Anti-inflammatory Research Articles

Characterizing immune biomarkers and effector CD8+ T-cell exhaustion in pancreatic adenocarcinoma via single-cell RNA sequencing profiling

Aim: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality and is characterized by T-cell exhaustion, particularly in effector CD8+ T-cells. This exhaustion, driven by persistent immunosuppressive signals in the tumor microenvironment, impairs immune function and hinders effective immunotherapy. This study aimed to identify key exhaustion-related marker genes in CD8+ T-cells linked to PDAC and assess the potential of repurposing anti-inflammatory drugs to counteract T-cell exhaustion and enhance immune responses against PDAC. Methods: We employed a multi-omics approach, integrating single-cell RNA sequencing data with whole genome sequencing to identify dysregulated exhaustion-related immune markers in CD8+ T-cells in PDAC. We examined gene expression profiles and conducted functional enrichment analysis to evaluate their roles in immune exhaustion. We analyzed mutations in the shortlisted biomarkers from The Cancer Genome Atlas (TCGA) and performed in silico mutational analysis using Maestro to evaluate the impact of an IL7R mutation (K110N) on protein function. Virtual screening using a deep learning framework, GNINA, explored the inhibitory features of the anti-inflammatory drugs oxaprozin and celecoxib on IL7R. Results: Key dysregulated exhaustion-related immune markers were identified including PRF1, GZMA, CD8A, CD3D, NKG7, IL7R, and IL2RG. Pathway enrichment analysis indicated significant involvement in T-cell receptor signaling, Th1 and Th2 differentiation, and Th17 differentiation pathways, correlating with reported poor survival outcomes in PDAC patients. Mutational analysis of IL7R revealed a likely pathogenic mutation (K110N) located in the IL-7Ralpha fibronectin type III domain. Drug repurposing of oxaprozin and celecoxib showed favorable binding interactions with both wild and mutant IL7R proteins. Conclusions: The K110N mutation, despite not causing significant structural changes, may impact T-cell and B-cell homeostasis and development. Our findings suggest that oxaprozin and celecoxib could effectively inhibit T-cell exhaustion through favorable interactions with IL7R. Further clinical studies are necessary to validate the therapeutic potential of these anti-inflammatory drugs in enhancing immune responses in pancreatic cancer.

Enhanced Corneal Repair with Hyaluronic Acid/Proanthocyanidins Nanoparticles.

This study investigates the therapeutic potential of hyaluronic acid/proanthocyanidin (HA/PAC) nanoparticles in treating alkali-induced corneal burns. Alkali burns are common ocular emergencies that can lead to severe vision impairment if not promptly and properly treated. The low water solubility of proanthocyanidins (PACs), which are potent antioxidant and anti-inflammatory agents, limits their bioavailability and therapeutic efficacy. To overcome this, hyaluronic acid (HA) was utilized as a carrier to form HA/PAC nanoparticles, enhancing PAC's solubility and bioavailability. The HA/PAC nanoparticles were characterized for morphology, granulometric distribution, hemolysis, and cytotoxicity, demonstrating high blood compatibility and noncytotoxicity. The in vitro antioxidant and anti-inflammatory capacities of HA/PAC were evaluated, showing enhanced activity compared to PAC alone. In vivo studies on C57 mice confirmed the accelerated healing of corneal injuries and reduced corneal opacity with HA/PAC treatment. Histopathological analysis and cytokine quantification further supported the anti-inflammatory and proregenerative effects of HA/PAC, suggesting its potential as an effective treatment for corneal alkali burns.

Mitigation of Neuroinflammation and Oxidative Stress in Rotenone-Induced Parkinson Mouse Model through Liposomal Coenzyme-Q10 Intervention: A Comprehensive In-vivo Study.

