Anti-inflammatory Research Articles

A Retrospective Analysis of Disease Epidemiology, Comorbidity Burden, Treatment Patterns, and Healthcare Resource Utilization of Migraine in the United Arab Emirates.

Migraine is a recurrent, disabling neurological disorder with a substantial global disease burden. However, limited real-world data are available on the patient characteristics, treatment patterns, comorbidities, and economic burden of migraine in the United Arab Emirates (UAE). In this study, we evaluated the disease burden, comorbidities, treatment patterns, specialties involved in migraine diagnosis, and healthcare resource utilization (HCRU) and associated costs in patients with migraine in Dubai, UAE. A retrospective, secondary database cohort study was conducted from 01 January 2014 to 31 March 2022 using the Dubai Real-World Database. Patients aged ≥ 18years with at least one diagnosis claim for migraine with continuous enrollment during the study period were included. Patients were stratified into treatment sub-cohorts. Outcomes were evaluated in terms of clinical characteristics, comorbidities, specialists visited, treatment patterns, and HCRU. The study included 203,222 patients (mean age: 40years), with male predominance (55.4%). About 13.4% of patients had specific cardiovascular comorbidities. Frequently prescribed drug classes were nonsteroidal anti-inflammatory drugs (84.4%), triptans (29.8%), and beta-blockers (12.8%), while only 1.0% of patients with migraine were prescribed newer medications like calcitonin gene-related peptide antagonists. General medicine was the most frequently visited specialty on the index date (51.5%). The all-cause and migraine-specific median gross costs during the 12-month post-index period were US $1252.6 (2.4-564,740.7) and US $198.1 (0-168,903.3) respectively, with maximum contribution from inpatients. The contribution of migraine-specific median costs to all-cause median costs was highest for the diagnosis-related group (64.9%), followed by consumables (35.2%), medications (32.0%), procedures (24.5%), and services (24.5%). Migraine significantly impacts healthcare costs in the UAE. The role of newer therapies in migraine management should be explored to reduce the associated socioeconomic burden and improve patients' quality of life.

Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs

Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs. Materials and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs. Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2-type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes. Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects.

Cutting-Edge Developments and Patent Trends in Microspheres Drug Delivery: A Comprehensive Overview.

Microspheres have emerged as innovative drug delivery platforms with significant potential to improve the therapeutic efficacy of drugs with limited aqueous solubility and prolong their release. This abstract provides an overview of recent developments in microsphere research, highlighting key trends and innovative approaches. Recent studies have focused on various aspects of microspheres, including formulation techniques, materials selection, and their applications in drug delivery. Recent breakthroughs in polymer science have paved the way for the creation of innovative biodegradable and biocompatible materials for microsphere fabrication, improving drug encapsulation effectiveness and release dynamics. Notably, the integration of nanomaterials and functionalized polymers has enabled precise control over drug release rates and enhanced targeting capabilities. The utilization of microspheres for administering a diverse array of therapeutic substances, including anticancer drugs, anti-inflammatory agents, and peptides, has gained significant attention. These microspheres have demonstrated the potential to enhance drug stability, minimize dosing frequency and enhance patient adherence.

Phytoconstituents with cardioprotective properties: A pharmacological overview on their efficacy against myocardial infarction.

Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI-associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution. Synthetic drugs for the treatment of MI provide good chance of survival; however, the demand to search more safe, effective, and natural drugs is increasing. Plants provide fruitful sources for powerful antioxidant and anti-inflammatory agents for prevention and/or treatment of MI. However, many plant extracts lack exact information about their possible dosage, toxicity and drug interactions which may hinder their usefulness as potential treatment options. Phytoconstituents play cardioprotective role by either acting as a prophylactic or adjuvant therapy to the concurrently used synthetic drugs to decrease the dosage or relief the side effects of such drugs. This review highlights the role of different herbal formulations, examples of plant extracts and types of several isolated phytoconstituents (phenolic acids, flavonoids, stilbenes, alkaloids, phenyl propanoids) in the prevention of MI with reported activities. Moreover, their possible mechanisms of action are also discussed to guide future research for the development of safer substitutes to manage MI.

