Anti-inflammatory Research Articles

Optimizing NSAID Therapy in Elderly with Osteoarthritis: A Case Study from a Primary Care Setting in Indonesia

Osteoarthritis (OA) is a degenerative disease often found in the elderly population. This disease is characterized by joint cartilage damage that causes pain and disability. Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the commonly used pharmacological therapies to manage pain in OA patients. However, the use of NSAIDs in the elderly requires special attention due to the risk of side effects, including gastrointestinal, cardiovascular and renal disorders. This study aimed to assess the pattern of NSAID use in elderly OA patients at the Lasi Community Health Center. This study used a descriptive observational method with prospective data from 111 patients during March-May 2019. The results showed that ibuprofen was the most commonly used NSAID (19.8%), followed by diclofenac (10.8%). Most patients received doses according to standard therapy. However, there were some cases of mild side effects such as dyspepsia (3.6%) and constipation (2.7%). This study emphasizes the importance of close monitoring of NSAID use in the elderly to optimize therapy and minimize the risk of side effects.

Current practices of pain assessment and analgesic use in laboratory mice: A 2022 FELASA Working Group survey.

Assessing and alleviating pain in animals involved in research is critically important. However, the effective implementation of pain management depends on the knowledge and attitudes of the personnel involved. Following a Federation of European Laboratory Animal Science Associations 'Pain in Mice' working group initiative, a questionnaire to survey current practices concerning analgesic use in laboratory mice was distributed to several professional groups in the field of laboratory animal science. Besides demographic data, attitudes to pain and analgesia and sources of information and advice on pain management were assessed. Data were gathered and analysed through an e-survey provider. Most respondents (N = 222) were from Europe (90%). Analgesics were administered to murine surgical models by 92% of respondents in most cases and by 66% to all mice undergoing surgery. Most respondents used multimodal analgesic regimens (69%). For non-surgical models, 34% of respondents provided analgesics. The most commonly administered classes of analgesics were opioids (mostly buprenorphine) and non-steroidal anti-inflammatory drugs (mostly meloxicam and carprofen). A wide range of dose rates of meloxicam and carprofen was reported. Local anaesthetics were also widely used in surgical models (mostly lidocaine). Pain assessment was undertaken by most respondents (98%). In conclusion, most respondents provided analgesics to mice undergoing surgery and used analgesics in some non-surgical models. A considerable variation in the dose range used and the timing of administration of analgesics likely reflects both a lack of data and variation in pain assessment methodologies.

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration

BackgroundThe retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration.MethodsLD was induced by exposing mice to 4000 lx of light for 2–4 hours (h). IBU (100 or 200 mg/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). Cell death genes were analyzed at 24 and 72 h after LD using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of key necroptosis genes were assessed by immunohistochemistry.ResultsRetinal outer nuclear layer (ONL) thickness in vehicle-injected LD animals was 8.7 ± 0.6% of retinas without LD (p < 0.0001). In IBU 200 mg/kg treated mice, central ONL thickness was 74.9 ± 7.7% of untreated retinas (p < 0.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hour after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1B), and C-C motif chemokine ligand 2 (Ccl2) increased by 10-, 17-, and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including Ripk3 and Mlkl, were upregulated in LD vehicle-treated mice, but dramatically reduced to near no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12 h after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas.ConclusionsSystemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.

Phyto-Fingerprinting of Putranjiva roxburghii Wall. Leaf Extract and its In Vitro Anti-Inflammatory Activity.