Parkinson's disease (PD) stands as the sec most prevalent incapacitating neurodegenerative disorder characterized by deterioration of dopamine-producing neurons in the substantia nigra. Coenzyme Q10 (CoQ10) has garnered attention as a potential antioxidant, anti-inflammatory agent and enhancer of mitochondrial complex-I activity. This study aimed to examine and compare the effectiveness of liposomal and non-encapsulated CoQ10 in rotenone induced-PD mouse model over a 21-day treatment duration. 30 mice were divided into 5 equal groups: Group I (mice receiving normal saline), Group II (rotenone was administered to mice), Group III (standard CoQ10 was given to mice), Group IV (mice were treated with non-encapsulated CoQ10) and Group V (mice were treated with CoQ10 Liposomes). Motor performance, the preservation of dopaminergic neurons, levels of neuroinflammation, oxidative stress, neurotransmitter levels, RT-qPCR analysis of PD-linked genes and histopathology were evaluated. The Liposomal CoQ10 group exhibited superior outcomes in behavioral tests such as reduced anxiety in the open field test, enhanced balance and coordination in beam balance test and improved cognitive performance in Y-maze test. Liposomal Coenzyme Q10 displayed pronounced antioxidative effects, evidenced by a significant (p < 0.001) increase in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities. In contrast, the non-encapsulated CoQ10 group showed a delayed response in mitigating the inflammation and oxidative stress. CoQ10 Liposomes demonstrated superior efficacy (p < 0.0001) in restoring dopamine and noradrenaline levels, reducing acetylcholinesterase activity, and downregulating Synuclein Alpha (SNCA) gene expression (0.722-fold change) compared to oral CoQ10, highlighting its potential in suppressing PD symptoms. The results of this study indicated that the liposomal CoQ10 effectively averted motor impairments, memory lapses, oxidative stress, as well as neuroinflammation triggered by rotenone.

Insilico and Invivo protective effect of biochanin-A mitigating doxorubicin- induced cognitive deficits and neuroinflammation: Insights to the role of p-Tau and miR-132.

Doxorubicin (DOX)-induced chemobrain has been reported in several studies. Its main culprit is the induction of massive amounts of reactive oxygen species (ROS), hence triggering damage to brain tissues and thus leading to neuroinflammation. Biochanin A (BIO-A) is known to be an antioxidant, anti-inflammatory, and neuroprotective agent. An insilico study was designed to examine the potential neuroprotective effect of BIO-A. An invivo study was used to evaluate the modulatory effect of BIO-A on cognitive impairment engendered by DOX. The insilico investigation proved the putative neuroprotective effect of BIO-A. In the invivo study, BIO-A treatment counteracted DOX-induced memory deficits, as evidenced by improved spatial memory in rats compared to the DOX-only group. BIO-A also reversed DOX-triggered hippocampal neurodegeneration and neuroinflammation, supported by a significant decrease in tissue contents of NF-κB (p65) by 32% and NLRP3 by 36% versus the DOX-only group. BIO-A also abrogated DOX-induced neurodegneration, as evidenced by increasing SIRT1 content by 2-fold and BDNF content by 2-fold versus the DOX-only group in hippocampal tissues. In addition, BIO-A ameliorated DOX-augmented apoptosis in the hippocampus, as evidenced by lowering caspase-3 content in the hippocampus by 26% versus the DOX-only group. Regarding tauopathy, BIO-A reversed DOX-increased tauopathy by 35% versus the DOX-only group. The neuroprotectant miR-132 was increased by BIO-A in hippocampal tissues by 4-fold, contrary to the DOX-only group. Thus, BIO-A treatment modulated DOX-induced behavioral, histological, and molecular changes in the hippocampi of rats. Further studies are recommended to evaluate BIO-A in early clinical trials for the purpose of protection against chemobrain in cancer patients.

Lipoxin A4 (LXA4) as a Potential Drug for Diabetic Retinopathy

The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)—factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR.

Biochemical strategy-based hybrid hydrogel dressing-mediated in situ synthesis of selenoproteins for DFU immunity-microbiota homeostasis regulation.

Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects. Specifically, Zero-valent selenium nanoparticles are synthesized and encapsulated into the alginate-polyacrylamide interpenetrating hydrogel networks, during which trehalose is adopted to modify the network defects. Besides, as an anti-adhesion agent, trehalose has shown the ability to prevent immune degradation by reducing bacteria binding to HUVECs. The obtained hybrid hydrogel dressing serves as a physical barrier against microbiome invasion, further regulates the composition of the wound microbiome to restore microbial immune homeostasis at the wound site, and cooperatively relieves DFU-associated symptoms. Meanwhile, the hydrogel dressing can synthesize selenoproteins in situ based on biochemical strategies and significantly reduce the secretion of proinflammatory cytokines. The proposed biochemical strategy based on the hybrid hydrogel dressings can efficiently restore microbiota-immune homeostasis in the wounds, presenting a promising approach for DFU therapy in clinics.

Phillygenin: A Versatile Multi-Targeted Anti-inflammatory, Hepatoprotactive and Anticancer Agent

Phillygenin: A Versatile Multi-Targeted Anti-inflammatory, Hepatoprotactive and Anticancer Agent

Design and evaluation of novel selective BET BD2 inhibitors by combining QSAR, molecular docking and molecular dynamics simulation techniques.