Functional Improvement at One Year in Fibrotic Interstitial Lung Diseases—Prognostic Value of Baseline Biomarkers and Anti-Inflammatory Therapies

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILDs) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for the improvement of lung function in patients with fibrotic ILDs. Methods: This registry-based study included 142 patients with fibrotic ILDs as defined by the presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as a relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 showed disease progression. Multivariate analyses found prognostic significance for age < 60 years (OR 5.4; 95%CI 1.9–15.4; p = 0.002), lactate dehydrogenase (LDH) >250 U/L (OR 2.5; 95%CI 1.1–5.8; p = 0.043) and blood monocyte count < 0.8 G/L (OR 3.5; 95%CI 1.1–11.3; p = 0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age < 60 years (OR 8.5 (95%CI 2.1–33.4; p = 0.002) as the only significant variable. Conclusion: Younger age, a higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Chronic liver disease and fibrosis: A review of emerging biomarkers and therapeutic targets

Chronic liver disease (CLD) and fibrosis represent a significant global health burden, driven by a range of etiologies including viral hepatitis, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD). These conditions often progress to cirrhosis, liver failure, and hepatocellular carcinoma (HCC), underscoring the urgent need for effective diagnostic and therapeutic strategies. Emerging biomarkers and therapeutic targets offer promising avenues for early diagnosis and intervention in CLD and fibrosis. Biomarkers are crucial for the early detection and monitoring of CLD and fibrosis, allowing for timely therapeutic intervention. Serum biomarkers such as liver enzymes (ALT, AST), bilirubin, and platelet count have traditionally been used, but they lack specificity and sensitivity. Recent advances have identified novel biomarkers with improved diagnostic performance. For instance, serum levels of fibrosis markers like hyaluronic acid, procollagen type III N-terminal peptide (P3NP), and tissue inhibitor of metalloproteinases-1 (TIMP-1) have shown potential in assessing liver fibrosis. Additionally, non-invasive imaging techniques such as transient elastography and magnetic resonance elastography provide quantitative measures of liver stiffness, correlating with fibrosis stage. The pathogenesis of liver fibrosis involves complex interactions between hepatocytes, hepatic stellate cells (HSCs), and the extracellular matrix (ECM). HSCs play a central role in fibrogenesis by transforming into myofibroblasts that secrete collagen and other ECM components. Targeting the activation and proliferation of HSCs has emerged as a promising therapeutic strategy. Small molecule inhibitors, such as those targeting the PDGF and TGF-? signaling pathways, have shown efficacy in preclinical models. Furthermore, antifibrotic agents like simtuzumab, an anti-LOXL2 monoclonal antibody, are being evaluated in clinical trials for their potential to halt or reverse fibrosis progression. Another promising approach involves the modulation of the gut-liver axis. Dysbiosis and increased intestinal permeability contribute to liver inflammation and fibrosis. Probiotics, prebiotics, and fecal microbiota transplantation (FMT) are being explored for their potential to restore gut homeostasis and mitigate liver injury. Additionally, the role of the immune system in fibrosis has gained attention, with immune checkpoint inhibitors and anti-inflammatory agents being investigated for their ability to modulate immune responses and reduce fibrosis. Keywords: Chronic Liver Disease, Fibrosis, Biomarkers, Therapeutic Targets.

Intermittent pulses of methylprednisolone with low-dose prednisone attenuate lupus symptoms in B6.MRL-Faslpr/J mice with fewer glucocorticoid side effects

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.

Attenuation of adjuvant-induced arthritis with carnosic acid by inhibiting mPGES-1, COX-2, and bone loss in male SD rats