Putranjiva roxburghii is an important medicinal plant utilized for remedy of female reproductive ailments. Its seed extract is being used as a uterine health booster due to the presence of several pharmaceutically important phytochemicals. However, the presence of phytochemicals in its leaf is still unexplored. The present study was designed to explore phytochemical finger printing and assessment of anti-oxidant and anti-inflammatory activities of hydroalcoholic leaf extract of P. roxburghii (HALEPR). The qualitative, quantitative phytochemical of flavonoid, phenol and HRA-MS analysis of HALEPR carried out along with antioxidant and in vitro membrane stabilization and protein denaturation assay of anti-inflammatory activity were have been analyzed. Results of qualitative phytochemical screening of HALEPR denotes the existence of phenol, flavonoids, alkaloids, coumarins, steroids, saponins, tannins, anthroquinone and carbohydrates. The quantitative phytochemical of flavonoid and phenol was done which revealed the presents of total phenol and flavonoid. High resolution accurate-mass spectrometry (HRA-MS) study was also done for the identification of bioactive compounds from the HALEPR, which showed the presence of various phytochemicals such as luteolin 3'- (3″-acetylglucuronide), luteolin 4'-methyl ether 7-glucoside, quercetin-3β-D-glucoside, 8-hydroxyluteolin 4'-methyl ether 8-glucuronide, quercetin 3-xylosyl- (1- > 2) -rha mnosyl- (1- > 6) -glucoside, quercetin-3β-D-glucoside, myricetin 3- (3-6-diacetylglucosyl) - (1- > 4) - (2″,3″-diacetylrhamnoside), apigetrin, isorhamnetin, catechin 7,3'-Di-O-β-D glucopyranoside, luteolin 7-methylglucuronide, apigenin-8-C-α -l-arabinopyranoside, naringenin 7- O-β-D-glucoside 6″-acetate,ohobanin, shogaol, ginkgetin and amoritin. The HELPER is shown to have the presence of anti-oxidant and anti-inflammatory activities as demonstrated by DPPH (1, 1-diphenyl,2-picrylhydrazyl) and membrane lysis assays. Our findings reveal the presence of phytochemicals in HALEPR that have significant antioxidant and anti-inflammatory activity. The bioactivities were identified using chemical characterization like HRA/MS and biological assessments like anti-inflammatory and antioxidant assays. Future research may focus on isolating specific molecules, conducting in vivo tests, and creating HALEPR-based formulations for clinical application as anti-inflammatory drugs.

Recent advances in pharmacological treatments of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a severe complication of retinal detachment and trauma, posing significant challenges to surgical success and visual prognosis. Despite advancements in vitreoretinal surgery, PVR incidence remains unchanged, this review presents a synthesis of the principal clinical and preclinical research findings from recent years. Recent research has focused on anti-inflammatory, antiproliferative, and antifibrotic agents. Corticosteroids, such as triamcinolone and dexamethasone, show promise in reducing inflammation but have inconsistent results. Methotrexate and mitomycin C demonstrate efficacy in preclinical and select clinical scenarios. Anti-vascular endothelial growth factor agents and immunotherapies, like infliximab, have shown limited clinical benefits despite promising preclinical data. Novel approaches, including CB2 receptor agonists, exosome-based drug delivery, and nuclear factor kappa B pathway inhibitors, are gaining traction. Additionally, RNA-based and multitargeted therapies highlight the importance of addressing inflammation, fibrosis, and proliferation simultaneously. Effective management of PVR requires multifaceted therapies targeting its complex pathogenesis. While current treatments are limited, ongoing research in precision drug delivery and combination therapies offers hope for improved outcomes. Future strategies should focus on translating promising preclinical findings into robust clinical applications.

Regular Use of Oral Nonsteroidal Anti-inflammatory Drugs in a Population of Polish Seniors: Findings from the PolSenior2 Cross-Sectional Survey.

Older adults represent a growing proportion of the general population. Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a group of medicines that are both necessary, owing to their anti-inflammatory, analgesic, and cardioprotective abilities, and potentially harmful, owing to their side effects. This study provides a comprehensive analysis of NSAID usage patterns among Polish adults aged 60 years and older. It focused on the regular use (≥ three times per week) of two types of NSAIDs: acetylsalicylic acid (ASA) and non-ASA NSAIDs, examining consumption on the basis of age, sex, educational level, and place of residence. Data were collected from the PolSenior2 study, a national cross-sectional survey of 5987 Polish individuals aged 60-106 years, conducted from 2018 to 2019. The study found that 30.7% [95% confidence interval (CI) 28.8-32.7)]of Polish seniors regularly used NSAIDs, with 26.2% (95% CI 24.5-28.0) regularly using ASA, 6.3% (95% CI 5.3-7.2) regularly using non-ASA NSAIDs, and 1.9% (95% CI 1.4-2.3) reporting regular use of both. An age-related increase in regular NSAID use, including ASA, was observed. Women were more likely than men to use non-ASA NSAIDs regularly, whereas men in the 70-79 age group were more likely to use ASA. A lower level of education was associated with more frequent NSAID use. The findings have implications for healthcare practitioners and policymakers, emphasizing the need for careful management of NSAID use. The study contributes to a more nuanced understanding of NSAID usage and underscores the necessity for tailored healthcare strategies to ensure safe and effective medication use among older adults.

