Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Inflammation plays a significant role in the pathophysiology of Acute Coronary Syndrome (ACS) but is not included in current risk stratification.

Objective: To determine the association between Thrombolysis in Myocardial Infarction (TIMI) risk score and inflammatory biomarkers in the ACS, including unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). We hypothesized that including inflammatory biomarkers could add prognostic value to the TIMI risk score.

Methods: In this cross-sectional study, serum levels of interleukins (IL)-6 and IL-1β and MDA (malondialdehyde) were quantified by ELISA and colorimetry, respectively , patients with ACS (n = 48; 31.3% with UA, 33.3% with NSTEMI, and 35.4% with STEMI) and healthy controls (n = 43). We assessed the TIMI scores in the first 24 h after symptom onset.

Results: The results showed that patients with ACS had significantly higher levels (p<0.05) of the inflammatory biomarkers IL-6, IL-1β, and MDA compared to the control group. However, we found no significant differences in IL-6, IL-1β, and MDA levels among the patients with ACS according to their classification as UA, NSTEMI, and STEMI. Positive correlations were observed between TIMI and IL-6 (r=0.68), IL-1β (r= 0.53), and MDA (r=0.58) in patients with UA and between TIMI and IL-1β (r= 0.62) in STEMI patients.

Conclusion: These data suggest the presence of a pro-inflammatory profile in patients with ACS as well as positive correlations between TIMI scores and the inflammatory biomarkers IL-6, IL-1β, and MDA in patients with UA and between TIMI scores and IL-1β in patients with STEMI. Combining inflammatory biomarkers with the TIMI risk score could provide better insight into the processes involved in ACS.

Purpose: To prepare solid lipid nanopaticles (SLNs) of Ketoprofen (KP) using microwave method. Ketoprofen (KP) is 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic property. The drug has short half-life of 120 mins. It belongs to BCS Class II drug. Gastric irritation is a major limitation for delivery because of acidic nature of the drug. Development of solid lipid nanoparticles with its transdermal drug delivery was the aim of present work.

Methods: Microwave-assisted microemulsion technique was used for the development of solid lipid nanoparticles. Stearic acid was used as lipid and tween 80 was used as surfactant. By varying the type of lipid and input energy watt, batches were formulated. SLNs were evaluated for zeta potential, drug entrapment, particle size and in-vitro drug release. Crystallinity behaviour was determined by differential scanning calorimetry and powder X-ray diffraction. Anti-inflammatory activity was evaluated for batch M4 of SLNs. The gel was prepared for M4 batch. It was evaluated for viscosity, pH, drug content, in-vitro and ex-vivo diffusion study.

Results: SLN were developed successfully. Based on the size, entrapment efficiency, stability and drug release, batch M4 was selected. SLNs showed 74.8% entrapment efficiency. Forty-fold improvement was observed in the solubility. The particle size was of 682.9 nm and average size of 1047 nm. PDI was 0.685. Zeta potential was -29.5 mV. M4 SLNs batch of gel showed burst release followed by a controlled release for 8 hrs in in-vitro drug release.

Conclusion: SLNs were successfully prepared by Microwave-assisted microemulsion technique. SLNs with anti-inflammatory activity was successfully developed with its transdermal delivery.

Background: The organism's defense against aggressive agents is performed by the innate immune system, via activation of pattern-recognition receptors (PRRs). Initially, these agents are recognized by the immune system, resulting in the inflammatory response that activates the pathogen elimination and tissue repair. Inflammasomes are macromolecules related to the host's response to endo or exogenous aggressive agents. Thus, inflammation mediated by inflammasomes plays an important role in the pathogenesis of diseases, such as neurodegenerative disorders, autoimmune diseases, and type 2 diabetes, justifying their attractiveness as drug targets. One of the most important tasks remains in the ATPase nucleotide-binding oligomerization domain nucleotide-binding domain leucine-rich repeat-containing receptors protein 3 (NLRP3), in which the blocking of its oligomerization is related to the functional inhibition of inflammasomes. Here, we performed molecular docking and dynamics simulations for NP3-146, an analog of MCC950, and to obtain information about the complex stability and main interactions with amino acid residues from NLRP3.

Methods: Using the crystalized structure recently deposited in the protein data bank (7alv), molecular docking in GOLD software and Molecular dynamics simulations in GROMACS software were performed, to generate the RMSD, RMSF, Rg, SASA, and H-bond plots.

Results: The results of RMSD, RMSF, Rg, SASA, and H-bond plots of both complexes confirmed the stability at the active site. Besides, the analyses of the most stable conformation showed that the main interactions are performed with Ala227, Ala228, Pro352, Ile411, Phe575, and Arg578 residues.

Conclusion: This report confirmed the stability of NP3-146, similar to the know inhibitor MCC950, and provides various information useful to design NLRP3 inhibitors.

Background: Inflammation is the response to the reaction of any type of bodily injury by elevating cellular metabolism and releasing soluble mediators. It is also a contributing factor of pain. Predimenol, which has previously been known as DLBS1442, is a bioactive extract from Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae). It can be an alternative treatment for pain relief, especially for long-term use.

Objective: The objective of this study is to evaluate the anti-inflammatory activities of predimenol through the evaluation of several parameters involved in the inflammatory pathway.

