Anti-inflammatory Therapy Research Articles

Unraveling Pneumomediastinum in COVID-19 Patients: Insights from a High-Volume-Center Case-Control Study.

Pneumomediastinum (PNM) is a severe complication in COVID-19 patients, potentially exacerbating morbidity and requiring heightened clinical attention. This study aims to identify risk factors, clinical characteristics, and outcomes associated with PNM in COVID-19 patients hospitalized for respiratory failure in our institution. Among 4513 patients admitted in our institution and testing positive for COVID-19 infection during the peak of the COVID-19 pandemic in Italy (1 March 2020 to 31 July 2020), we conducted a single-center, retrospective case-control study focusing our analysis on those with severe disease (respiratory failure). The cohort included a total of 65 patients (32 with PNM and 33 without PNM in the same period). Data were retrospectively collected from hospital records, including demographics, comorbidities, smoking history, clinical and laboratory findings, and imaging results. Statistical analyses were performed using Fisher's exact test and Student's t-test, with significance set at α = 0.05. Patients with PNM were significantly younger (54.9 ± 18.5 vs. 65.4 ± 14.3 years, p = 0.0214) and exhibited higher inflammatory markers, particularly white blood cells count (WBC) at admission (11.4 ± 5.4 vs. 6.5 ± 4.1, p < 0.0001). Although smoking status, body mass index (BMI), and major comorbidities did not differ significantly between groups, COPD was more prevalent in the PNM group (46.9% vs. 15.1%, p = 0.0148). Radiologically, ground-glass opacities (GGOs) and consolidations were more frequent in PNM patients (93.7% vs. 51.5%, p = 0.0002; 78.1% vs. 42.2%, p = 0.0051, respectively). PNM was associated with longer hospital stays (28.5 ± 14.9 vs. 12.0 ± 7.2 days, p < 0.0001) and a higher need for invasive mechanical ventilation (53.1% vs. 30.3%, p = 0.0619). However, mortality rates did not differ significantly between groups. PNM in patients with severe COVID-19 infection is associated with younger age, elevated inflammatory markers, and extensive lung involvement, contributing to increased morbidity and prolonged hospitalization. Early detection and tailored management strategies, including optimized respiratory support and aggressive anti-inflammatory therapies, are crucial in mitigating the adverse outcomes associated with PNM. Further research is needed to validate these findings and improve clinical protocols for managing this complication.

Differential chemoproteomic analysis of RRS-1 candidate molecule and molecules of several nonsteroidal anti-inflammatory drugs

Background. To plan effective and safe pharmacotherapy for inflammation and pain, it is important to evaluate the mechanisms and spectrum of action of nonsteroidal anti-inflammatory drugs (NSAIDs), including their effects on human proteome.Objective: to identify and evaluate the most significant specific differences of candidate molecule RRS-1 (N-{(Z)-2-(1-methyl-1H-indol-3-yl)-1-[(propylamino)carbonyl]vinyl}benzamide) from other NSAIDs through differential chemoreactome analysis.Materials and methods. Chemoproteomic modeling of pharmacological effects of RRS-1 molecule and a number of well-known NSAIDs (diclofenac, nimesulide, ketorolac) on human proteome was carried out on the basis of numerical prediction algorithms over the space of heterogeneous feature descriptions, developed in the topological approach to recognition by Yu.I. Zhuravlev and K.V. Rudakov scientific school.Results. Significant differences in the effects of the studied molecules were found for 1232 proteins of human proteome. The features of assessing interactions of the studied molecules with 47 target proteins, which most distinguished the effects of RRS-1 molecule from all others were identified. RRS-1 could activate adenosine and dopamine receptors, cannabinoid receptor 2 and GABAA receptor to a greater extent than other molecules. Activation of these receptors corresponded to anti-inflammatory, anti-nociceptive and neuroprotective effects. RRS-1 could preferably inhibit a number of pro-inflammatory proteins, receptor bradykinin 1, metabotropic glutamate receptor 5, matrix metalloproteinases 8, 9, 12, and blood coagulation factor X. Additionally, RRS-1 molecule showed preferable inhibition of a number of kinases targeted in antitumor and anti-inflammatory therapy. RRS-1, less than other studied molecules, interacted with the receptors of vitamin D3, thyroid hormone, acetylcholine, cannabinoids and opioids, orexin, and various metabolic enzymes, which is important in assessment of the safety of using drugs based on this molecule. RRS-1 characteristically exhibited a moderate profile of antivitamin action: the total score of vitamin and mineral loss (7.4±3.7) was significantly less in comparison to diclofenac (11.7±4.5) and was actually on the same level as nimesulide (6.9±3.7) and ketorolac (6.7±3.6).Conclusion. Chemoreactomic and chemoproteomic profiling of RRS-1 candidate molecule provided pre-experimental assessments of its efficacy and safety through modeling interactions with the human proteome.

