Anti-inflammatory Research Articles

Greenness and whiteness assessment of a sustainable voltammetric method for difluprednate estimation in the presence of its alkaline degradation product.

Nowadays, scientists are currently attempting to lessen the harmful effects of chemicals on the environment. Stability testing identifies how a drug's quality changes over time. The current work suggests a first and sustainable differential pulse voltammetry technique for quantifying difluprednate (DIF) as an anti-inflammatory agent in the presence of its alkaline degradation product (DEG). The optimum conditions for the developed method were investigated with a glassy carbon electrode and a scan rate of 100mVs-1. The linearity range was 2.0 × 10-7-1.0 × 10-6M for DIF. DIF was found to undergo alkaline degradation, when refluxed for 8h using 2.0M NaOH, and DEG was successfully characterized utilizing IR and MS/MS. The intended approach demonstrated the selectivity for DIF identification in pure, pharmaceutical, and degradation forms. The student's t-test and F value were used to compare the suggested and reported approaches statistically. The results were validated according to ICH requirements. The greenness of the studied approach was evaluated using the Green Analytical Procedure Index and the Analytical Greenness metric. Additionally, the whiteness features of the proposed approach were examined with the recently released red, green, and blue 12 model, and the recommended strategy performed better than the reported approaches in greenness and whiteness.

Nanoemulsions Based on Soluble Chenopodin/Alginate Complex for Colonic Delivery of Quercetin

Inflammatory bowel disease (IBD) is an autoimmune disorder caused by uncontrolled immune activation and the subsequent destruction of the colon tissue. Quercetin (Qt) is a natural antioxidant and anti-inflammatory agent proposed as an alternative to mitigate IBD. However, its use is limited by its low oral bioavailability. This study aimed to develop nanoemulsions (NEs) based on a soluble chenopodin/alginate (QPA) complex and Tween 80 (T80), intended for the colonic release of Qt, activated by the pH (5.4) and bacteria present in the human colonic microbiota. NEs with different ratios of QPA/Tw80 (F1-F6) were prepared, where F4Qt (60/40) and F5Qt (70/30) showed sizes smaller than 260 nm, PDI < 0.27, and high encapsulation efficiency (>85%). The stability was evaluated under different conditions (time, temperature, pH, and NaCl). The DSC and FTIR analyses indicated hydrophobic and hydrogen bonding interactions between QPA and Qt. F4Qt and F5Qt showed the greater release of Qt in PBS1X and Krebs buffer at pH 5.4 (diseased condition), compared to the release at pH 7.4 (healthy condition) at 8 h of study. In the presence of E. coli and B. thetaiotaomicron, they triggered the more significant release of Qt (ƒ2 < 50) compared to the control (without bacteria). The NEs (without Qt) did not show cytotoxicity in HT-29 cells (cell viability > 80%) and increased the antioxidant capacity of encapsulated Qt. Therefore, these NEs are promising nanocarriers for the delivery of flavonoids to the colon to treat IBD.

Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis.

Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. Open Science Framework: https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Effect ratio of stearic acid and oleic acid on characteristics of diclofenac sodium nanostructured lipid carrier

Background: Osteoarthritis treatment generally involves using a Non-steroidal Anti-inflammatory Drug (NSAID), and the most common is Diclofenac sodium. The oral use of diclofenac sodium presents some adverse effects on the gastrointestinal tract. Trans-dermal diclofenac sodium's biological efficacy can be affected by factors including its log P value of 1.13. Nanostructured Lipid Carrier (NLC) may solve these concerns. Objective: This study examined how stearic and oleic acid concentrations customise diclofenac sodium NLC's physicochemical properties. Method: High shear homogenisation was used to compare stearic acid and oleic acid at 6:4, 7:3, and 8:2. Furthermore, the physicochemical properties of diclofenac sodium NLC were assessed, such as organoleptic, particle size and poly-dispersity index, pH, viscosity, zeta potential, entrapment efficiency, profiles of FTIR and DSC. Result: This study found that particle size ranged from 333.60 ± 144.29 to 791.77 ± 85.57, and entrapment efficiency was 89.38 ± 3.69 to 76.96 ± 3.29. Increasing the content of oleic acid as a liquid lipid reduces particle size and improves diclofenac sodium NLC entrapment. According to One-Way ANOVA, the dependent variable was not significantly affected by any independent variables (p-value > 0.05) except for particle size and entrapment efficiency. Conclusion: Stearic acid-oleic acid concentration ratios affect diclofenac sodium NLC's physicochemical properties.