Bromodomain and extra terminal domain (BET) proteins play important roles in biological processes such as cell proliferation, differentiation, and signaling, and are involved in the occurrence and development of many diseases, including cancer and inflammatory diseases. Selective inhibitors targeting the first bromodomain (BD1) or the second bromodomain (BD2) have triggered a new wave of research to produce more specific and safer drugs. In this study, 37 novel selective BET BD2 inhibitors with anti-inflammatory activity are selected to construct robust Topomer CoMFA (q2=0.689, r2=0.916) and HQSAR (q2=0.805, r2=0.906) models, and both models have good external prediction ability. Based on QSAR results and ZINC15 database screening, 23 new compounds with ideal inhibitory activity are successfully designed. The stability and feasibility of binding the newly designed compounds to the target protein are further verified by molecular docking and molecular dynamics simulation validation. In conclusion, this work not only provides a reliable QSAR model as a screening tool for future anti-inflammatory drug development, but also provides a theoretical basis for the design and modification of subsequent selective BET BD2 inhibitors.

The epidemiology and unmet need of migraine in five european countries: results from the national health and wellness survey

BackgroundDespite the high global prevalence, burden, and direct and indicated costs, migraines are often under-diagnosed and undertreated. Understanding the prevalence of migraine and unmet needs is crucial for improving diagnosis and treatment across Europe (EU) countries; however, real-world studies are limited.MethodsThis retrospective cross-sectional survey utilized weighted patient-reported data from the 2020 National Health and Wellness Survey (NHWS) in five EU (5EU) countries (France, Germany, United Kingdom [UK], Italy, and Spain). The survey included adults aged ≥ 18 years who self-reported experiencing migraines in the past 12 months and had a physician’s diagnosis. The survey assessed migraine prevalence by age and sex. Other measures included migraine characteristics, disability assessment, migraine frequency (monthly migraine days [MMDs] and monthly headache days [MHDs], menstrually-related migraine, treatment patterns, and provider characteristics.ResultsThe study included 7,311 respondents with diagnosed migraines, representing an estimated 30.5 million adults with a weighted prevalence of 11.5% in the 5EU. Spain had the highest prevalence (14.0%), followed by Italy, France, UK, and Germany. Migraine prevalence was highest in the age group of 30–39 years, and females had nearly twice the prevalence compared to males. About 56% of respondents reported disability due to migraines, with highest percentage reported in Germany (66.0%). About 46% of female respondents reported experiencing menstrually-related migraines. One-fourth of the study respondents reported > 4 MMDs and 56.2% reported > 4 MHD. Current treatment patterns revealed that 79.7% of respondents were receiving some form of migraine treatment, with non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and triptans being the most commonly reported prescription medications. Primary care physicians (PCPs) were the most common providers diagnosing migraines, followed by neurologists.ConclusionsIn the 5EU, one-fourth of diagnosed respondents reported > 4 MMDs, and 56.2% reported > 4 MHDs. Nearly half of females experienced menstrually-related migraines. Although most patients reported taking medication for migraine, severe disability and medication overuse were observed. PCPs were the main treatment providers, highlighting the need for improved expertise and referrals to specialists. Further research is required for a better understanding of the disparities between migraine frequency and treatment approaches.

Phytochemical Composition, Medicinal Applications, and Pharmacological Insights: A Comparative Review of Rauvolfia serpentina and Rauvolfia tetraphylla

Aims: This review article aims to compare the phytochemical profile, therapeutic potential and pharmacological activities of Rauvolfia serpentina and Rauvolfia tetraphylla. Scope of Review: Review data from published literature and assess about phytochemicals, therapeutic applications and efficacy of Rauvolfia serpentina and Rauvolfia tetraphylla against microorganisms and inflammation comparatively. Methodology: Research papers and review articles on Rauvolfia serpentina and Rauvolfia tetraphylla were collected and analyzed about phytochemicals, medicinal uses, antibacterial and inflammatory properties. Summary of Findings: Rauvolfia serpentina and Rauvolfia tetraphylla have many similarities in its phytochemistry such as alkaloids like Reserpine, Ajmaline. They have been used to treat similar diseases and illness conditions like hypertension, psychotic disorders and snake bites. Conclusion: According to the findings, due to endangered status of Rauvolfia serpentina, Rauvolfia tetraphylla can be used as an ideal substitute and can be used for developing novel antimicrobial and anti-inflammatory drugs with mild side effects. Further investigations are necessary to determine their efficacy.

Natural Cyclic Peptides: Synthetic Strategies and Biomedical Applications.

Natural cyclic peptides, a diverse class of bioactive compounds, have been isolated from various natural sources and are renowned for their extensive structural variability and broad spectrum of medicinal properties. Over 40 cyclic peptides or their derivatives are currently approved as medicines, underscoring their significant therapeutic potential. These compounds are employed in diverse roles, including antibiotics, antifungals, antiparasitics, immune modulators, and anti-inflammatory agents. Their unique ability to combine high specificity with desirable pharmacokinetic properties makes them valuable tools in addressing unmet medical needs, such as combating drug-resistant pathogens and targeting challenging biological pathways. Due to the typically low concentrations of cyclic peptides in nature, effective synthetic strategies are indispensable for their acquisition, characterization, and biological evaluation. Cyclization, a critical step in their synthesis, enhances metabolic stability, bioavailability, and receptor binding affinity. Advances in synthetic methodologies-such as solid-phase peptide synthesis (SPPS), chemoenzymatic approaches, and orthogonal protection strategies-have transformed cyclic peptide production, enabling greater structural complexity and precision. This review compiles recent progress in the total synthesis and biological evaluation of natural cyclic peptides from 2017 onward, categorized by cyclization strategies: head-to-tail; head-to-side-chain; tail-to-side-chain; and side-chain-to-side-chain strategies. Each account includes retrosynthetic analyses, synthetic advancements, and biological data to illustrate their therapeutic relevance and innovative methodologies. Looking ahead, the future of cyclic peptides in drug discovery is bright. Emerging trends, including integrating computational tools for rational design, novel cyclization techniques to improve pharmacokinetic profiles, and interdisciplinary collaboration among chemists, biologists, and computational scientists, promise to expand the scope of cyclic peptide-based therapeutics. These advancements can potentially address complex diseases and advance the broader field of biological drug development.

Synthesis of Felbinac acid and Felbinac ester via PEPPSI palladium N-heterocyclic carbene catalytic system

Ethyl-4-biphenylacetate (Felbinac ester) and 4-biphenylacetic acid (Felbinac acid) are common active metabolites of non-steroidal anti-inflammatory drugs (NSAIDs) and are frequently used in the treatment of muscle inflammation and arthritis. The current studies synthesized Felbinacs via a Suzuki-Miyaura cross-coupling reaction mediated through PEPPSI-palladium N-heterocyclic carbene as a catalyst. The catalyst was synthesized through N-benzylation of benzimidazole followed by N-butylation of the resulting N-benzylbenzimidazole to yield the N-benzyl-N-butylbenzimidazolium bromide (the pre-carbene). The pre-carbene was then reacted with palladium bromide (PdBr2) in 3-methylpyridine, to produce the pre-catalyst (Pd-NHC-Py-Br2). The intermediates and the pre-catalyst were characterized using 1H and 13C NMR, FT-IR, and elemental analyses. The pre-catalyst was used to mediate the synthesis of 4-biphenylacetic acid (Felbinac acid) and 4-biphenylacetate (Felbinac ester) from the coupling reaction of Ethyl-4-bromophenyl acetate with phenylboronic acid. The Pd-NHC-Py-Br2 pre-catalyst demonstrated excellent air and moisture stability.

Pharmacological preventions and treatments for pericardial complications after open heart surgeries

BackgroundPericardial complications following cardiac surgery are common and debilitating, significantly impacting patients’ survival. We performed this network meta-analysis to identify the most effective and safest preventions and treatments for pericardial...

Enhanced delivery of anti-inflammatory therapeutics using pH-responsive histidine-modified poly-L-lysine on mesoporous silica nanoparticles

Mesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH-responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH2-Drug-PLL and MSN-NH2-Drug-PLL-His constructs. Characterization of these particles was conducted using Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH2-drug-PLL and MSN-NH2-drug-PLL-His was 237.10±6.56 nm and 234.03±14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL-His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems.

CHIT1 regulates the neuroinflammation and phagocytosis of microglia and suppresses Aβ plaque deposition in Alzheimer's disease.

Chitinase 1 (CHIT1), as a chitin-specific hydrolase, significantly influences the progression of Alzheimer's disease (AD) through microglia-associated inflammation and amyloid beta (Aβ) plaque accumulation. However, the precise mechanism of CHIT1 action in AD remains uncertain. The effects of CHIT1 on cerebral blood flow (CBF), hippocampal volume, and cognitive function were investigated in APP/PS1 mice. Protein alterations resulting from CHIT1 overexpression were analyzed using four-dimensional (4D) label-free quantitative (LFQ) protein spectrometry. Additionally, the influence of CHIT1 on microglial electrophysiology was assessed using patch clamp measurements, and its effects on neuroinflammation, phagocytosis, microglia migration, and neuronal apoptosis under AD-like conditions were examined using the cell lines N9, BV-2, and HT-22. CHIT1 ameliorated hippocampal atrophy, hypoperfusion, and cognitive function deficits in the APP/PS1 mouse. CHIT1 regulates microglial function and neuronal protection through its interactions in AD. Increased levels of CHIT1/IDH1 contributed to an anti-inflammatory phenotype in microglia via the Ca2+-activated K+ channel, enhanced microglial phagocytosis, and promoted Aβ clearance. Conversely, knocking down IDH1 reduced the secretion of anti-inflammatory agents and increased the production of inflammatory factors, as well as diminishing the expression of phagocytic factors and inhibiting Aβ endocytosis. Moreover, CHIT1 reduced neuronal apoptosis by diminishing the expression of apoptotic factors. However, IDH1 knockdown abrogated the protective effect of CHIT1 on neurons. CHIT1 exerts a protective role in AD pathogenesis through its interaction with IDH1. The CHIT1/IDH1 pathway promotes Aβ clearance via a shift in microglia toward an anti-inflammatory state and prevents neuronal apoptosis and dysfunction caused by Aβ toxicity. © 2025 The Pathological Society of Great Britain and Ireland.

DTPA and anti-inflammatory drug associations to alleviate Pu-induced response of macrophages in vitro.

Internal contamination by inhalation of plutonium poorly soluble compounds leads to their long time retention in alveolar macrophages inducing delayed pathology development. As previous studies highlighted co-localization of retained Pu and inflammatory lesions, this study was designed to assess the combined effect of the reference treatment (DTPA) and anti-inflammatory drugs on Pu-induced early response of macrophages in vitro. Pu colloids, mimicking poorly soluble Pu, were characterized using filtration and solid-state nuclear track detectors CR39. Their bioavailability was determined using a biphasic acellular model. Treatment effects on Pu dissolution and release as well as on Pu-induced pro-inflammatory response were assessed over 7 days on macrophage-like cells. DTPA treatment, associated or not with anti-inflammatory drug, increased Pu dissolution and release from contaminated THP-1 differentiated cells after 7 days. Significant decreases in Pu-induced IL-8 and MCP-1 secretions were also observed with anti-inflammatory treatment associated or not with DTPA. This study highlighted the ability of DTPA to partially dissolve a poorly soluble form of Pu as well as the ability of anti-inflammatory drugs to modulate Pu-induced pro-inflammatory response in macrophage-like cells. These treatments seem a promising strategy to improve the clinical management of Pu pulmonary contaminations and to limit delayed pulmonary pathology occurrence.

Synthesis of trans-Fused 3,6-Anhydro Hexofuranose Frameworks via Catalytic Hydrogenolysis Triggered Debenzylative Intramolecular Acetalation.

Presented herein is the chemical construction of unprecedented 3,4-trans-3,6-anhydro hexofuranose frameworks. The disfavored 3,6-anhydro hexofuranosides wereeffectively established by Pd-catalyzed debenzylative intramolecular acetalation for the first time. The critical roles of benzyl protection and Pd as catalyst were demonstrated. Various 3,4-trans-3,6-anhydro sugars including sauropunol E was first obtained in satisfactory yields. Pharmaceutical investigation of the sauropunol E and its analogues revealed their potential application as anti-inflammatory agents.

Acute idiopathic scrotal edema (AISE): A case report in Al-Ahsa, Saudi Arabia

Introduction: Acute idiopathic scrotal edema (AISE) is a rare, self-limiting condition of uncertain etiology, predominantly affecting children. It is characterized by sudden scrotal swelling and erythema without involvement of the testes or paratesticular structures. While benign, it can mimic more severe conditions like testicular torsion, requiring careful differentiation to avoid unnecessary surgical interventions. Case Report: We report the case of an 8-year-old boy in Saudi Arabia who presented with acute onset bilateral scrotal swelling, mild erythema, and tenderness, predominantly on the right side. There were no associated fever, trauma, or urinary symptoms. A similar episode two weeks earlier was resolved without medical intervention. Examination revealed generalized scrotal swelling with skin thickening, palpable testicles with normal position and size, and intact cremasteric reflexes. Laboratory results were unremarkable except for mild leukocytosis. Doppler ultrasound showed preserved vascularity of both testicles with characteristic edematous scrotal wall thickening and the “fountain sign,” confirming the diagnosis of AISE. Management and outcome: The patient was managed conservatively with non-steroidal anti-inflammatory drugs (NSAIDs) and intravenous (IV) ceftazidime. The symptoms resolved completely within 48 hours, and he was discharged in good condition with a short course of oral antibiotics. A two-week follow-up showed no recurrence or residual symptoms. Conclusion: This case underscores the importance of recognizing AISE in pediatric acute scrotum presentations to avoid unnecessary surgery. Clinical evaluation and Doppler ultrasound, highlighting the “fountain sign,” are pivotal for diagnosis. Conservative treatment ensures a rapid and favorable outcome, as demonstrated in this case.

Non-Steroidal Anti-Inflammatory Drugs Consumption and Awareness About Risks During Pregnancy In AL-Bayda City, Libya

Non-steroidal anti-inflammatory drugs are one of the most common prescribed medications for relieving pain, fever, and inflammation. Most NSAIDs are available without a prescription, and they often consumed by pregnant women for short periods of time to treat mild pain. However, these drugs can cause substantial teratogenic effects. NSAIDs such as aspirin, diclofenac sodium and ibuprofen might cause oligohydramnios (low amniotic fluid) or prenatal renal abnormalities if taken in the late second half of pregnancy. The US Food and Drug Administration (FDA) announced that taking NSAIDs in the period from the fifth month of pregnancy to delivery is not safe. This research was conducted to explore pregnant women's knowledge about NSAIDs during gestation period as well as consumption patterns. This study was conducted during the period from 10/2/2022 to 10/3/2022 in private clinics in Al-Bayda, Al-Quba cities as well as Al -Thawra hospital targeting 250 pregnant women who asked gently to fill in a printed questionnaire. The questionnaire has a variety of questions regarding age, consumption of NSAIDs during pregnancy and awareness about the benefits and risks of these drugs. Our study indicated that 55.6% of the pregnant women were in the range of twenty-two to twenty-nine years old. Half of pregnant women (50%) did consume painkillers (NSAIDs). Aspirin was the most common drug (55%). Forty-five out of 125 were consuming these drugs without prescription (36%). The common reason for consuming NSAIDs was varicose veins (31%). 30.4% of pregnant women had a miscarriage. Poor fetal growth was the most common cause of miscarriage among 29% of participants. Sixty-five percent of the participants knew that using this kind of drugs in the last month of pregnancy affect their health negatively. Only 4% of them had miscarriage due to consumption of NSAIDs. Pain management noticed in 90% of pregnant women. Awareness about the positive and negative effects of NSAIDs was noticed in 55% of the participants. In conclusion, despite the fact which is consumption of NSAIDs throughout pregnancy has undesirable effects on pregnant women and fetus, these drugs are widely prescribed by doctors to pregnant women. NSAIDs should not be prescribed during pregnancy unless mother's outcomes exceed the possible fetal adverse effects. Our research found no significant relation between NSAIDs consumption in the period of pregnancy and miscarriage. Although our results were satisfied, concentrated education programs are needed to spread knowledge in our society and another research must be conducted on a large sample size to investigate the differences among this study with the current research.

Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis.

The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have long remained unclear, recent studies have clarified the involvement of cholesterol crystals in inflammatory responses. Cholesterol crystals activate the NLRP3 inflammasome, a molecular complex involved in the innate immune system. Activation of NLRP3 inflammasomes in macrophages cause pyroptosis, which is accompanied by the release of inflammatory cytokines such as IL-1β and IL-1α. Furthermore, NLRP3 inflammasome activation drives neutrophil infiltration into atherosclerotic plaques. Cholesterol crystals trigger NETosis against infiltrated neutrophils, a form of cell death characterized by the formation of neutrophil extracellular traps (NETs), which, in turn, prime macrophages to enhance inflammasome-mediated inflammatory responses. Colchicine, an anti-inflammatory drug effective in cardiovascular disease, is expected to inhibit cholesterol crystal-induced NLRP3 inflammasome activation and neutrophil infiltration. In this review, we illustrate the reinforcing cycle of inflammation that is amplified by inflammasome activation and NETosis.