Development and Novel Therapeutics in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a complication of diabetes mellitus which causes retinal damage which when left untreated will cause visual problems. As the prevalence of DR increases over the years, there is a need to optimise the currently available treatments as well as developing novel drugs to improve the therapy provided for the patients in the clinical practice. Several pharmacological therapies like, anti-vascular endothelial growth factor and anti-inflammatory therapies which include intravitreal, and implant of corticosteroids are significant in the management to decrease the risk of DR-related vision impairment. Clinical trials for novel drug therapies are still ongoing till this day to enhance the efficacy of DR treatment. Even though there are also modern treatments such as laser therapy for the patients, prevention should be done to lower the number of individuals affected by DR. Due to the complexity of DR, there are numerous obstacles to develop new medications for DR which include the increasing healthcare cost of DR treatment. New insights such as utilisation of artificial intelligence will be implemented into the management of DR as it has proved its potential in aiding the screening process. In parallel with the increase in DR prevalence and the number of treatments developed, extensive understanding of the mechanism of action of DR should be further improved to prevent more complications in the future. This review summarises the epidemiological trend, prevention strategies, challenges in treatment, current novel therapeutics (including drugs under clinical trials), future therapeutic trends and possibilities for implementing AI in the early diagnosis and management of DR.

Contributions of Inflammation to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

The most common form of heart failure is heart failure with preserved ejection fraction (HFpEF). While heterogeneous in origin, the most common form of HFpEF is the cardiometabolic manifestation. Obesity and aging promote systemic inflammation that appears integral to cardiometabolic HFpEF pathophysiology. Accumulation of immune cells within the heart, fueled by an altered metabolome, contribute to cardiac inflammation and fibrosis. In spite of this, broad anti-inflammatory therapy has not shown significant benefit in patient outcomes. Thus, understanding of the nuances to metabolic and age-related inflammation during HFpEF is paramount for more targeted interventions. Here, we review clinical evidence of inflammation in the context of HFpEF and summarize our mechanistic understanding of immunometabolic inflammation, highlighting pathways of therapeutic potential along the way.

Systemic Inflammation Predict Neurological Functional Outcome in Patients with Tuberculous Meningitis: A Multicenter Retrospective Cohort Study in China.

The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment. Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels. A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14-1.33; P<0.001), and poor outcome (OR=1.34; 95% CI, 1.26-1.45; P<0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42-1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49-2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification. Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.

INTRAVITREAL 0.18-mg FLUOCINOLONE ACETONIDE IMPLANT FOR PEDIATRIC UVEITIS.

This study reports the outcomes of the 0.18-mg intravitreal fluocinolone acetonide implant in the treatment of pediatric noninfectious uveitis. A retrospective cohort study was performed on patients under 18 years old who received fluocinolone acetonide implant between June 1, 2020 and March 1, 2023. Data collected included demographics, uveitis diagnosis, use of anti-inflammatory therapy, visual acuity, intraocular pressure, and grading of uveitis activity. Uveitis recurrence was defined as increased inflammation that required additional anti-inflammatory therapy. Eleven eyes from seven patients were included in this study. One patient (one eye) had a diagnosis of immune recovery uveitis and the remaining six patients (10 eyes) had pars planitis. The rate of remaining recurrence-free was 82% at 6 months, 60% at 12 months, and 60% at 24 months. Two of the six phakic eyes at baseline required cataract extraction during follow-up. Two of the four eyes that did not have intraocular pressure-lowering surgery before implantation required surgery in follow-up. The 0.18-mg fluocinolone acetonide implant has a similar efficacy for the treatment of pediatric uveitis, particularly pars planitis, as in the adult population, although with higher rates of ocular hypertension requiring intervention.