Methods: Cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-  (TNF-), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), and nuclear factor B (NF-B) were observed after 24 h exposure of predimenol (0-180 µg/mL) to lipopolysaccharides (LPS)-activated RAW 264.7 cell. The inflammatory markers were measured using nitric oxide (NO) assay and enzyme-linked immunosorbent assay (ELISA) for COX-2 inhibitor assay. The gene expressions of TNF-α, IL-1β, IL-2 and IL-6 were quantified using the polymerase chain reaction (PCR) method. Western blotting was applied to detect phosphorylated IB kinase (IKK) protein to confirm the activation of NF-κB.

Results: Our study showed a similar mechanism with most non-steroidal anti-inflammatory drugs (NSAIDs). Predimenol consistently downregulated the expression of iNOS and inhibited COX-2 activity. Moreover, predimenol significantly inhibited the LPS-induced production of NO, TNF-α, IL-1β, IL-2 and IL-6. Down-regulation of these markers was suggested due to the reduction of NF-κB transcription level and activation by predimenol.

Conclusion: Predimenol exhibits anti-inflammatory activities through NF-kB inactivation-mediated COX-2 suppression, which may suggest that predimenol is a potential analgesic and anti-inflammatory agent.

Advancements in stem cell research have enabled the establishment of three-dimensional (3D) primary cell cultures, known as organoids. These culture systems follow the organization of an in vivo organ, as they enclose the different epithelial cell lines of which it is normally composed. Generation of these 3D cultures has bridged the gap between in vitro models, made up by two-dimensional (2D) cancer cell lines cultures, and in vivo animal models, that have major differences with human diseases. Organoids are increasingly used as a model to study colonization of gastric mucosa by infectious agents and to better understand host-microbe interactions and the molecular events that lead to infection, pathogen-epithelial cells interactions and mechanisms of gastric mucosal injury. In this review we will focus on the role of organoids as a tool to investigate molecular interactions of Helicobacter (H.) pylori and Epstein Barr Virus (EBV) and gastric mucosa and how these infections, that affect ≈ 45% of the world population, might progress to gastric cancer, a highly prevalent cancer and the third leading cause of cancer death.

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund's adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.

Background and aim: Chronic Urticaria is an allergic disorder that affects about 0.5 to 5% of the population in different communities. The disease's chronic course and long-term onset impose high economic and psychological costs on communities, adversely affecting individual and social life. Platelets play a role in various pathophysiological processes, including inflammation and immunology. Growing evidence suggests that platelets are actively involved in the pathogenesis of various inflammatory disorders, including inflammatory skin diseases. This study investigated the relationship between platelet and immunoglobulin-E markers and chronic idiopathic urticaria.

Materials and methods: In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements.

Results: 100 patients and 100 healthy persons were evaluated in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001).

Conclusion: The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

Background: Gastrointestinal (GI) cancer is associated with a group of cancers affecting the organs in the GI tract, with a high incidence and mortality rate. This type of cancer development involves a series of molecular events that arise by the dysregulation of gene expressions and microRNAs (miRNAs).

Objectives: This mini-review focuses on elucidating the mechanism of tumor suppressor miRNA-mediated oncogenic gene silencing, which may contribute to a better understanding of miRNA-mediated gene expression regulation of cell cycle, proliferation, invasion, and apoptosis in GI cancers. In this review, the biological significance of tumor suppressor miRNAs involved in gastrointestinal cancers is briefly explained.

Methods: The articles were searched with the keywords 'miRNA', 'gastrointestinal cancers', 'esophageal cancer', 'gastric cancer', 'colorectal cancer', 'pancreatic cancer', 'liver cancer', and 'gall bladder cancer' from the Google Scholar and PubMed databases. A total of 71 research and review articles have been collected and referred for this study.

Results: This review summarises recent research enhancing the effectiveness of miRNAs as novel prognostic, diagnostic, and therapeutic markers for GI cancer treatment strategies. The expression pattern of various miRNAs has been dysregulated in GI cancers, which are associated with proliferation, cell cycle regulation, apoptosis, migration, and invasion.

Conclusion: The role of tumor suppressor miRNAs in the negative regulation of oncogenic gene expression was thoroughly explained in this review. Its potential role as a microRNA therapeutic candidate is also discussed. Profiling and regulating tumor suppressor miRNA expression in gastrointestinal cancers using miRNA mimics could be used as a prognostic, diagnostic, and therapeutic marker, as well as an elucidating molecular therapeutic approach to tumor suppression.

Osteoarthritis (OA) is the most common joint disease worldwide, and its rising prevalence is supported by factors such as obesity and sedentariness. At the molecular level, it is considered an inflammatory disease that leads to the destruction of articular cartilage. Effective therapy to end the degenerative process of arthritis remains elusive, and most therapeutic tools prevent the progress or alleviate the symptoms. By now, medicines for OA are available for oral, topical, or intra-articular (IA) therapy and include analgesics, nonsteroidal anti-inflammatory drugs, corticosteroids, and hyaluronic acid. Compared with conventional oral administration, IA therapy has multiple advantages in terms of bioavailability, efficacy, and toxicity. This review aims to study the underlying beneficial effects of herbal medicine in OA therapy and to open new research perspectives. Herbal medicine administered orally or topically exhibits pharmacological properties that could be relevant for their beneficial effect in OA, mainly anti-inflammatory and antioxidant effects. There are few studies regarding IA injections of plant extracts/ compounds and none related to any combination with agents already used in the clinic. Designing natural pharmaceutical formulations with increased bioavailability that are safe, lack side effects, and are specifically tested, would be a plus for research on medicinal plants and a novelty for the clinic.