Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Objectives: This study aimed to characterize oral and gut microbiota of children with high dmft index and caries-free children at phylum, family and species levels as well as to evaluate the effect of Streptococcus salivarius M18 DSM 14685 (Carioblis) administration on microbiota composition of caries active children.

Materials and methods: Ten children with active caries and nine caries-free children have been recruited. Four samples from different oral niches and stools were collected from each patient for the NGS sequencing of 16s Microbiota rDNA by S5 Ion Torrent.

Results: Our results revealed modifications in the microbiota composition of teeth, saliva and vestibular regions of the oral cavity and faecal samples in the presence of dental caries. These changes were evident at the family and species levels, with no significant differences found at the phylum composition level. In particular, Streptococcaceae were positively correlated to the high degree of caries in all niches, and the analysis at the species level led to the identification of 39 bacterial species significantly modulated in the analyzed groups. The use of probiotic seemed to exert beneficial effects on oral but not on faeces dysbiosis. The intestinal tract was confirmed to have a different microbiota composition compared to the oral cavity.

Conclusion: Dental caries mainly lead to modifications in the oral microbiota composition. Streptococcus salivarius M18 DSM 14685 administration determines a shift in the oral microbiota composition towards a healthier state. Concerning the gastrointestinal tract, our study found for the first time that caries cause the increase of two bacterial species, related to other disorders: Bifidobacterium adolescentis and Ruminococcus torques.

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.

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.

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.

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: Osteoarthritis (OA) stands as the most widespread form of arthritis, representing a primary source of pain and functional impairment among the elderly. It is often referred to as a degenerative joint disease. OA is more than just wear and tear; it is an aberrant remodelling of joint tissues prompted by a deluge of inflammatory mediators released within the compromised joint. This disease affects 15 million people in India annually.

Objective: Aceclofenac is a COX-2 inhibitor that has anti-inflammatory activity. However, aceclofenac has a short mean plasma elimination half-life and poor water solubility. It requires frequent dosing, which has been linked to a number of negative side effects, including bleeding and gastrointestinal irritation. A potential solution to this problem is the transdermal administration of aceclofenac using microsponges. In order to have a synergistic effect along with the bioenhancer effects, piperine was incorporated into the formulation.

Methods: Microsponges were created using the quasi-emulsion solvent diffusion method. After characterization, the prepared microsponges were incorporated into the Carbopol gel. The in vivo study focused on evaluating the optimized formulation, F1.

Results: All the prepared microsponge formulations underwent assessment based on parameters including yield of production, entrapment efficiency, and in vitro drug release. The outcomes indicated that batches ranging from F1 to F9 showed positive entrapment efficiency and in vitro drug release. From 50.37% to 80.76 % and 71.18% to 91.8% and in vivo studies the results reveal that the inflammatory cells in the best formulation Ace(B) group were reduced hence the formulation's anti-inflammatory impact was achieved.

Conclusion: The findings indicate that Formulation F1 exhibits superior entrapment and enhanced drug release. The kinetics study suggests that the optimized formulation aligns well with the Higuchi model and adheres to the Fickian transport drug release mechanism. Animal study findings suggest that optimized formulation Ace(B) may possess ideal -anti-osteoarthritic activity for osteoarthritic disease. Further clinical trials on humans may be conducted in order to make the research fruitful for society.