Mesoporous Polydopamine Nanotherapeutics for MRI-Guided Cancer Photothermal and Anti-Inflammatory Therapy.

As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence. In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs' anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer. The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.

Application Value of Platelet-to-Lymphocyte Ratio as a Novel Indicator in Rheumatoid Arthritis: A Review Based on Clinical Evidence.

Rheumatoid arthritis (RA) is a chronically progressive autoimmune disease with increasing age-standardized prevalence and incidence of RA worldwide. Its pathological features are persistent synovitis of the joint, accompanied by the release of a large number of inflammatory cytokines and cartilage and bone destruction. RA can lead to progressive joint damage, stiffness and swelling, vascular and bone-related complications, and irreversible disability, which seriously affects patients' life treatment. Early diagnosis and treatment can enhance the quality of life of RA patients. Platelet-to-lymphocyte ratio (PLR), as a common indicator in routine blood tests, has been proposed as an indicator of systemic inflammation in recent years. Its clinical detection is less invasive, economical, rapid and simple, and has been applied to the clinical evaluation of a variety of diseases. Of note, this indicator is important in assessing disease activity in RA, co-diagnosing RA, detecting subclinical complications, and monitoring responses to anti-inflammatory therapy. Therefore, this review summarizes the relationship between PLR and RA and the relevant mechanisms, further advancing the understanding of the clinical value of PLR.

Exploring the therapeutic potential of Xiangsha Liujunzi Wan in Crohn's disease: from network pharmacology approach to experimental validation

Ethnopharmacological relevanceXiangsha Liujunzi Wan (LJZW) is a traditional Chinese medicine (TCM) formula containing a variety of traditional Chinese herb components. Its principal components are often used in the treatment of gastrointestinal diseases and contribute to the treatment of Crohn's disease (CD). Aim of the studyTo explore the therapeutic potential of LJZW in CD through network pharmacology, bioinformatics, molecular docking, and experimental verification. MethodsThe principal bioactive components and corresponding targets of LJZW were ascertained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Potential targets for CD were identified in GeneCards, OMIM, DrugBank, DisGeNET, CTD, and Gene Expression Omnibus (GEO) databases. Intersection targets of LJZW and CD were identified using a Venn diagram and visualized using Cytoscape 3.8.0 to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to assess the function of intersection targets. AutoDockTools and PyMOL were used for molecular docking to recognize the association between the core ingredients of LJZW and the core targets of CD. Subsequently, a series of experiments were conducted for validation. ResultsThe network pharmacology results indicated that there were 156 bioactive components and 268 corresponding targets for LJZW, 3023 primary relevant targets for CD, and 169 intersection targets for LJZW and CD. The PPI network was employed to identify five hub genes and six clusters. The GO functional analysis indicated that intersection targets are primarily correlated with oxidative stress and inflammatory responses. KEGG pathway analysis revealed that these targets were primarily associated with the phosphotylinosital 3 kinase (PI3K)-protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results showed that the core ingredients of LJZW had good binding ability with the core targets of CD. A series of experiments demonstrated that LJZW could effectively attenuate TNBS-induced colitis symptoms, inhibit the inflammatory response, and protect intestinal barrier function by inhibiting the PI3K-AKT and MAPK signaling pathways, thus preventing and treating CD. ConclusionLJZW has the characteristics of multi-component, multi-target, and multi-pathway treatment, which helps to improve the treatment of CD, protect the intestinal barrier, and exert the effect of anti-inflammatory therapy by inhibiting PI3K-AKT and MAPK signaling pathways.

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.

Assessment of liver and kidney function in patients with ankylosing spondylitis on long-term non-steroidal anti-inflammatory drug therapy.

