases.

Aim: To analyze a broad spectrum of cytokine in the serum of patients with JDM.

Background: Juvenile dermatomyositis (JDM) is the most common subtype of idiopathic inflammatory myopathies characterized by muscle and skin involvement. The etiology of JDM is unclear. A variety of cytokines play a role in the pathogenesis of JDM. Interferons, galectin-9, CLCX10, and neopterin are the most promising biomarkers.

Objective: This study describes the associations between clinical symptoms, cytokine, and interferon profiles in children with JDM.

Materials and methods: Ten patients (6 girls and 4 boys) with JDM were included in the study. The clinical symptoms, disease activity (CMAS, CAT), laboratory parameters, and treatment were assessed. Forty-one cytokines levels and IFN-I scores in the serum were measured. The levels of cytokines were compared with a group of healthy controls (n=25).

Results: Significant differences were observed in 21 of 41 analyzed cytokines between JDM patients and healthy controls. Patients with active disease (n=8) have higher levels of fractalkine (p = 0.036), IFNa (p = 0.037), IFNg (p = 0.037), GRO (p = 0.037), IL-10 (p = 0.037), IL-12p40 (p = 0.037), IL-12p70 (p = 0.048), IL-17a (p = 0.048), IL-1RA (p = 0.037), IL-1a (p = 0.037), compared to patients with inactive disease (n=2). A strong positive association was found between aCAT activity and eotaxin (r=0.753, p =0.012), GRO (r=0.735, p =0.015), IP-10 (r=0.805, p =0.005), and MCP-1 (r=0.734, p =0.016). A strong negative correlation association was observed between CMAS and eotaxin (r= -0.714, p =0.020), GRO (r= -0.727, p =0.017), IL-10 (r= -0.786, p =0.007), IP-10 (r= - 0.719, p =0.019), and MCP-1 (r= -0.800, p =0.005). IFN-I scores showed a positive correlation with IFNa (r=0.790, p =0.007), GRO (r=0.736, p =0.015) and IL-1RA (r=0.930, p <0.001).

Conclusion: Among the spectrum of 41 cytokines, GRO, eotaxin, IP-10, and MCP-1 have shown the strongest association with JDM activity.