Antioxidant and anti-inflammatory function of walnut green husk aqueous extract (WNGH-AE) on human hepatocellular carcinoma cells (HepG2) treated with t-BHP.

Oxidative damage, oxidative inflammation, and a range of downstream diseases represent significant threats to human health. The application of natural antioxidants and anti-inflammatory agents can help prevent and mitigate these associated diseases. In this study, we aimed to investigate the effectiveness of walnut green husk (WNGH) as an antioxidant and anti-inflammatory agent in an in vitro setting. HepG2 cells were treated with tert-butyl hydroperoxide (t-BHP) to establish a cellular model of oxidative damage and inflammation. We assessed the biocompatibility of walnut green husk aqueous extract (WNGH-AE) on HepG2 cells using MTT and LDH assays (WNGH-AE concentration: 0.05, 0.1, 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg/mL). Additionally, we measured intracellular oxidative stress indicators, such as ROS and 8-OHdG, along with inflammatory factors TNF-α and IL-1β through ELISA to evaluate the antioxidant and anti-inflammatory capacity of WNGH-AE (concentration: 0.025, 0.05, 0.1 mg/mL) in HepG2 cells. We also determined the free radical scavenging capacity of various extracts of WNGH using DPPH and ·OH methods. The total phenols, total polysaccharides, and total flavonoids in WNGH-AE were analyzed using the Folin-Ciocalteu's reagent, the phenol-sulfuric acid method, and the spectrophotometry, respectively. The bioactive components of WNGH-AE were analyzed using LC-MS/MS. Our results demonstrated that WNGH-AE was highly biocompatible with HepG2 cells. The antioxidant effect of WNGH-AE involved the scavenging of intracellular ROS, while its anti-inflammatory effect was linked to the down-regulation of the NF-κB pathway. Compared to other extractants (ethyl acetate, n-butanol, 75% ethanol, and petroleum ether), WNGH-AE exhibited the strongest free radical scavenging ability. Through LC-MS/MS analysis, we identified 403 compounds in WNGH-AE, with gentisic acid being the most abundant and possessing high antioxidant capacity, suggesting it may be a key active component contributing to the antioxidant activity of WNGH-AE. In conclusion, our findings indicate that WNGH-AE is a natural, high-quality antioxidant and anti-inflammatory biomaterial deserving further research and development, with significant potential applications in healthcare. (311 words).

Screening and identification of host signaling pathways for alleviating influenza-induced production of pro-inflammatory cytokines, IP-10, IL-8, and MCP-1, using a U937 cell-based influenza model

Influenza virus infection initiates an exaggerated inflammatory response, which may culminate in a fatal cytokine storm characterized by the excessive production of pro-inflammatory cytokines. Prior research indicates that IP-10, IL-8, and MCP-1, primarily produced by monocytes and macrophages, play a crucial role in influenza-induced inflammation. The lung injury from influenza virus infection can be mitigated by suppressing or inhibiting these cytokines through knockout, knockdown, or targeted intervention approaches. To identify the key host signaling pathways responsible for producing pro-inflammatory cytokines, we utilized a U937 cell model that secretes IP-10, IL-8, and MCP-1 in response to influenza infection. This model has been previously validated in our laboratory as an appropriate system for screening anti-inflammatory agents and potential drug targets. We conducted a screening assay employing an inhibitor library consisting of 2,138 compounds that target various known pathways and host factors. Our findings indicated that inhibitors targeting protein tyrosine kinases and mitogen-activated protein kinases demonstrated superior efficacy in suppressing cytokine production induced by influenza A virus infection compared to inhibitors aimed at other host factors. Notably, a substantial proportion of the identified hits capable of inhibiting the expression of all three cytokines in the secondary screening were classified as tyrosine kinase inhibitors. Validation experiments further established that Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways, along with p38 MAPK and Raf–MEK–ERK pathways, are the principal regulators of pro-inflammatory cytokine expression in monocytes and macrophages. Moreover, our results suggest that TKIs present promising opportunities as novel therapeutic agents against influenza-induced pneumonia.