This study aimed to analyze the status of liver [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and kidney (serum creatine) function in ankylosing spondylitis (AS) patients assuming continuously non-steroidal anti-inflammatory drugs (NSAIDs) alone over a long period. Between 2013 and 2022, there were records of 385 AS patients. Of them, 56 were receiving only NSAIDs, and the files of these patients were retrospectively analyzed. Demographic and clinical characteristics were collected. Blood tests, including serum creatinine, AST, and ALT, were assessed at each visit. Of the 56 patients, 39 were male. The mean age was 45.30 years, and the follow-up period was 9.80 years. Of them, 44.6% used indomethacin, 26.8% naproxen, 17.9% diclofenac, 5.4% acemethazine, 3.6% meloxicam, and 1.8% celecoxib. The mean baseline serum creatinine was 0.71 mg/dL. The mean baseline serum AST and ALT were 19.6 u/L and 22.9 u/L, respectively. Baseline creatinine, AST, and ALT were not statistically significantly different between sexes. There was a statistically significant difference between mean creatinine concentrations at baseline and at year 3. One patient on naproxen discontinued treatment due to elevated creatinine. The creatinine level decreased during the patient's follow-up. Liver enzymes above 3 times the normal value were not seen in any patient. Based on real-world data, long-term use of NSAIDs has generally not led to acute liver and kidney injury or progressive impairment of hepatorenal function requiring discontinuation of treatment.

Colonoscopy diagnosis of recurrent abdominal pain in a 4-year-old boy with intestinal duplication cyst involving colon, appendix, and ileum: a case report

BackgroundIntestinal duplication cyst is an infrequent congenital malformation that can involve all the segments of the gastrointestinal tract. The cases of intestinal duplication cyst involving the colon, appendix, and ileum in children are particularly uncommon. The symptoms of abdominal pain are similar to other acute abdominal diseases in children, such as appendicitis, intussusception, and intestinal obstruction, so sometimes its diagnosis is challenging and leads to misdiagnosis.Case presentationWe report a 4-year-old Asian boy who presented to the pediatric emergency department with abdominal pain and vomiting but no fever, peritonitis, or mass. No abdominal abnormality was found via radiology and ultrasonography. After 2 days’ anti-inflammatory therapy, the patient was discharged with pain relief. A total of 9 months later, he was readmitted to the pediatric emergency department for the same complaint as the first admission. Abdominal physical examination and ultrasound examination were still negative. Barium examination found a large mass in the colon. Colonoscopy was performed before operation to confirm the rare co-cavity intestinal duplication cyst involving the colon, appendix, and ileum. After resection of intestinal duplication and ileocolonic anastomosis, the patient’s abdominal pain and vomiting has not recurred for 5 years postoperatively.ConclusionsThe diagnosis of intestinal duplication cyst in children is difficult, especially the rare co-cavity and long segmental intestinal duplication, which is easily misdiagnosed. Colonoscopy may be an effective auxiliary diagnostic method, especially for diseases that are difficult to diagnosed clinically, such as recurrent abdominal pain.

Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common lung complication of prematurity. Despite extensive research, our understanding of its pathophysiology remains limited, as reflected by the stable prevalence of BPD. Prematurity is the primary risk factor for BPD, with oxidative stress (OS) and inflammation playing significant roles and being closely linked to premature birth. Understanding the interplay and temporal relationship between OS and inflammation is crucial for developing new treatments for BPD. Animal studies suggest that OS and inflammation can exacerbate each other. Clinical trials focusing solely on antioxidants or anti-inflammatory therapies have been unsuccessful. In contrast, vitamin A and caffeine, with antioxidant and anti-inflammatory properties, have shown some efficacy, reducing BPD by about 10%. However, more than one-third of very preterm infants still suffer from BPD. New therapeutic agents are needed. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), is a reversible myeloperoxidase inhibitor and a systems pharmacology agent. It reduces BPD severity by inhibiting MPO, enhancing antioxidative proteins, and alleviating endoplasmic reticulum stress and cellular senescence in a hyperoxia rat model. KYC represents a promising new approach to BPD treatment.