Objective Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by joint swelling, cartilage erosion, and bone destruction. This study investigated the therapeutic efficacy of Carnosic acid (CA), a natural compound with anti-inflammatory and antioxidant properties, in an adjuvant-induced arthritis model. Methods Paw swelling and arthritis index were measured. Oxidative stress markers, including lipid peroxidation and antioxidant enzyme levels, were assessed. Synovial tissue was analyzed for pro-inflammatory markers using real-time Q-PCR and Western blotting. The expression of mPGES-1 was determined by Western blotting. Peripheral neuropathic pain was assessed using cold and mechanical allodynia tests. Bone loss was quantitatively assessed through microcomputed tomography (μCT) scanning of femurs and X-ray radiography. Indomethacin-induced gastric ulcers were evaluated. Molecular docking studies were conducted to analyze the binding affinity of CA to mPGES-1. Results The CA treatment not only demonstrated a significant reduction in joint inflammation and paw swelling but also mitigated oxidative stress and improved the antioxidant defence system. CA inhibited microsomal prostaglandin E synthase-1 (mPGES-1) expression and the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS) and cyclooxygenases-2 (COX-2), thus attenuating the arthritis symptoms without severe gastrointestinal side effects. Additionally, it inhibited the expression of pro-inflammatory molecules such as iNOS and COX-2, contributing to the reduction of arthritis symptoms. Notably, CA treatment prevented the common side effects of traditional RA treatments like corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), including weight loss, bone degradation, and gastric ulcers. Conclusions These findings suggest that CA, through specific enzyme inhibition, offers a compelling alternative therapeutic approach for RA. Further research is warranted to explore the potential of CA in other arthritis models and its suitability for human RA treatment.

Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

Morpho-Functional Analyses Demonstrate That Tyrosol Rescues Dexamethasone-Induced Muscle Atrophy

Prolonged exposure to high dosages of dexamethasone, which is a synthetic glucocorticoid and a well-known anti-inflammatory drug, may lead to an increase in reactive oxygen species production, contributing to muscle wasting. The prevention of muscle atrophy by ingestion of functional foods is an attractive issue. In the last decade, natural antioxidant compounds have been increasingly investigated as promising molecules able to counteract oxidative-stress-induced muscle atrophy. Recently, we have demonstrated the antioxidant properties of two main olive oil polyphenols also known for their anticancer and anti-inflammatory activities in different cell models. Here, the preventive effect of tyrosol on dexamethasone-induced muscle atrophy has been investigated by means of morpho-functional approaches in C2C12 myotubes. Dexamethasone-treated cells showed a reduced fiber size when compared to control ones. While long and confluent myotubes could be observed in control samples, those exposed to dexamethasone appeared as immature syncytia. Dysfunctional mitochondria and the accumulation of autophagic vacuoles contributed to myotube degeneration and death. Tyrosol administration before glucocorticoid treatment prevented muscle wasting and rescued mitochondrial and lysosomal functionality. These findings demonstrate that tyrosol attenuates dexamethasone-induced myotube damage, and encourage the use of this natural molecule in preclinical and clinical studies and in synergy with other functional foods or physical activity with the aim to prevent muscle atrophy.

Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.

Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. Patients aged ≥ 18years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs[95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. Inthe All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36(0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). The use of bDMARDs was not a time-dependent risk factor for malignancy.

Prevalence and associated factors of postoperative suxamethonium-induced myalgia in surgical patients at Debre Tabor Comprehensive Specialized Hospital Ethiopia: a cross-sectional study

Suxamethonium is considered by many to be the best drug for providing ideal intubating conditions, short surgical procedures, and rapid sequence induction. However, its usefulness is limited by the frequent occurrence of adverse effects like postoperative myalgia. Therefore this study aimed to assess the prevalence and associated factors of postoperative suxamethonium-induced myalgia. An institutional-based cross-sectional study was conducted on 210 patients who underwent surgery with general anesthesia. The data was collected by using structured and pretested questionnaires and analyzed using SPSS version 20.0. Logistic regression was conducted to identify significant predictors based on a P-value of less than 0.05 with a 95% confidence level. Among 210 patients the prevalence of suxamethonium-induced postoperative myalgia in the first 48 h was 88 (41.9%). Patients having previous anesthesia and surgical exposure (AOR 5.29, 95% CI 1.86–15.05), patients having a co-existing disease (AOR 2.69, 95% CI 1.08–6.67), patients that had not taken premedication (analgesia) (AOR 4.64, 95% CI 1.69–12.74), anesthesia maintenance using halothane (AOR 4.5 95% CI 1.7–11.4) and relaxation maintained with suxamethonium (AOR 3.1, 95% CI 1.2–8.1) were significantly associated with the prevalence of postoperative myalgia. The magnitude of suxamethonium-induced postoperative myalgia was high. So it is better to do with preventive techniques. As much as possible it is better to avoid using suxamethonium and necessary to use better to Premedicate with nonsteroidal anti-inflammatory drugs and non-depolarizing neuromuscular medications.

Topical Non-Steroidal Anti-Inflammatory Drugs for Management of Pain after Photorefractive Keratectomy - a Systematic Review and Network Meta-Analysis.

Topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for Management of Pain in Patients After Photorefractive Keratectomy (PRK). Pain after PRK is a major concern for both patients and surgeons. While evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDS. The study was prospectively registered with PROSPERO (ID -CRD42023417651). A systematic search of electronic databases was done, for randomized control trials (RCTs) reporting topical NSAIDs' outcomes of corneal reepithelization, rescue analgesics intake, and pain in days 0-3 after PRK (POD0-3). Studies were graded for risk of bias. Data were extracted and Standardized Mean Differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which frequentist approach model was fitted. Transitivity was assessed using the net-split method. Treatment effectiveness was ranked using forest plots based on comparison to placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons. Out of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0 ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95%CI [-1.86, -0.52]), POD2 (P 0.882, SMD -1.05, 95%CI [-1.82, -0.27]), and POD3 (P 0.939, SMD -1.14, 95%CI [-2.1, -0.18]). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95%CI [-1.33, -0.27]), ketorolac, and diclofenac. Compared to placebo, reepithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95%CI [-1.38, -0.03]). Flurbiprofen was favorable in pain scores on typically postoperative painful days and reepithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAIDs effect sizes should be taken into consideration.

Effect of Specific Surface Area and Hydrophobicity of Electrospun Nanofibers on the Sustained Release Performance of Diclofenac Sodium.

Nanofibers produced by electrospinning are suitable options for slow-release materials. Diclofenac sodium (DS) is a nonsteroidal anti-inflammatory medication with a brief half-life that can serve as an effective sustained-release agent. This paper presents a novel method for producing DS-sustained release nanofibers by electrostatic spinning processes. During the preparation, the slow-release capabilities of biodegradable materials poly(lactic acid) (PLA) and polycaprolactone (PCL) are investigated. A composite drug-carrying scaffold is prepared to enhance the sustained-release performance. The sustained release ability is affected by the specific surface area of the nanofibers and the hydrophobicity of the polymer. The findings indicate that the composite nanofiber with a PLA/PCL ratio of 1:1 demonstrates the most effective sustained-release performance. The release rate is mostly influenced by the hydrophobicity of the polymer at this point. Sustained-release kinetic simulations were performed and revealed that the release of nanofibers follows a first-order release paradigm. This work presents a straightforward approach for creating a sustained-release formulation of DS.

Salicylate induces epithelial actin reorganization via activation of the AMP-activated protein kinase and promotes wound healing and contraction in mice

Wounds that occur in adults form scars due to fibrosis, whereas those in embryos regenerate. If wound healing in embryos is mimicked in adults, scarring can be reduced. We found that mouse fetuses could regenerate tissues up to embryonic day (E) 13, but visible scars remained thereafter. This regeneration pattern requires actin cable formation at the epithelial wound margin via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). Here, we investigated whether the AMPK-activating effect of salicylate, an anti-inflammatory drug, promotes regenerative wound healing. Salicylate administration resulted in actin cable formation and complete wound regeneration in E14 fetuses, in which scarring should have normally occurred, and promoted contraction of the panniculus carnosus muscle, resulting in complete wound regeneration. In vitro, salicylate further induced actin remodeling in mouse epidermal keratinocytes in a manner dependent on cell and substrate target-specific AMPK activation and subsequent regulation of Rac1 signaling. Furthermore, salicylate promoted epithelialization, enhanced panniculus carnosus muscle contraction, and inhibited scar formation in adult mice. Administration of salicylates to wounds immediately after injury may be a novel method for preventing scarring by promoting a wound healing pattern similar to that of embryonic wounds.

Pharmacological insights and role of bufalin (bufadienolides) in inflammation modulation: a narrative review.