Management of intercostal artery pseudoaneurysm following posterior pedicle screw insertion: illustrative case.

Pedicle screw insertion in posterior spinal surgery can cause vascular injuries, including rare intercostal artery pseudoaneurysms, which are typically discovered incidentally during reimaging. Onyx embolization is an effective treatment for small artery pseudoaneurysms. A 36-year-old man who had initially presented with back pain that remained unresponsive to nonsteroidal anti-inflammatory drugs was diagnosed with a T7-8 sarcomatous lesion confirmed by magnetic resonance imaging and biopsy. He underwent a posterior resection and T5-10 stabilization with pedicle screws. After surgery, significant hemorrhage led to his transfer for digital subtraction angiography, which revealed a prominent vascular tumor blush and a pseudoaneurysm of the right T5 intercostal artery due to screw placement. The tumor and pseudoaneurysm were effectively embolized using superselective catheterization and Onyx. This report highlights the dangers of intercostal artery damage from posterior spinal screws, emphasizing the need for meticulous postoperative imaging. Onyx embolization is an effective treatment for such complications. https://thejns.org/doi/10.3171/CASE24291.

Effect of drug interactions with apixaban on clinical outcomes in cancer patients with venous thromboembolism

IntroductionIt is unclear how drug-interaction with apixaban influences recurrent venous thromboembolism (VTE) and bleedings in cancer patients.MethodsA post-hoc analysis of a single-arm interventional clinical trial on apixaban treatment of cancer patients with VTE to investigate whether the occurrence of any of the endpoints could be associated with the concurrent use of an interacting drug. Drugs taken by the patients during the trial period were categorized as either increasing bleeding risk, increasing thrombosis risk, both or neither.Results298 patients were divided into groups based on whether they used no interacting drugs (controls, n=74), drugs increasing bleeding risk (n=55), drugs increasing thrombosis risk (n=8), or both (n=161). Odds ratios (OR) were calculated for recurrent VTE, clinically relevant non-major bleeding (CRNMB), and major bleeding during the 36-month follow-up period. Each patient took a median of 13 different drugs over the study period. 67% of the patients used drugs expected to both increase bleeding and thrombosis. The use of fluconazole appeared associated with CRNMB (OR 3.6, 95% confidence interval (CI) 0.99-13), but not with major bleeding (OR 0.56, 95% CI 0.06 - 4.8). Non-steroid anti-inflammatory drugs were not associated with CRNMB (OR 1.0, 95% CI 0.25-4.1) or major bleedings (OR 0.72, 95% CI 0.14 - 3.6). Use of antiplatelet therapy was not associated with CRNMB (OR 0.75, 95% CI, 0.22 - 2.58) or major bleeding (OR 0.2, 95% CI, 0.02-1.6). There were no major bleedings in 23 patients using aprepitant nor in the 10 patients taking macrolides. We found no association between drugs and recurrent VTE, except that there were no recurrent VTE in 19 patients using bevacizumab.ConclusionsDespite the high number of drugs taken that could potentially interact with apixaban, none were found to clearly influence clinical outcomes, except that fluconazole may increase the risk of CRNMB.

Repurposing Diflunisal as an Anti-Virulence Agent Against Staphylococcus aureus

Abstract Infections refractory to standard antibiotic therapy are contributing to adverse treatment outcomes in patients suffering from deep-seated bacterial infections caused by increasingly resistant pathogens. Adjunctive strategies targeting bacterial virulence factors have been considered to supplement the host immune response in fighting the infection. Previous studies suggest that the FDA-approved anti-inflammatory drug diflunisal inhibits Staphylococcus aureus (SA) α-toxin expression by its interaction with the response regulator AgrA. We investigated the broader anti-virulence properties of diflunisal against pathogenic strains of SA and established proof-of-concept for its efficacy in blocking SA virulence. Our studies reveal that diflunisal inhibits α-toxin production, sensitizes SA to cationic antibiotics and human antimicrobial peptides, inhibits the production of the golden pigment staphyloxanthin, and reduces biofilm formation. Molecular docking simulations revealed potential interactions between diflunisal and AgrA binding sites. In addition, sequence alignment of the SA AgrA response regulator demonstrated similarities to other response regulators involved in controlling virulence factor expression. Appreciation of the antivirulence properties of diflunisal supports a therapeutic strategy distinct from structurally similar compounds, such as salicylic acid. The repurposing of diflunisal may mitigate disease severity and provide a unique adjunctive tool in the treatment of SA infection.