Probiotic bacteria protect against indomethacin-induced gastric ulcers through modulation of oxidative stress, inflammation, and apoptosis.

Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin. Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant. As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05). Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia

Objective: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3′,4′-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. Materials and Methods: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1β, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. Results: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. Conclusions: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Risk factor analysis of vertebral fractures requiring surgery in patients with ankylosing spondylitis.

This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS). We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group. At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis. CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.

Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization

BackgroundNumerous epidemiological studies have elucidated the intricate connection between inflammation and cancer, highlighting how sustained inflammatory responses can fuel carcinogenesis by fostering proliferation, angiogenesis, and metastasis, while dampening immune responses and sensitivity to chemotherapy. Previous clinical investigations have underscored the potential of anti-inflammatory medications in either preventing or mitigating tumor formation. Here, the causal relationship between anti-inflammatory drugs and cancer was further explored through Mendelian randomization studies.MethodsEmploying Mendelian randomization, we scrutinized the causal links between three anti-inflammatory drugs—NSAIDs, Aspirin, and Anilide—and 37 types of cancer. We primarily utilized inverse variance weighting (IVW) as the primary analytical approach to delineate the causal association between these drugs and cancer types. Concurrently, sensitivity analyses were conducted to ascertain the absence of horizontal pleiotropy and heterogeneity.ResultsOur investigation revealed a discernible causal relationship between certain anti-inflammatory drugs and a subset of cancers, albeit without a pervasive impact across all cancer types. Specifically, NSAIDs exhibited a risk-reducing effect on non-small cell lung cancer (OR: 0.76, 95% CI: 0.59–0.97, p-value: 0.03) and gastric cancer (OR: 0.57, 95% CI: 0.34–0.98, p-value: 0.04). Conversely, aspirin was associated with an increased risk of oral malignant tumors (OR: 2.18, 95% CI: 1.13–4.21, p-value: 0.02). Notably, no statistically significant findings were observed for anilide drugs (p &amp;lt; 0.05).ConclusionWe identified several cancers with potential causal links to NSAIDs, including non-small cell lung cancer and gastric cancer. Despite our extensive analysis, we did not identify a substantial causal relationship between the use of anti-inflammatory drugs and the development of various cancers.

Anti-Inflammatory Effects of GPR55 Agonists and Antagonists in LPS-Treated BV2 Microglial Cells

Chronic inflammation is driven by proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and chemokines, such as c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10. Inflammatory processes of the central nervous system (CNS) play an important role in the pathogenesis of various neurological and psychiatric disorders like Alzheimer’s disease, Parkinson’s disease, and depression. Therefore, identifying novel anti-inflammatory drugs may be beneficial for treating disorders with a neuroinflammatory background. The G-protein-coupled receptor 55 (GPR55) gained interest due to its role in inflammatory processes and possible involvement in different disorders. This study aims to identify the anti-inflammatory effects of the coumarin-based compound KIT C, acting as an antagonist with inverse agonistic activity at GPR55, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells in comparison to the commercial GPR55 agonist O-1602 and antagonist ML-193. All compounds significantly suppressed IL-6, TNF-α, CCL2, CCL3, CXCL2, and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compounds are partially explained by modulation of the phosphorylation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC) pathways, and the transcription factor nuclear factor (NF)-κB, respectively. Due to its potent anti-inflammatory properties, KIT C is a promising compound for further research and potential use in inflammatory-related disorders.

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches.

Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor with a dismal prognosis despite current treatment strategies. Inflammation plays an essential role in GBM pathophysiology, contributing to tumor growth, invasion, immunosuppression, and angiogenesis. As a result, pharmacological intervention with anti-inflammatory drugs has been used as a potential approach for the management of GBM. To provide an overview of the current understanding of GBM pathophysiology, potential therapeutic applications of anti-inflammatory drugs in GBM, conventional treatments of glioblastoma and emerging therapeutic approaches currently under investigation. A narrative review was carried out, scanning publications from 2000 to 2023 on PubMed and Google Scholar. The search was not guided by a set research question or a specific search method but rather focused on the area of interest. Conventional treatments such as surgery, radiotherapy, and chemotherapy have shown some benefits, but their effectiveness is limited by various factors such as tumor heterogeneity and resistance.