Bufadienolides, specifically bufalin, have garnered attention for their potential therapeutic application in modulating inflammatory pathways. Bufalin is derived from toad venom and exhibits promising anti-inflammatory properties. Its anti-inflammatory effects have been demonstrated by influencing crucial signaling pathways like NF-B, MAPK, and JAK-STAT, resulting in the inhibition of pro-inflammatory substances likecytokines, chemokines, and adhesion molecules. Bufalin blocks inflammasome activation and reduces oxidative stress, hence increasing its anti-inflammatory properties. Bufalin has shown effectiveness in reducing inflammation-related diseases such as cancer, cardiovascular problems, and autoimmune ailments in preclinical investigations. Furthermore, producing new approaches of medication delivery and combining therapies with bufalin shows potential for improving its effectiveness and reducing adverse effects. This review explores the pharmacological effects and mechanistic approaches of bufalin as an anti-inflammatory agent, which further highlights its potential for therapy and offers the basis for further study on its therapeutic application in inflammation-related disorders.

Review of the recent advances of pyrazole derivatives as selective COX-2 inhibitors for treating inflammation.

Pyrazole heterocycle is regarded as an extremely significant agent for the therapy of inflammation. Celecoxib, lonazolac, deracoxib, and phenylbutazone are examples of commercially approved pyrazole drugs with COX-2 inhibitory potential for curing inflammation. There have been recently many reviews for the biological significance of pyrazole derivatives. This review talks about pyrazole derivatives with anti-inflammatory activity and also sheds the light on the recent updates on pyrazole research with an emphasis on some synthetic pathways utilized to construct this privileged scaffold and structure activity relationship that accounts for the anti-inflammatory activity in an attempt to pave the opportunity for medicinal chemists to develop novel anti-inflammatory agents with better COX-2 selectivity.

The Effect of Giving Mangrove Leaf Extract (Rhizophora apiculata) on the Healing of Burn Wounds in Male White Rats (Rattus novergicus) of the Sprague Dawley Strain

A burn wound is damage or loss of tissues caused by contact with a heat source and can be classified into four degrees: I, IIA, IIB, and III. Anti-inflammatory and antioxidant agents such as mangrove leaves can be applied to aid the healing process of burns. One alternative method is to use mangrove leaf extract. This study aims to understand the acceleration of burn healing by applying mangrove leaf extract (Rhizophora apiculata). This study was a true experimental study with a post-test-only control group design, divided into five groups: Knormal (without treatment), K+ (bioplacenton), P1 (20% extract), P2 (30% extract), and P3 (40% extract). Burn wounds were observed for 21 days and assessed with average wound shortening, healing time, and the Bates-Jensen wound assessment tool. Based on the results of statistical tests, it was found that the application of Rhizophora apiculata leaf extract affected the healing of burns in white rats, resulting in a reduction in the burn area (P Value: 0.001). The application of mangrove leaf extract had an effect on the healing time of burns in white rats (P Value: 0.001). An effective dose of mangrove leaf extract was a concentration of 40% for healing burns, a higher effectiveness in healing burns compared to the standard drug, bioplacenton. The administration of mangrove leaf extract positively affects the healing of burns in male white rats (Rattus novergicus) of the Sprague Dawley strain, especially with an extract concentration of 40%.

From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction

Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.

Drugs Effective for Nonsteroidal Anti-inflammatory Drugs or Aspirin-induced Small Bowel Injuries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The frequency of small bowel (SB) injuries has increased due to the increased use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. This study was a systematic review and meta-analysis to compare drugs effective for SB injuries caused by NSAIDs or aspirin use. We searched MEDLINE, Embase, and Cochrane registries for randomized controlled trials through February 2023. The extracted data included changes in the number of erosions or ulcers in the jejunum or ileum observed through capsule endoscopy in patients taking NSAIDs or aspirin and administration of various mucoprotectants. We investigated the therapeutic or preventive efficacy of these drugs. The methodological bias was evaluated using Risk of Bias 2.0. Eighteen randomized controlled trials of drugs effective for NSAIDs or aspirin-induced SB injuries were included and analyzed. The agents used to treat or prevent SB injuries were rebamipide, misoprostol, geranylgeranylacetone, and probiotics. In the meta-analysis, the mucoprotectants that showed a significant effect in treating NSAID users, who developed SB injuries, were misoprostol (mean difference: -9.88; 95% CI: -13.26 to -6.50). Meanwhile, the mucoprotectant that can prevent SB injuries caused by NSAIDs or aspirin in the general population was rebamipide (mean difference: -1.85; 95% CI: -2.74 to -0.96). Misoprostol was effective in treating SB injuries caused by NSAIDs or aspirin (CRD42023410946).