Kurarinone Mitigates LPS-Induced Inflammatory Osteolysis by Inhibiting Osteoclastogenesis Through the Reduction of ROS Levels and Suppression of the PI3K/AKT Signaling Pathway.

Inflammatory bone resorption represents a pathological condition marked by an increase in bone loss, commonly associated with chronic inflammatory conditions such as rheumatoid arthritis and periodontitis. Current therapies primarilyfocuson anti-inflammatory drugs and bisphosphonates; however, these treatments are limited due to side effects, inadequate efficacy, and unpredictable long-term complications. Kurarinone (KR), a bioactive compound isolated from the traditional Chinese herb Sophora flavescens, exhibits a range of biological activities, including anti-inflammatory, anticancer, and cardiovascular protective effects. To address the limitations of existing therapies and enhance drug utilization, this study explores the potential of KR as a therapeutic agent for inflammatory bone resorption and delineates its underlying mechanisms. In vitro experiments reveal that KR notably inhibits osteoclastogenesis and reduces the expression of osteoclastic markers. Additionally, KR decreases the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, while downregulating NADPH oxidase 1 (NOX1) and Kelch-like ECH-associated protein 1 (Keap1) to diminish ROS production. Furthermore, KR activates the nuclear factor erythroid 2-related factor 2 (Nrf2), which enhances the activity of heme oxygenase-1 (HO-1) and catalase (CAT), facilitating the clearance of excess ROS. The compound also hinders osteoclast formation and functionality by inhibiting the PI3K/AKT/GSK-3β signaling pathway. Lentiviral knockdown of CAT can partially reverse these effects of KR. Meanwhile, in vivo experiments indicate that KR effectively mitigates bone loss in an LPS-induced inflammatory bone resorption model. In summary, KR is a promising new star in breaking through the limitations of previous drugs and treating inflammatory bone resorption.

High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches

Chronic kidney disease (CKD) ultimately causes renal fibrosis and end-stage renal disease, thus seriously threatens human health. However, current medications for CKD and fibrosis are inefficient, which is often due to poor targeting capability to renal tubule. In this study, we discover that biomimetic high-density lipoprotein (bHDL) lipid nanoparticles possess excellent targeting ability to injured tubular epithelial cells by kidney injury molecule-1(KIM-1) mediated internalization. Thus, we co-load anti-inflammatory drug triptolide (TP) and anti-fibrotic drug nintedanib (BIBF) on bHDL nanoparticles to treat CKD. Based on the targeted delivery and mutual enhancement of the efficacy of co-delivered drugs, the bHDL-based system effectively reduces kidney injury and alleviates renal fibrosis in different CKD mouse models. The mechanistic study shows that BIBF and TP synergistically remodel the fibrotic niches by decreasing inflammatory cytokines, limiting immune cell infiltration and inhibiting the activation of myofibroblasts. The bHDL vehicle also possesses high manufacturability, good safety and adequately reduces the toxicity of TP. Thus, this system is promising for the treatment of CKD and bHDL has good potential for delivering agents to damaged renal tubular epithelial cells.

Experience of Two-Year Observation of а Patient with Dercum Disease During Methotrexate Therapy

Dercum disease, also known as painful lipomatosis, neurolipomatosis, Ander’s syndrome, is a rare illness. The main clinical manifestation of this disease is the presence of painful formations of subcutaneous tissue, localized in various parts of the body: on the limbs, trunk, buttocks. Possible etiological factors include genetic mutations, the presence of abnormal cellular proteins, endocrine disorders, changes in the nervous system. This disease is more common among women over 35 years old. Cases of Dercum disease in children and adolescents are rare. Patients with this disease are often overweight. There are 4 types of Dercum disease: generalized diffuse, generalized nodular, localized nodular, juxta-articular forms. In some cases, acute inflammatory markers increase: the erythrocyte sedimentation rate, C-reactive protein. A high level of tumor necrosis factor-α with a decrease over time was also noted in the presented clinical case, it requires further study of the prognostic capabilities as a marker of disease activity. Histological examination of subcutaneous elements did not reveal specific changes (the morphological picture corresponds to lipoma). Various methods of therapy are discussed in the literature, including liposuction, massage. Non-steroidal anti-inflammatory drugs, glucocorticoids, methotrexate also may be used. The clinical case presents a 42-year-old female patient with complaints of the presence of painful local nodular skin lesions of various sizes on the upper and lower extremities. We describe the early diagnosis of Dercum disease with differential diagnosis with panniculitis of other etiologies and the achievement of stable remission against the background of methotrexate therapy.

Cost-Effectiveness Analysis of Photobiomodulation After Third Molar Extraction for Pain Control

This study aims to evaluate the cost-effectiveness of photobiomodulation applied after third molar extraction. Materials and Methods: To evaluate cost-effectiveness, 15 studies were selected for a systematic review and 8 studies for a meta-analysis to determine the effectiveness of photobiomodulation after surgery. In the present study, as a measure of effectiveness, the pain scale (visual analog scale) was used. The laser value was extracted from the Unified Terminology of Supplementary Health (Brazilian Health System) according to the laser application protocol most common among the clinical trials selected for the meta-analysis. As for drugs, they were determined from those most used among the works included in the meta-analysis and within the protocols established by the Brazilian Ministry of Health. Results: The results of the overall analysis show a significant reduction in pain on the second day after surgery for the experimental group compared to the control (MD, −1.15; 95% CI, −1.73, −0.57). The control group has a lower cost and lower effectiveness, while laser treatment has a higher cost and higher effectiveness. Faced with this situation, the professional must clinically assess whether the cost of USD 34.62 for controlled pain intensity using the laser is worth the extra health benefit. Conclusions: Regarding the cost-effectiveness assessment, the control group has a lower cost and lower effectiveness, while laser treatment has a higher cost and higher effectiveness The decision of which treatment to choose must consider whether the cost of the therapeutic alternative outweighs the clinical gain caused by the treatment. Clinical Relevance: One of the most executed procedures in dentistry is the extraction of third molars. To reduce the negative post-surgical effects, anti-inflammatory drugs are prescribed, which can generate unwanted effects. Photobiomodulation is a technique to modulate inflammation, accelerate tissue repair, and reduce pain and discomfort in different clinical situations.

Navigating the Double- Edged Sword of Diclofenac: Pain Relief and Associated Cardiovascular Safety

Diclofenac sodium (DFS) is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) effective in managing pain and inflammation in patients with arthritis and musculoskeletal conditions. While DFS is known for its rapid analgesic effects and broad therapeutic indications, it also poses significant cardiovascular (CV) safety concerns. Research highlights that prolonged or high-dose use of diclofenac increases the risk of myocardial infarction, stroke, and thrombotic events. Despite clinical guidelines discouraging its use in patients with heart conditions, a large percentage of individuals continue its use after hospital discharge. This review explores the dual nature of diclofenac’s benefits for pain relief and its associated cardiovascular risks, discussing pharmacokinetics, therapeutic indications, adverse effects, and regulatory recommendations. Key words: Diclofenac, Nonsteroidal Anti-inflammatory Drugs (NSAIDs), Cardiovascular Risk, Pain Relief, COX-1 and COX-2 Inhibition, Myocardial Infarction, Prostaglandins, Thrombosis, Atherosclerosis

Genetic and species rearrangements in microbial consortia impact biodegradation potential.