Communications between Neutrophil–Endothelial Interaction in Immune Defense against Bacterial Infection

The endothelial barrier plays a critical role in immune defense against bacterial infection. Efficient interactions between neutrophils and endothelial cells facilitate the activation of both cell types. However, neutrophil activation can have dual effects, promoting bacterial clearance on one hand while triggering inflammation on the other. In this review, we provide a detailed overview of the cellular defense progression when neutrophils encounter bacteria, focusing specifically on neutrophil–endothelial interactions and endothelial activation or dysfunction. By elucidating the underlying mechanisms of inflammatory pathways, potential therapeutic targets for inflammation caused by endothelial dysfunction may be identified. Overall, our comprehensive understanding of neutrophil–endothelial interactions in modulating innate immunity provides deeper insights into therapeutic strategies for infectious diseases and further promotes the development of antibacterial and anti-inflammatory drugs.

Kallopterolides A–I, a New Subclass of seco-Diterpenes Isolated from the Southwestern Caribbean Sea Plume Antillogorgia kallos

Kallopterolides A–I (1–9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1–9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.

Collagen hydrogel protects intestinal epithelial cells from indomethacin-induced damage: results of an in vitro experiment

INTRODUCTION. Indomethacin is a derivative of indoleacetic acid and has anti-inflammatory, analgesic and antipyretic effects. However, the results of numerous studies show that indomethacin, like many other nonsteroidal anti-inflammatory drugs (NSAIDs), have an inhibitory effect on the viability and functional activity of enterocytes. In this regard, the search for new ways to reduce the severity of side effects from the use of NSAIDs remains relevant. One of these approaches may be to enrich patients’ diets with non-drug biologically active compounds, including proteins. However, the effect of dietary proteins and biologically active peptides on NSAID-induced damage to the wall of the small intestine and stomach has not been sufficiently studied. AIM. To evaluate the ability of a collagen-containing dietary supplement to protect human duodenal epithelial cells (HuTu-80 line) from indomethacin-induced damage. MATERIALS AND METHODS. The composite collagen-containing hydrogel was provided by «FIRST ALIVE COLLAGEN» LLC (Russia) and is a registered dietary supplement. The work used a commercial culture of human skin fibroblast cells and human duodenal epithelial cells (line HuTu-80). The viability of intestinal cells and fibroblasts was assessed using light and fluorescence microscopy and flow cytometry methods. RESULTS AND DISCUSSION. It has been established that indomethacin inhibits cell growth, causes apoptosis and death of enterocytes, and also leads to the accumulation of cells in the S-phase, which indicates a disruption in the regulation of the cell cycle. It was revealed that collagen hydrogel prevents cell death caused by indomethacin and reduces the number of apoptotic cells in the population. The protective effect of collagen hydrogel is characterized by normalization of the cell cycle of enterocytes and restoration of their growth and proliferative activity. CONCLUSION. Thus, collagen hydrogel, in vitro, is able to reduce the pathogenic effect of indomethacin on human intestinal epithelial cells. The protective effect of collagen hydrogel is characterized by maintaining viability, inhibiting apoptotic processes, and maintaining cell cycle stability. The results obtained indicate the prospects of using a dietary supplement based on a composite collagen hydrogel as a prophylactic agent to reduce the risk of NSAID-associated gastrointestinal diseases. However, to confirm the therapeutic effectiveness of the dietary supplement, further research is necessary, both using experimental animal modeling of NSAID-associated diseases of the human gastrointestinal tract, and clinical studies.

Algorithm for the development of a multicomponent pharmaceutical substance of plant origin with antimicrobial action: from science search to dosage form

Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.