Application of Ensemble Machine Learning Methods for QSAR Classification of Leukotriene A4 Hydrolase Inhibitors in Drug Discovery

Inflammatory diseases such as asthma, rheumatoid arthritis, and cardiovascular conditions are driven by overproduction of leukotriene B4 (LTB4), a potent inflammatory mediator. Leukotriene A4 hydrolase (LTA4H) plays a critical role in converting leukotriene A4 into LTB4, making it a prime target for drug discovery. Despite ongoing efforts, developing effective LTA4H inhibitors has been challenging due to the complex binding properties of the enzyme and the structural diversity of potential inhibitors. Traditional drug discovery methods, like high-throughput screening (HTS), are often time-consuming and inefficient, prompting the need for more advanced approaches. Quantitative Structure-Activity Relationship (QSAR) modeling, enhanced by ensemble machine learning techniques, provides a promising solution by enabling accurate prediction of compound bioactivity based on molecular descriptors. In this study, six ensemble machine learning methods—AdaBoost, Extra Trees, Gradient Boosting, LightGBM, Random Forest, and XGBoost—were employed to classify LTA4H inhibitors. The dataset, comprising 636 compounds labeled as active or inactive based on pIC50 values, was processed to extract 450 molecular descriptors after feature engineering. The results show that the LightGBM model achieved the highest classification accuracy (83.59%) and Area Under the Curve (AUC) value (0.901), outperforming other models. XGBoost and Random Forest also demonstrated strong performance, with AUC values of 0.890 and 0.895, respectively. The high sensitivity (95.24%) of the XGBoost model highlights its ability to accurately identify active compounds, though it exhibited slightly lower specificity (61.36%), indicating a higher false-positive rate. These findings suggest that ensemble machine learning models, particularly LightGBM, are highly effective in predicting bioactivity, offering valuable tools for early-stage drug discovery. The results indicate that ensemble methods significantly enhance QSAR model accuracy, making them viable for identifying promising LTA4H inhibitors, potentially accelerating the development of anti-inflammatory therapies.

Euterpe oleracea Mart. Bioactive Molecules: Promising Agents to Modulate the NLRP3 Inflammasome.

Inflammation is a vital mechanism that defends the organism against infections and restores homeostasis. However, when inflammation becomes uncontrolled, it leads to chronic inflammation. The NLRP3 inflammasome is crucial in chronic inflammatory responses and has become a focal point in research for new anti-inflammatory therapies. Flavonoids like catechin, apigenin, and epicatechin are known for their bioactive properties (antioxidant, anti-inflammatory, etc.), but the mechanisms behind their anti-inflammatory actions remain unclear. This study aimed to explore the ability of various flavonoids (isolated and combined) to modulate the NLRP3 inflammasome using in silico and in vitro models. Computer simulations, such as molecular docking, molecular dynamics, and MM/GBSA calculations examined the interactions between bioactive molecules and NLRP3 PYD. THP1 cells were treated with LPS + nigericin to activate NLRP3, followed by flavonoid treatment at different concentrations. THP1-derived macrophages were also treated following NLRP3 activation protocols. The assays included colorimetric, fluorometric, microscopic, and molecular techniques. The results showed that catechin, apigenin, and epicatechin had high binding affinity to NLRP3 PYD, similar to the known NLRP3 inhibitor MCC950. These flavonoids, particularly at 1 µg/mL, 0.1 µg/mL, and 0.01 µg/mL, respectively, significantly reduced LPS + nigericin effects in both cell types and decreased pro-inflammatory cytokine, caspase-1, and NLRP3 gene expression, suggesting their potential as anti-inflammatory agents through NLRP3 modulation.

A Narrative Review of Post-traumatic Neuroinflammation: Relevance to Pediatrics.