Genomic reorganisation between species and horizontal gene transfer have been considered the most important mechanism of biological adaptation under selective pressure. Still, the impact of mobile genes in microbial ecology is far from being completely understood. Here we present the collection and characterisation of microbial consortia enriched from environments contaminated with emerging pollutants, such as non-steroidal anti-inflammatory drugs. We have obtained and further enriched two ibuprofen-degrading microbial consortia from two unrelated wastewater treatment plants. We have also studied their ability to degrade the drug and the dynamics of the reorganisations of the genetic information responsible for its biodegradation among the species within the consortium. Our results show that genomic reorganisation within microorganisms and species rearrangements occur rapidly and efficiently during the selection process, which may be facilitated by plasmids and/or transposable elements located within the sequences. We show the evolution of at least two different plasmid backbones on samples from different locations, showing rearrangements of genomic information, including genes encoding activities for IBU degradation. As a result, we found variations in the expression pattern of the consortia after evolution under selective pressure, as an adaptation process to the new conditions. This work provides evidence for changes in the metagenomes of microbial communities that allow adaptation under a selective constraint -ibuprofen as a sole carbon source- and represents a step forward in knowledge that can inspire future biotechnological developments for drug bioremediation.

Psoriasis-Arthritis: Update der EULAR-Empfehlungen

Objective: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. Methods: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. Results: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. Conclusion: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Chitosan and ibuprofen grafted electrospun polylactic acid/gelatin membrane mitigates inflammatory response.

Electrospun membranes with biomimetic fibrous structures and high specific surfaces benefit cell proliferation and tissue regeneration but are prone to cause chronic inflammation and foreign body response (FBR). To solve these problems, we herein report an approach to functionalize electrospun membranes with antibacterial and anti-inflammatory components to modulate inflammatory responses and improve implantation outcomes. Specifically, electrospun polylactic acid (PLA)/gelatin (Gel) fibers were grafted with chitosan (CS) and ibuprofen (IBU) via carbodiimide chemistry. Our results show that the surface modification strategy endows electrospun membranes with moderate antibacterial activities and sustained release of anti-inflammatory drugs. The electrospun PLA/Gel-CS-IBU membrane showed good antioxidant and anti-inflammatory activity as evidenced by suppressing M1 polarization and promoting M2 polarization of macrophages in vitro. Similarly, it induced significantly milder chronic inflammatory responses in vivo than unmodified electrospun membranes. Given the good anti-inflammatory and antibacterial effects, this strategy might improve the biological performance of electrospun membranes as implants in clinics.

Clinical features of inflammatory arthritis in daily practice-China's perspective.

This study aimed to analyze and compare the proportion of patients with different types of inflammatory arthritis and investigate the clinical characteristics, including symptoms and signs, medication choices, and disease activity, in the daily clinical practice of China. Patients with inflammatory arthritis were recruited from 16 Grade-A tertiary hospitals between August 2021 and April 2022. The medical profiles, encompassing sociodemographic characteristics, clinical and laboratory date, were collected. This study included 2,693 patients with arthritis, with rheumatoid arthritis (RA) accounting for the highest proportion (50.50%). Significant differences were observed in terms of age,gender, body mass index (BMI), disease duration, smoking and family history among patients with different types of inflammatory arthritis. Physical activity and cold exposure were identified as the main predisposing factors for RA, psoriatic arthritis (PsA), osteoarthritis (OA), and ankylosing spondylitis (AS), while alcohol consumption was the most common inducing factor for gout. Hypertension and hyperlipidemia were the primary concomitant diseases in RA, OA, and AS, whereas hyperuricemia and hypertension were mainly associated with gout, psoriasis and diabetes were the most common comorbidities in PsA. Peripheral joints were predominantly affected in PsA, RA, OA, and gout, while axial joints were mainly affected in AS. Methotrexate and leflunomide were the main therapeutic drugs for RA, while biologics were commonly prescribed for PsA and AS. OA and gout patients mainly utilized nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with different types of inflammatory arthritis exhibited varying predisposing factors, joint inflammation, concomitant diseases, and medication choices, highlighting the importance of individualized approaches in the clinic. Key Points • 2,693 patients classified and diagnosed with inflammatory arthritis were recruited in this study from 16 Grade-A tertiary hospitals in China between August 2021 and April 2022. • This study analyzed and compared the proportion of patients with different types of arthritis in routine clinical practice in China. • Joint inflammation, comorbidities, and medication choices were assessed among patients with the most common types of arthritis in this study. • This study also provided some epidemiologically relevant information about inflammatory arthritis patients in China.