Construction of janus mesenchymal stem cell-hitchhiked melanin nanoparticles to modulate the Th17/Treg balance for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a common chronic inflammatory disease capable of causing the disability. Although various antioxidant strategies have been attempted for prevention and treatment of RA through scavenging the free radicals, the therapeutic effect is limited. Recently, it is reported that the unremitting course of RA intensely correlates with the persistence of immunologic memory, in which the imbalance of T helper 17 (Th17) cells/regulatory T (Treg) cells plays an important role. Herein, we constructed Janus mesenchymal stem cell (MSC)-hitchhiked melanin nanoparticles (MSCFM) for RA therapy, where one half of MSC kept intact for chemotactically migrating towards the RA inflammatory sites and efficiently restoring the Th17/Treg balance based on the property of MSCs, while the other half hitchhiked the iron-doped melanin (FM) nanoparticles (NPs) and release them to scavenge free radicals for maintaining the durability of Th17/Treg balance. In vitro studies indicated MSCFM could migrate towards CXCL12 inflammatory cytokine, scavenge reactive oxygen and nitrogen species, inhibit Th17 cell proliferation and induce Treg cell production. Further in vivo studies corroborated that intravenously injected MSCFM could target the RA site of collagen-induced arthritis mouse model and alleviate the pathological progression of RA. MSCFM holds great potential as an anti-inflammatory agent for RA management.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome - a rare differential for anterior neck pain - Series of 3 cases and review of literature.

We report a series of 3 cases of transient perivascular inflammation of the carotid artery (TIPIC) syndrome in an otherwise healthy individual. We would also like to review this rare entity and compare it with other similar cases reported in the literature. Our first case was a young male with right-sided neck pain of 1-week duration with magnetic resonance imaging (MRI) showing right carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the second case, a young male presented with left-sided neck pain and odynophagia of 5 days duration with an MRI showing left carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the third case a young male presented with right-sided neck pain of 1-day duration with an MRI showing right common carotid perivascular inflammation near the bifurcation with complete resolution in pain but with residual wall thickening. We want to highlight the existence of this new entity by reporting these 3 case series with a brief review of the literature. The cause and pathogenesis of this rare entity remain unknown. It has been hypothesized to be autoimmune or viral-mediated inflammation which requires further understanding.

#3095 Pinpointing specific circulating microRNAs as putative biomarkers for chronic kidney disease and cardiovascular outcomes

Abstract Background and Aims Chronic kidney disease (CKD) affects over 10% of the worldwide population and entails a significant risk for cardiovascular disease (CVD), leading to an up to 500-fold increase in cardiovascular mortality in advanced stages. However, the pathophysiological mechanisms underlying kidney-heart intercommunication remain unknown. In recent years, microRNAs (miRNAs) emerged as critical regulators of gene expression and numerous miRNAs that have been implicated in both CKD and CVD pathogenesis. Still, so far, their role in kidney-heart crosstalk has not been addressed. In this study, we evaluated the expression of a panel of miRNAs in plasma from pre-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow up. Method The expression levels of miR-30c-5p, miR-132-3p, miR-199a-5p, and miR-324-3p was assessed by real time qRT-PCR in plasma samples from two cohorts of pre-dialysis CKD patients followed up at the Nephrology Department of Centro Hospitalar Universitário de São João (CHSJ, Porto, Portugal).The discovery cohort was established between November 2014 and August 2018 and comprises 52 CKD patients while the validation cohort comprises samples from 43 CKD patients who underwent a kidney biopsy for diagnostic purposes from November 2019 to December 2022. Patients with acute kidney injury, neoplasia diagnosis, recent infections (&amp;lt;1 week), or known psychiatric disorders were excluded from the study. Plasma samples from 38 healthy blood donors, recruited at the Immunohemotherapy Department of CHSJ, in which creatinine values were measured and considered normal were used as controls. Participants with a history of cancer, inflammatory, or infectious diseases and who were being treated with anti-inflammatory or anti-depressive drugs, were excluded. MiRs expression in comparison with the controls was validated in both cohorts and its expression in the Discovery cohort was correlated with the patients clinical data in a 5 year follow up. Results Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients compared with healthy controls, presenting a significant power to discriminate the disease condition. Still, considering the stratification of CKD in early/moderate (1-3) and advanced stages (4-5), only miR-30c-5p presented a decreased expression in the initial stages of the disease, showing a significant diagnostic value as an early biomarker for CKD, independently of eGFR. When analyzing the major disease outcomes in a 5 year time, miR-199a-5p was associated with increased frequency of CVD and mortality while miR-324-3p was downregulated in CKD patients that progressed to worse stages. Conclusion These findings highlight miR-30c-5p as a potential biomarker for the diagnosis of CKD in early stages of the disease and identify, for the first time, the enrollment of miR-199a-5p and miR-324-3p in kidney-heart pathophysiological crosstalk, paving the way for the putative establishment of new biomarkers and therapeutic targets for CKD and its outcomes.

Synthesis and application of gold nanoparticles as antioxidants

Non-communicable diseases (NCDs) and premature aging, caused by free radicals, have spurred a demand for extensive research into finding effective antioxidants. Currently, there is an abundance of both natural and synthetic antioxidants, including metal nanoparticles with high antioxidant activity. Among these, gold nanoparticles (AuNPs) stand out as favoured antioxidants because of their minimal toxicity, simple synthesis, and detectability. The antioxidant properties of AuNPs enhance its wide-ranging potential for use in healthcare including applications as anti-aging, anti-inflammatory, and wound healing agents, as well as treatment for various diseases. This review highlights recent progress in the synthesis of AuNPs as antioxidants and method for assessing their antioxidant capacity as well as delves into their mechanism of action and explores their potential health applications. In conclusion, considering the physicochemical and biological properties, along with the benefits and potential challenges for future development, AuNPs are deemed promising and effective antioxidants suitable for clinical applications.

#1408 Dehydration cannot substitute for any of the triple whammy drugs to cause acute kidney injury

Abstract Background and Aims Polymedication in patients with chronic diseases, such as hypertension, can lead to undesired drug interactions. The combination of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) with diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) can cause triple whammy (TW)-induced acute kidney injury (TW-AKI). Up to 9% of hypertensive patients used NSAIDs in combination with ACEIs / ARBs and diuretics. AKI has a mortality rate of 40% and TW increases the risk of AKI by 30% compared to the combination of only two drugs. In addition, TW-AKI is associated with other risk factors such as dehydration, which may exacerbate the injury. Consequently, the aim of our study was to determine whether dehydration combined with two of the TW drugs could induce AKI in an in vivo experimental model. Method Three months old male Spontaneously Hypertensive Rats (SHR) were divided into four experimental groups: control group (CT); TW group (TW), which received four days of double therapy with trandolapril and furosemide, followed by a triple therapy for two days with trandolapril, furosemide and ibuprofen; trandolapril and ibuprofen group (T+I), which received four days of trandolapril followed by two days of trandolapril and ibuprofen; furosemide and ibuprofen group (F+I), which received four days of furosemide followed by two days of furosemide and ibuprofen; and trandolapril and furosemide group (T+F), which received six days of trandolapril and furosemide. All groups were subjected to a 60-70% water restriction of basal intake (i.e. 15 mL/day) to generate mild dehydration. Blood and urine samples were collected at baseline (B), day 4 and day 6. Blood pressure was measured at baseline and day 4. Renal function was assessed by plasma creatinine, plasma urea and creatinine clearance, and hydration status was determined by plasma osmolarity and water balance (i.e. water intake minus urine flow). Results Under basal conditions, all rats were hypertensive. The combination of trandolapril and furosemide significantly reduced the mean blood pressure on day 4 (p = 0.0066), while trandolapril or furosemide alone did not achieve these decreases. After four days of water restriction to 15 mL/day, all groups showed mild dehydration with a decrease in water balance and an increase in plasma osmolarity by. Plasma creatinine and plasma urea values were only increased on day 6 in the TW group (p = 0.0009 and p = 0.02, respectively). Creatinine clearance was also clearly reduced in the TW group (p = 0.0004). F+I and T+F groups showed slight decreases in creatinine clearance at day 6, as well as slight increases in plasma urea. However, these changes were not as pronounced as those observed in the TW group. Conclusion In our in vivo model of TW-AKI, mild dehydration cannot replace any of the TW drugs, although it appears that combination of F+I and T+F in dehydrated rats slightly alter plasma urea and creatinine clearance values at day 6, suggesting that this condition maintained over time might lead to the development of AKI. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union—NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Noelia Diaz-Morales is recipient of a Juan de la Cierva-Formación postdoctoral contract (FJC2020-043205-I) funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU/PRTR”. Eva M. Baranda-Alonso is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

#767 Utility of cystatin C as a predictor for postoperative acute kidney injury in non-cardiac surgeries [S1

Abstract Background and Aims Serum creatinine has been widely utilized to estimate glomerular filtration rate (eGFR), although various biomarkers have been developed to address its limitations. Among these biomarkers, the clinical use of Cystatin C is increasingly gaining recognition. However, there is a lack of evaluation regarding the utility of cystatin C in predicting the risk of postoperative acute kidney injury (PO-AKI) in non-cardiac surgeries. Method A retrospective cohort study was conducted on patients who underwent non-cardiac surgeries more than 1 hour from five departments (general surgery, neurosurgery, obstetrics and gynecology [OBGY], orthopedics, and urosurgery) at Chung-Ang University Hospital between 2018 and 2020. Patients with missing baseline information, including creatinine and cystatin C, and those without follow-up serum creatinine levels were excluded. PO-AKI was defined as KDIGO-AKI criteria occurring within 7 days after surgery. The estimated glomerular filtration rate (eGFR) was calculated from 2012 and 2021 chronic kidney disease-epidemiology collaboration (CKD-EPI) equations. Logistic regression was used to develop a prediction model, and C-statistics and the Delong test were used to compare the performance. Baseline comorbidities (diabetes mellitus [DM] and hypertension), laboratory findings (hypoalbuminemia [serum albumin &amp;lt;3.5 g/dL], anemia [hemoglobin &amp;lt;12 g/dL for female or &amp;lt;13 g/dL for male], and hyponatremia [sodium &amp;lt;135 mEq/L]), medication usage within 90 days of surgery (nonsteroidal anti-inflammatory drug and renin-angiotensin-system [RAS] blocker), and operation information (Anesthesia type, emergency operation, and operation duration) were adjusted. Results Overall, 339 patients were enrolled, with 49 patients (14.5%) developed PO-AKI. The median age was 73.0 [64.0; 80.0]; eGFR-Cr 86.4 [65.5; 99.1] mL/min/1.73 m2, eGFR-Cystatin C 70.0 [45.2; 92.7] mL/min/1.73 m2; eGFR-Cr/Cystatin C 77.2 [54.5; 100.5] mL/min/1.73 m2. Patients who developed AKI had a higher prevalence of diabetes (AKI 49.0%, no AKI 28.3%; p-value 0.006) and prescription of RAS blockers (AKI 63.3%, no AKI 34.5%; p-value &amp;lt;0.001), longer operation duration (AKI 63.3%, no AKI 34.5%; p-value &amp;lt;0.001), and lower eGFR of all types (AKI: eGFR-Cr 69.8, eGFR-Cystatin C 48.0, eGFR-Cr/Cystatin C 57.2; no-AKI: eGFR-Cr 88.0, eGFR-Cystatin C 74.0, eGFR-Cr/Cystatin C 80.5 mL/min/1.73 m2; p-values &amp;lt;0.001). No statistical differences were observed in other laboratory findings between the two groups (Table 1). The model with eGFR-Cystatin C demonstrated the highest area under the curve (AUC) among the three models (eGFR-Cr: AUC 0.78, 95% confidential interval [CI] 0.702‒0.857; eGFR-Cystatin C: AUC 0.81, 95% CI 0.735‒0.877; eGFR-Cr/Cystatin C: AUC 0.80, 95% CI 0.724‒0.871). Only the eGFR-Cystatin C-based model showed significant improvement in prediction compared to the eGFR-Cr-based model in the Delong test (eGFR-Cystatin C vs eGFR-Cr: p-value 0.033; eGFR-Cr/Cystatin C vs eGFR-Cr: p-value 0.055, Fig. 1). Conclusion Our findings suggest the potential usefulness of cystatin C in predicting the risk of PO-AKI non-cardiac surgery in addition to conventional PO-AKI risk factors. Further studies including larger and external cohorts, are needed for validation.