This is a narrative review that explores the complex interaction between post-traumatic neuroinflammation and its importance in pediatric traumatic brain injuries (TBIs). For immediate and long-term consequences of TBI, neuroinflammation, manifested by activation of microglia and astrocytes, secretion of pro-inflammatory cytokines, as well as breakdown of the blood-brain barrier, are critical factors. While inflammation is an essential part of the brain's repair systems, excessive or prolonged neuroinflammation can lead to more significant neuronal damage, which, in turn, causes persistent cognitive and behavioral deficits over time. In this regard, the paper synthesizes existing evidence concerning molecular and cellular mechanisms that underlie neuroinflammation in relation to TBIamong children, paying attention to age disparities in inflammatory response and their implications for treatment and recovery. Furthermore, it explores how targeted anti-inflammatory therapies are highly likely to improve outcomes for pediatric patients. The outcomes emphasize that there is a need for a more comprehensive understanding of child neuroinflammatory processes and age-specific therapeutic approaches aimed at lessening the effects' negative impacts after brain injury occurs.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionThe systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional...

The Role of Inflammation in the Pathogenesis of Cardiogenic Shock Secondary to Acute Myocardial Infarction: A Narrative Review.

Cardiogenic shock (CS) is one of the most serious complications of myocardial infarction (MI) with a high mortality rate. The timely and effective prevention and early suppression of this adverse event may influence the prognosis and outcome in patients with MI complicated by CS (MI CS). Despite the use of existing pharmaco-invasive options for maintaining an optimal pumping function of the heart in patients with MI CS, its mortality remains high, prompting the search for new approaches to pathogenetic therapy. This review considers the role of the systemic inflammatory response in the pathogenesis of MI CS. The primary processes involved in its initiation are described, including the progression from the onset of MI to the generalization of the inflammatory response and the development of multiple organ dysfunction. The approaches to anti-inflammatory therapy in patients with CS are discussed, and further promising research directions are outlined. In this review, we updated and summarized information on the inflammatory component of MI CS pathogenesis with a particular focus on its foundational aspects. This will facilitate the identification of specific inflammatory phenotypes and endotypes in MI CS and the development of targeted therapeutic strategies for this MI complication.

Hemostasis correction in the treatment and rehabilitation of COVID-19 patients

Background. It is well known that the severe course of a new coronavirus infection (NCI) is often accompanied by a significant risk of hemostasis system disorders. Virus-associated coagulopathy in COVID-19 differs from its other types. Apparently, it is directly related to inflammatory processes and an inadequate response from the immune system.Objective: to determine the main mechanisms of immune-mediated coagulopathy development in NCI patients and methods of correcting this pathological condition.Material and methods. The search for studies devoted to the specifics of coagulopathy course in COVID-19, treatment and rehabilitation of patients with this complication was carried out in international scientific research databases PubMed/ MEDLINE, Google Scholar, ScienceDirect and scientific electronic library (eLibrary). The search depth was 20 years. The results of queries in search engines Yandex and Google were also taken. After selection of publications performed according to PRISMA recommendations, 73 articles were included in the review.Results. A “vicious circle” associated with cytokine storm underlies the pathogenetic mechanisms of immune-mediated thrombosis in COVID-19 patients. A significant role of endothelial dysfunction, extracellular neutrophil traps (NETs), thrombocytopathy and changes in complement system activity is assigned to coagulopathy development. The therapy of this complication is aimed primarily at pathogenetic process. The effectiveness of anticoagulants, anti-inflammatory drugs, antiplatelet agents, drugs aimed at limiting the role of NETs and complement system in thrombosis development was shown. The expediency of preventive use of anticoagulants in COVID-19 patients was considered. Information was provided on the rehabilitation of NCI patients with coagulopathy. The effectiveness of combined anti-inflammatory and anticoagulant therapy in COVID-19 as a component of complex rehabilitation was indicated.Conslusion. Inflammatory processes and immune response play an crucial role in coagulopathy development in NCI patients. The combination of all pathogenetic changes on the part of immune system, inflammatory response and hemostasis system makes it difficult to carry out therapeutic measures. The general scheme of rehabilitation for COVID-19 patients should include three stages, and timely use of combined anti-inflammatory and anticoagulant therapy is also advisable.

Oxylipins in Aqueous Humor of Primary Open-Angle Glaucoma Patients.

Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients. Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness. This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG.